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what is constipation? | Constipation is a condition in which fewer than three bowel movements a week occur or movements are hard, dry, and painful or difficult to pass. Constipation is a condition in which fewer than three bowel movements a week occur or movements are hard, dry, and painful or difficult to pass. Skip to main content U.S. Department of Health and Human Services | PROBIOTICS & CONSTIPATION. What Probiotic is good for constipation. Florastor is a good one for people with diarrhea. But the main ingredients in Florastor is for people with diarrhea compared to constipation. Florastor's main ingredient is Saccharomyes & Boulardi lyo. | eng_Latn | 22,600 |
does eating garlic make you bloated | Gas, bloating, intestinal cramps, and diarrhea are common effects of eating garlic, especially if you are sensitive to it. The supposed health benefits of garlic and the common myth that garlic is good for you does not apply if it makes you sick. | Fructans and Stomach Pain. If you are sensitive to fructans, eating garlic will cause an excessive fermentation of the fructans by the bacteria in your gastrointestinal tract. The excess gas produced by the fermentation of the fructans of garlic can result in bloating, flatulence and pain.There is no test to diagnose fructan intolerance, but keeping a food journal can help you identify which foods in your diet cause your stomach to hurt.he excess gas produced by the fermentation of the fructans of garlic can result in bloating, flatulence and pain. There is no test to diagnose fructan intolerance, but keeping a food journal can help you identify which foods in your diet cause your stomach to hurt. | eng_Latn | 22,601 |
symptoms of dairy intolerance | Intolerance to dairy foods can stem from a negative reaction to lactose or to milk proteins. Lactose intolerance is a digestive disorder in which you lack sufficient lactase, the enzyme that breaks down lactose in your gut.Symptoms of abdominal cramps, bloating, gas and diarrhea shortly after consuming milk products might indicate an intolerance to this milk sugar.ntolerance to dairy foods can stem from a negative reaction to lactose or to milk proteins. Lactose intolerance is a digestive disorder in which you lack sufficient lactase, the enzyme that breaks down lactose in your gut. | Lactose intolerance is a condition where an individual experiences stomach bloating and stomach ache after eating dairy items. Abdomen pain after eating can likewise develop due to the presence of gall stones. If you experience discomfort in the right side of the abdominal areas, then you most likely have the stones. | eng_Latn | 22,602 |
can you develop lactose intolerance suddenly | Itâs possible. Most people experience a gradual decline of lactase (the enzyme that helps your body digest milk products) activity as they age. If dairy isnât sitting with you as well as it used to, try this self-test: Stop consuming dairy products for five days, and on the sixth day, drink a glass of milk. If your symptoms resolve during the dairy-free days and return when dairy is reintroduced, you most likely have developed lactose intolerance. | Lactose intolerance is the inability to break down a type of natural sugar called lactose. Lactose is commonly found in dairy products, such as milk and yogurt.A person becomes lactose intolerant when his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose.When this happens, the undigested lactose moves into the large intestine. person becomes lactose intolerant when his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose. When this happens, the undigested lactose moves into the large intestine. | eng_Latn | 22,603 |
does overeating cause diarrhea | Many people with lactose intolerance can eat a small amount of lactose, but overeating ice cream, milk and other dairy products can cause abdominal cramping and diarrhea. To avoid this type of diarrhea, don't overindulge in dairy products. | Taking too much creatine at once, due to a combination of limited intestinal absorption in high doses and drawing water into the intestines, can cause diarrhea. Additionally, the water drawing properties can lead to an upset stomach or nausea. | eng_Latn | 22,604 |
does chocolate cause heartburn | My beloved chocolate gave me ulcers, heartburn and caused me to lose half my body weight. Sophie Jewett is a true chocoholic. As a child, she was so hooked on Dairy Milk she had to have a bar every day. She even decided to train as a chocolatier, opening her own business, York Cocoa House, last November. | CHOCOLATE, on the other hand, apparently becomes quite acidic after you eat it. The website below explains this, and also offers a BIG and interesting list on which foods turn which way during digestion. Hmmm... now I understand why, if I eat too much chocolate, my acid reflux often acts up and I get heartburn. | eng_Latn | 22,605 |
why does lactose cause gas | People with lactose intolerance do not produce enough of the lactase enzyme to break down lactose. Instead, undigested lactose sits in the gut and gets broken down by bacteria, causing gas, bloating, stomach cramps, and diarrhea. Lactose intolerance is fairly common and seems to affect guys and girls equally. | Dairy products: The sugar lactose in dairy foods is a common cause of gas, which can sometimes be an indication of lactose intolerance. This is a condition in which the lactose in milk and other dairy products canât be properly digested. People with lactose intolerance have difficulty digesting dairy products such as, | eng_Latn | 22,606 |
causes of developing lactose intolerance as an adult | Lactose intolerance occurs when the small intestine does not make enough of an enzyme called lactase. Your body needs lactase to break down, or digest, lactose. Lactose intolerance most commonly runs in families, and symptoms usually develop during the teen or adult years. Most people with this type of lactose intolerance can eat some milk or dairy products without problems. | Lactose intolerance is the inability of adults and children to digest lactose, a sugar found in milk and to a lesser extent dairy products, causing side effects.It is due to a lactase deficiency, or hypolactasia.actose intolerance is not an allergy, because it is not an immune response, but rather a sensitivity to dairy caused by lactase deficiency. Milk allergy, occurring in only 4% of the population, is a separate condition, with distinct symptoms that occur when the presence of milk proteins trigger an immune reaction. | eng_Latn | 22,607 |
can chocolate cause stomach upset | Dr. Rick, MD : Usually dark chocolate, in and of itself, will not cause burning of the stomach. Dr. Rick, MD : That being said, if you have some pre-existing stomach upset or stomach pathology, such as an ulcer, anything -- including dark chocolate -- can upset your stomach. Dr. Rick, MD : | Cocoa, in whatever form, isnât likely to cause constipation. The darker the chocolate, the higher the amount of natural cocoa fat it contains, and the less likely it is to cause constipation. Yes, you can eat rich, bittersweet dark chocolate without a fear of constipation. The lighter a chocolate, the more milk and sugar it will contain, making it more likely to cause constipation. A perfect answer for chocolate lovers | eng_Latn | 22,608 |
Prevent Gastrointestinal Stasis in Rabbits | Domestic rabbits are directly descended from wild rabbits, and because of this, they have specific feeding requirements due to the way their body digests foods. | Bloat in cattle is a serious problem--and a very old one--that is often associated with consumption of high quality feeds that are easily digestible and rapidly fermented in the rumen. ( | eng_Latn | 22,609 |
i always fart in class ,and my crush laffs at me and i dont like how do i preevent farting | Run around in the hallway OR walk past someone else and then blame it on them OR spray some perfume at the same time - Glo smells very strongly. | it could be the foods you are eating:\nmost veggies will give you gas along with most beans. If you are eating a high fiber diet that can also cause some gas.\n\nYou may want to try Bean-o to see if that works for you.\n\nIf not check with your MD. | eng_Latn | 22,610 |
what is excessive farting called | Flatulence is defined in the medical literature as flatus expelled through the anus or the quality or state of being flatulent, which is defined in turn as marked by or affected with gases generated in the intestine or stomach; likely to cause digestive flatulence.latulence is defined in the medical literature as flatus expelled through the anus or the quality or state of being flatulent, which is defined in turn as marked by or affected with gases generated in the intestine or stomach; likely to cause digestive flatulence. | While many people believe they pass gas too much and become worried, an abnormal quantity is VERY rare. Catapulting gaseous elements out of your orifices 13 to 21 times a day is average. Farting and burping even 30 times a day is, unfortunately for us, still a normal occurrence. | eng_Latn | 22,611 |
what causes hay belly in horses | Poor quality hay or grass can lead to hay belly in horses. The digestive system of your horse is made to extract nutrients from grass and hay. Horses donât have a way to break down fiber, however bacteria in their large intestine will ferment the hay or grass. | A rich diet fed infrequently or a sudden change to rich grass are the most common causes of gassy or spasmodic colic whereas impactions are usually caused by inactive horses on box rest and eating a straw bed. More severe forms of colic, such as a twisted or entrapped piece of intestine, are less predictable. There is not usually a clear cause and they are less likely to be caused by poor management. It was once thought that the act of a horse rolling causes the intestine to twist but that is now known to be wrong. | eng_Latn | 22,612 |
can baking soda cause constipation | Baking soda can be used as a laxative to combat indigestion and constipation, says EverydayRoots. In order to ingest the baking soda properly, dissolve a teaspoon of it in 1/4 cup of water. Drink the solution as soon as it is mixed to experience the bicarbonate's maximum effect. Continue Reading. | Baking soda is pure sodium bicarbonate. When baking soda is combined with moisture and an acidic ingredient (e.g., yogurt, chocolate, buttermilk, honey), the resulting chemical reaction produces bubbles of carbon dioxide that expand under oven temperatures, causing baked goods to expand or rise. | eng_Latn | 22,613 |
what causes blossom end rot on tomatoes | Blossom end rot is caused by the tomato plant not being able to get enough calcium to the developing fruit. It is not caused by a plant disease like a fungus or bacteria. Blossom end rot may also occur in peppers, melons, eggplants, squash and cucumbers. | If the scabs are on the blossom end of the fruit it is likely what is called blossom end rot (BER). BER is caused ultimately by the fruit not having enough calcium during it's development. The other component to BER is letting the soil dry out too far during a critical phase of fruit development. | eng_Latn | 22,614 |
can eating raw garlic give stomach pain | An article published in American Family Physician in July 2005 noted that eating raw garlic on an empty stomach is particularly likely to cause irritation to the digestive tract. Other symptoms that can result from eating too much raw garlic include vomiting and stomach pain.owever, raw garlic can also cause digestive problems, including bloating, for some people. | The reason why your stomach can hurt when eating garlic is because it is rich in fructans. Fructans is a compound commonly found in many foods, including fresh or cooked garlic as well as garlic powder and garlic salt. Fructans are made of a chain of fructose and are not digested in humans. | eng_Latn | 22,615 |
average human beings pass gas how many times in a day | The average person passes gas about 14 times a day. Also women fart as much as men. On average, a person produces about half a liter of fart gas per day, distributed over an average of about fourteen daily farts. Most people pass gas 14 times a day, and each person produces about half a liter of farts everyday. | Stomach gas buildup can be extremely discomforting and, sometimes, embarrassing. Having stomach gas is normal and healthy, as it is a byproduct of the human digestive system. On average, a person can pass anywhere from a pint to 2 quarts of gas per day. Most gas, trapped in the body, is expelled via burping. The rest is absorbed by the small intestine and released through the rectum. | eng_Latn | 22,616 |
what causes end rot on tomatoes | If you see a dark, rotting spot on the bottom of your tomatoes, itâs blossom-end rot. This problem, caused by a calcium deficiency, can be solved a few ways. When tomatoes, peppers, melons, and eggplant develop a sunken, rotten spot on the end of the fruit, the cause came long before you found the problem. Itâs called blossom end rot, and here is why it happens. Vegetables need calcium for healthy development. When tomatoes, peppers, melons, and eggplant canât get enough from the soil, the tissues on the blossom end of the fruit break down. | (Redirected from Blossom end rot) Calcium deficiency (blossom end rot) on a tomato. Calcium (Ca) deficiency is a plant disorder that can be caused by insufficient calcium in the growing medium, but is more frequently a product of low transpiration of the whole plant or more commonly the affected tissue. | eng_Latn | 22,617 |
can motility disorder cause small bowel obstruction | The causes of bowel motility disorders can vary â some may arise within the digestive tract, others may be arise from outside of the gut. Whatever the cause and wherever the origin of the problem, it ultimately leads to abnormal muscle contractions within the bowel wall. | Decreased gastrointestinal motility: Introduction. Decreased gastrointestinal motility: Decreased gastrointestinal motility is a lowered functioning of the gastrointestinal tract in which food is not digested and moved normally through the gastrointestinal tract.ome of the comorbid or associated medical symptoms for Decreased gastrointestinal motility may include these symptoms: 1 Nerve symptoms. 2 Sensory symptoms. 3 Abdominal symptoms. 4 Body symptoms. 5 Digestive symptoms. 6 Esophagus symptoms. 7 Muscle symptoms. | eng_Latn | 22,618 |
how to get rid of full feeling | For you I would say your fullness is caused by gas. Get some Gas X and take after you eat and see if it helps. My son gets what youdo and Gas X works great for him. For myself, the only way I can get the full feeling to go away is to drink 2-3 glasses of ice cold water. It washes the digested food from your stomach so you don't feel so full. As I said, I have had this 9 years and have tried everything and Gas X and lots of water are the only thing that helps me. | Re: How do I get rid of this full and bloated feeling? I swear every time I eat I feel like i'm going to blow up. I couldnt even finish a whole sandwhich yesterday. After I eat I immediately feel totally bloated and am burping and have major gas. My stomach feels like it has a water balloon in it. | eng_Latn | 22,619 |
how to get rid a bloated stomach | 1 Take Proper diet Diet plays the key role in controlling stomach bloating. 2 You should avoid such foods that you find hard to digest. 3 Avoid all kinds of fatty and greasy food which can causes gas buildup in your stomach such as fast foods or meal cooked in excess oil. | How to get rid of a bloated stomach instantly. It is not difficult to get rid of the gas and swelling, although it seems very difficult! You can easily get rid of it by simply following some better ways. Here are the Best ways to get rid of gas and bloating! 1.Peppermint tea. | eng_Latn | 22,620 |
stomach feels sensitive | A sensitive stomach is a term commonly used to describe a range of upper gastrointestinal symptoms, particularly in response to certain foods or situations. It is a non-specific term for any cause that may trigger the the onset or worsen symptoms like nausea, vomiting, indigestion, bloating, heartburn or excessive belching. | This should be coupled with good eating habits. Here are some foods that may help if you have a sensitive stomach: 1 Foods rich in carbohydrates such as rice are easily digested, yet not acid forming. A good combination of foods is starch- or protein-rich food and vegetables. | eng_Latn | 22,621 |
Background Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been reported to improve erectile function in patients with moderate-to-severe erectile dysfunction (ED) or even convert phosphodiesterase type 5 inhibitors nonresponders to responders. ED is highly prevalent in hypertensive patients. The effect of Li-ESWT on an animal model of hypertension-associated ED has not been reported. Aim To investigate the effect of Li-ESWT on hypertension-associated ED and provide plausible mechanisms of action of Li-ESWT on local mechanisms of penile erection. Methods Spontaneously hypertensive rats (SHRs) in the active group (n = 13) received Li-ESWT at energy flux density 0.06 mJ/mm2 (Aries; Dornier MedTech, Wessling, Germany) twice weekly for 6 weeks. The emitter was set to zero for SHRs in the sham group (n = 12). Erectile function was assessed 4 weeks post-treatment by monitoring intracavernosal pressure (ICP) in response to electrical stimulation of cavernous nerve before and after single dose of 0.3 mg/kg intravenous sildenafil. Cavernosal tissue was then evaluated for collagen/smooth muscle content, neuronal nitric oxide synthase (nNOS), and vascular endothelial factor (CD31) expression. Outcomes Erectile function was assessed with ICP, erectile tissue remodeling was studied by smooth muscle/collagen ratio, nNOS and CD31 were semiquantitatively evaluated on cavernosal sections. Results The improvement of ICP parameters was greater in Li-ESWT–treated rats compared with controls with and without sildenafil. Sildenafil led to 20% increase in area under the intracavernosal pressure curve measured during the entire response/mean arterial pressure at 10 Hz in ESWT_SHR + sildenafil compared with ESWT_SHR. The smooth muscle/collagen ratio increased 2.5-fold in Li-ESWT compared with sham. Expression of CD31 tended to be increased whereas nNOS was unchanged. Conclusions Li-ESWT by Aries may represent an effective noninvasive therapeutic alternative and a relevant add-on therapy to phosphodiesterase type 5 inhibitors for ED in hypertensive patients, and it is suggested that it acts via remodeling of the penile tissue and promoting cavernosal vascularization. Assaly R, Giuliano F, Clement P, et al. Extracorporeal Shock Waves Therapy Delivered by Aries Improves Erectile Dysfunction in Spontaneously Hypertensive Rats Through Penile Tissue Remodeling and Neovascularization. Sex Med 2019;XX:XXX–XXX | Shock waves (SW), defined as a sequence of single sonic pulses characterised by high peak pressure (100 MPa), a fast rise in pressure (< 10 ns) and a short lifecycle (10 � s), are conveyed by an appropriate generator to a specific target area at an energy density ranging from 0.03 to 0.11 mJ/mm 2 . Extracorporeal SW (ESW) therapy was first used on patients in 1980 to break up kidney stones. During the last ten years, this technique has been successfully employed in or- thopaedic diseases such as pseudoarthosis, tendinitis, calcarea of the shoulder, epicondylitis, plantar fasciitis and several inflammatory tendon diseases. In particular, treatment of the tendon and muscle tissues was found to induce a long-time tissue regeneration effect in addition to having a more immediate anthalgic and anti-inflammatory outcome. In keeping with this, an increase in neoangiogenesis in the tendons of dogs was observed after 4-8 weeks of ESW treatment. Fur- thermore, clinical observations indicate an immediate increase in blood flow around the treated area. Nevertheless, the biochemical mechanisms underlying these effects have yet to be fully elucidated. In the present review, we briefly detail the physical properties of ESW and clinical cases treated with this therapy. We then go on to describe the possible molecular mechanism that triggers the anti-inflammatory action of ESW, focusing on the possibility that ESW may modulate endogenous nitric oxide (NO) production either under normal or inflammatory conditions. Data on the rapid enhancement of endothelial NO synthase (eNOS) activity in ESW-treated cells suggest that increased NO levels and the subsequent suppression of NF- B activation may account, at least in part, for the clinically beneficial action on tissue inflammation. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,622 |
OBJECTIVES ::: To estimate the short-term benefit and risk of side-effects of injectable gold for rheumatoid arthritis. ::: ::: ::: SEARCH STRATEGY ::: We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. ::: ::: ::: SELECTION CRITERIA ::: Randomized clinical trials (RCT) comparing injectable gold against placebo in patients with rheumatoid arthritis were included. ::: ::: ::: DATA COLLECTION AND ANALYSIS ::: Methodological quality of the RCTs was asessed by two reviewers (MS, BS) (kappa=1.0). Rheumatoid arthritis outcome measures were extracted by two reviewers from the publications for the 6 month endpoint. Sufficient data was obtained to conduct a pooled analysis of the number of swollen joints, physician global assessment, patient global assessment and erythrocyte sedimentation rate (ESR). Results were analyzed as standardized weighted mean differences for swollen joints and global assessments and weighted mean differences for ESR. Toxicity was evaluated with pooled odds ratios for withdrawals. Heterogeneity was estimated using a chi-square test. Fixed effects models were used throughout. ::: ::: ::: MAIN RESULTS ::: Four trials and 415 patients were included. A statistically significant benefit was observed for injectable gold when compared to placebo. The standardized weighted difference (effect size) between gold and placebo for the number of swollen joints was -0.5, translating into a percentage change of 30% in favour of gold adjusted for placebo. Statistically significant differences were also observed for ESR and patient and physician assessments. Twenty two percent of the treated patients withdrew from toxicity compared to 4% of controls (OR=3.9 - 95%Cl: 2.1 - 7.2). ::: ::: ::: REVIEWER'S CONCLUSIONS ::: Although its use can be limited by the incidence of serious toxicity, injectable gold has an important clinically and statistically significant benefit in the short term treatment of patients with rheumatoid arthritis. | In this study the value of undertaking routine blood and urine estimations was assessed in relation to achieving maximum efficacy and safety in chrysotherapy. It was found that a favourable response to gold was forthcoming in approximately two-thirds of patients and occurred irrespective of the patients' disease duration or severity, or the mean serum gold level or the mean urinary gold excretion, estimated immediately before the next gold injection was due. The presence of rheumatoid nodules and the patients' advancing age were associated with a less favourable clinical response to gold. Those patients who derived a marked benefit from chrysotherapy did so significantly earlier in their course than those who derived only moderate benefit. A frequent correlation was seen in individual patients between serum gold levels and urinary gold excretion. This was most marked in those patients showing a favourable response to gold. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,623 |
Selenoprotein T (SELENOT, SELT) is a thioredoxin-like enzyme anchored at the endoplasmic reticulum (ER) membrane, whose primary structure is highly conserved during evolution. SELENOT is abundant in embryonic tissues and its activity is essential during development since its gene knockout in mice is lethal early during embryogenesis. Although its expression is repressed in most adult tissues, SELENOT remains particularly abundant in endocrine organs such as the pituitary, pancreas, thyroid and testis, suggesting an important role of this selenoprotein in hormone production. Our recent studies showed indeed that SELENOT plays a key function in insulin and corticotropin biosynthesis and release by regulating ER proteostasis. Although SELENOT expression is low or undetectable in most cerebral structures, its gene conditional knockout in brain provokes anatomical alterations that impact mice behavior. This suggests that SELENOT also plays an important role in brain development and function. In addition, SELENOT is induced after injury in brain or liver and exerts a cytoprotective effect. Thus, the data gathered during the last ten years of intense investigation of this newly discovered thioredoxin-like enzyme point to an essential function during development and in adult endocrine organs or lesioned brain, most likely by regulating ER redox circuits that control homeostasis and survival of cells with intense metabolic activity. | AIM ::: Selenoprotein T (SelT or SELENOT) is a novel thioredoxin-like enzyme whose genetic ablation in mice results in early embryonic lethality. SelT exerts an essential cytoprotective action during development and after injury through its redox-active catalytic site. This study aimed to determine the expression and regulation of SelT in the mammalian heart in normal and pathological conditions and to evaluate the cardioprotective effect of a SelT-derived peptide, SelT43-52(PSELT) encompassing the redox motif which is key to its function, against ischaemia/reperfusion(I/R) injury. ::: ::: ::: METHODS ::: We used the isolated Langendorff rat heart model and different analyses by immunohistochemistry, Western blot and ELISA. ::: ::: ::: RESULTS ::: We found that SelT expression is very abundant in embryo but is undetectable in adult heart. However, SelT expression was tremendously increased after I/R. PSELT (5 nmol/L) was able to induce pharmacological post-conditioning cardioprotection as evidenced by a significant recovery of contractility (dLVP) and reduction of infarct size (IS), without changes in cardiac contracture (LVEDP). In contrast, a control peptide lacking the redox site did not confer cardioprotection. Immunoblot analysis showed that PSELT-dependent cardioprotection is accompanied by a significant increase in phosphorylated Akt, Erk-1/2 and Gsk3α-β, and a decrement of p38MAPK. PSELT inhibited the pro-apoptotic factors Bax, caspase 3 and cytochrome c and stimulated the anti-apoptotic factor Bcl-2. Furthermore, PSELT significantly reduced several markers of I/R-induced oxidative and nitrosative stress. ::: ::: ::: CONCLUSION ::: These results unravel the role of SelT as a cardiac modulator and identify PSELT as an effective pharmacological post-conditioning agent able to protect the heart after ischaemic injury. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,624 |
BACKGROUND ::: Clinicoradiological variability of vertebrobasilar dolichoectasia (VBD) is known. Little is known about cardiovascular disease (CVD) risk and neuroradiological profiles of asymptomatic VBD. ::: ::: ::: METHODS ::: A total of 7,345 adults (5,534 men and 1,811 women) underwent physical checkup (PC) and brain magnetic resonance (MR) studies between 2004 and 2007. Asymptomatic VBD was diagnosed by neurological examination and MR angiography. Neuroradiological features were analyzed in VBD subjects. CVD risk factors were compared between VBD subjects and 5,000 controls matched by sex and age. ::: ::: ::: RESULTS ::: Ninety-six subjects (85 men and 11 women) had asymptomatic VBD. The detection rate was 1.3% and the male/female ratio 2.5. The mean age +/- SD was 60.4 +/- 10.6 years (60.0 +/- 10.2 in men and 64.0 +/- 13.1 in women). As compared to controls, the frequency of hypertension, obesity, smoking, dyslipidemia, diabetes mellitus and a family history of stroke or CVD was increased significantly in VBD subjects. The mean diameter +/- SD of the basilar artery (BA) was 4.7 +/- 0.2 mm. Only 4 subjects (4%) had a severe degree of elongation and lateral displacement of the BA. Contact of the vertebral artery with the rostral ventrolateral medulla (AMC) was found in 81 subjects: right AMC in 22 subjects and left AMC in 59 subjects. Frequency of hypertension was significantly higher in the left-AMC subjects (57%) than in subjects with right AMC (9%) and no AMC (5%). Other neuroradiological findings revealed small infarcts in 42 subjects, brainstem compression in 4, hydrocephalus in 4 and brain saccular aneurysm in 3. ::: ::: ::: CONCLUSIONS ::: Asymptomatic VBD was detected in 1.3% of the Japanese PC group. Our data indicated male predominance, multiple CVD risk factors, neurovascular hypertension and small infarcts in asymptomatic VBD. | Object. Vertebrobasilar nonsaccular intracranial aneurysms (NIAs) are characterized by elongation, dilation, and tortuosity of the vertebrobasilar arteries. The goal of this study was to define the frequency, predictors, and clinical outcome of the enlargement of vertebrobasilar NIAs. Methods. Patients with vertebrobasilar fusiform or dolichoectatic aneurysms demonstrated on imaging studies between 1989 and 2001 were identified. In particular, patients who had undergone serial imaging were included in this study and their medical records were retrospectively reviewed. Prospective information was collected from medical records or death certificates when available. Both initial and serial imaging studies were reviewed. The authors defined NIA enlargement as a change in lesion diameter greater than 2 mm or noted on the neuroradiologist's report. A Cox proportional hazards regression was used to model time from diagnosis of the vertebrobasilar NIA to the first documented enlargement as a function of various p... | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,625 |
PURPOSE OF REVIEW ::: The outcome of vascularized composite allografts (VCA) often appear unrelated to the presence of donor-specific antibodies (DSA) in blood of the recipient or deposition of complement in the graft. The attenuation of injury and the absence of rejection in other types of grafts despite manifest donor-specific immunity have been explained by accommodation (acquired resistance to immune-mediated injury), adaptation (loss of graft antigen) and/or enhancement (antibody-mediated antigen blockade). Whether and how accommodation, adaptation and/or enhancement impact on the outcome of VCA is unknown. Here we consider how recent observations concerning accommodation in organ transplants might advance understanding and resolve uncertainties about the clinical course of VCA. ::: ::: ::: RECENT FINDINGS ::: Investigation of the mechanisms through which kidney allografts avert antibody-mediated injury and rejection provide insights potentially applicable to VCA. Interaction of DSA can facilitate replacement of donor by recipient endothelial cells, modulate or decrease synthesis of antigen, mobilize antigen that in turn blocks further immune recognition and limit the amount of bound antibody, allowing accommodation to ensue. These processes also can explain the apparent dissociation between the presence and levels of DSA in blood, deposition of C4d in grafts and antibody-mediated rejection. Over time the processes might also explain the inception of chronic graft changes. ::: ::: ::: SUMMARY ::: The disrupted tissue in VCA and potential for repopulation by endothelial cells of the recipient establish conditions that potentially decrease susceptibility to acute antibody-mediated rejection. These conditions include clonal suppression of donor-specific B cells, and adaptation, enhancement and accommodation. This setting also potentially highlights heretofore unrecognized interactions between these 'protective' processes. | PURPOSE OF REVIEW ::: We review recent insights into the mechanisms and prevalence of accommodation. Accommodation refers to an acquired resistance of an organ graft to humoral injury and rejection. ::: ::: ::: RECENT FINDINGS ::: Accommodation has been postulated to reflect changes in antibodies, control of complement and/or acquired resistance to injury by antibodies, complement or other factors. We discuss the importance of these mechanisms, highlighting new conclusions. ::: ::: ::: SUMMARY ::: Accommodation may be a common, perhaps the most common, outcome of organ transplantation and, in some systems, a predictable outcome of organ xenotransplantation. Further understanding of how accommodation is induced and by what mechanisms it is manifest and maintained could have a profound impact on transplantation in general and perhaps on other fields. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,626 |
The endogenous cathelicidin peptide LL-37 is strongly expressed at the wound edge early in the process of acute wound healing, but only weakly expressed in chronic wounds. Excessive proteolysis may limit the therapeutic usefulness of exogenous LL-37, especially in ulcers colonized with Pseudomonas aeruginosa that produce elastase, which degrades LL-37. This study investigated the stability of synthetic LL-37 against two types of proteinases in the presence or absence of wound fluid samples (diluted to 10-20%) from nine non-healing venous leg ulcers. Incubation of LL-37 (10 µg/ml) at 37°C for 6 h resulted in complete degradation by the serine proteinase trypsin (≥ 10 ng/ml), while no degradation was observed with matrix metalloproteinase-9. LL-37 susceptibility to trypsin was diminished considerably in the presence of wound fluid, and there was no apparent cleavage of exogenous LL-37 incubated in wound fluid for up to 24 h at 37°C even when using fluids from ulcers with resident P. aeruginosa (n = 2). In conclusion, LL-37 was degraded by trypsin, but not by matrix metalloproteinase-9, and was fairly resistant to proteolytic cleavage ex vivo by incubation with wound fluid from non-healing venous leg ulcers. Thus, the proteolytic environment of chronic wounds does not seem to prevent the therapeutic use of topical LL-37. | It has been hypothesized that excessive activity of matrix metalloproteinases (MMPs), in particular the gelatinases MMP-9 and MMP-2, contributes to poor healing of chronic skin ulcers. We compared MMP-9 and MMP-2 in wound margin biopsies of standardized acute partial-thickness wounds in healthy volunteers (n = 6) and in venous leg ulcer patients (n = 12) with those of chronic wounds of different etiologies (n = 34) by a combination of specific analyses of activity and protein localization. We also studied MMP-14 by immunohistochemistry and in situ hybridization in parallel. Neither MMP-9 (P =.814) nor MMP-2 (P =.742) endogenous activities differed significantly between acute and chronic wound tissues. Acute wound healing was characterized by induction of MMP-9 in the advancing epithelium. In chronic wounds, prominent MMP-9 immunostaining was seen in neutrophils and macrophages in the ulcer bed, but virtually no MMP-9 was detected in wound edge keratinocytes. MMP-2 was increased and activated with acute wound age. MMP-2 was found abundantly in dermal fibroblasts and endothelial cells beneath, but not in new epithelium of acute and chronic wounds. MMP-14 mRNA or protein was detected solely in the stroma of both acute and chronic wounds. In conclusion, the overall activity of gelatinases MMP-9 and MMP-2 was not increased in chronic wounds compared to normally healing wound tissues. Chronic nonhealing wounds may not be caused by excessive gelatinase activity, but are distinguished from healing wounds by an unfavorable distribution and persistance of MMP-9. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,627 |
To demonstrate potential therapeutic effects of kallikrein gene delivery in salt-induced hypertension and renal diseases, we delivered adenovirus carrying the human tissue kallikrein gene (Ad.CMV-cHK) into deoxycorticosterone acetate (DOCA)-salt hypertensive rats. A single intravenous injection of Ad.CMV-cHK caused a delay in the rise of blood pressure that began 2 days post gene delivery and lasted for more than 23 days. A maximal blood pressure reduction of 50 mm Hg was observed in rats receiving kallikrein gene delivery, as compared to rats receiving adenovirus containing the luciferase gene (Ad.CMV-Luc) (172 ± 5 vs. 222 ± 13 mm Hg, n = 6, P < 0.01). Throughout the experimental period, a blood pressure reduction of at least 32 mm Hg was observed in the DOCA-salt rats injected with Ad.CMV-cHK as compared to DOCA-salt rats receiving control adenovirus. Immunoreactive human tissue kallikrein levels were detected in rat serum and urine post gene delivery. Adenovirus-mediated kallikrein gene delivery caused a significant reduction in urinary excretion, urinary protein levels and body weight. Morphological examination of the kidney showed that kallikrein gene transfer significantly reduced DOCA-salt-induced glomerular sclerotic lesions, brush border disruption of proximal tubules, tubular dilatation and protein cast accumulation. These findings showed that the expression of human tissue kallikrein via gene delivery has protective effects against hypertension and renal injury in DOCA-salt hypertensive rats. | Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector containing human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and concentration of the viral particles to achieve 5x10(9) to 1x10(10) colony-forming units per milliliter. The ability of concentrated infectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral particles (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulted in functional expression of the HHO-1 gene and attenuation of the development of hypertension. Rats expressing HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous significant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and promotes body growth in spontaneously hypertensive rats. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,628 |
ABSTRACTObjectives: As plasma and salivary total antioxidant capacity (TAC) is mainly contributed by uric acid (UA), the present study measures non-urate TAC (Nu-TAC). The aim of the study was to correlate plasma native TAC, Nu-TAC and UA with their salivary analogues, and compare the UA contribution in both body fluids using two different methods.Methods: The study involved 55 middle-aged and older subjects (66.7 ± 4.5 years). TAC was determined simultaneously with two methods (ferric reducing ability of plasma – FRAP, 2.2-diphenyl-1-picryl-hydrazyl – DPPH and countertypes for saliva – FRAS and DPPHS test), with and without UA (native TAC and Nu-TAC, respectively). Plasma UA and salivary UA (SUA) were assessed.Results: Subjects with increased FRAP, DPPH and UA had higher FRAS, DPPHS and SUA, respectively (P < 0.05). Plasma Nu-TAC indices did not correlate with salivary Nu-TAC. The contribution of UA to the plasma and salivary DPPH tests was similar: 75.7 ± 10.3% and 75.2 ± 14.0%, respectively. However, t... | The native Total Antioxidant Capacity (TAC) of plasma and saliva is generally determined by uric acid (UA). Several studies have assessed the impact of habitual dietary antioxidative vitamin intake on TAC, but it remains unknown whether it influences Non-Urate Total Antioxidant Capacity (Nu-TAC), i.e., TAC after enzymatic UA elimination. The purpose of this study was to assess whether the intake of antioxidative vitamins C, E, and β-carotene, provided with usual daily food rations, affects plasma and salivary Nu-TAC. The study involved 56 older subjects (aged 66.9 ± 4.3 years), divided into two age- and sex-matched groups: group 1 (n = 28), with lower combined vitamin C, E, and β-carotene intake, and group 2 (n = 28), with higher intake. A 24 h dietary recall was obtained from each individual. Nu-TAC was assessed simultaneously with two methods in plasma (Ferric Reducing Ability of Plasma—Nu-FRAP, 2.2-diphenyl-1-picryl-hydrazyl—Nu-DPPH) and in saliva (Nu-FRAS and Nu-DPPHS test). No differences were found in the Nu-TAC parameters between the groups, either in plasma (Nu-FRAP, Nu-DPPH) or in saliva (Nu-FRAS, Nu-DPPHS) (p > 0.05). No plasma or salivary Nu-TAC indices correlated with dietary vitamin C, E, or β-carotene intake or with other nutrients. Habitual, not extra-supplemented dietary intake does not significantly affect plasma or salivary Nu-TAC. | Let G denote a compact connected Lie group, with maximal torus T (of dimension d, say). Let n: G--t M,,C be a unitary representation, and form the nJL UHF C* algebra A = 0 M,,C (n is fixed); this is the infinite tensor product of copies of the n On matrix ring. We have an action tt: G 3 Aut(A), by setting a(g) = 0 Ad n(g), B. M. Baker suggested the name Xerox product type action, because the representation 7c is duplicated over and over. We may form the crossed product A x 1 G and the fixed point algebra A”” (or simply AC if there is little likelihood of ambiguity). By restriction of c( to T, we also obtain a Xerox action of the d-torus T (also called CI). Clearly AC is a unital subalgebra of A ‘. The principal result asserts that every trace on AC extends to a trace on A ‘. In the course of the proof, we also show that the Grothendieck group of A”, K,(AG), is finitely generated as a ring, and that KO(AT) (which is also a ring) is finitely generated as a K,,( A’)-module. There are several consequences of these results. The space of faithful pure traces on AG is a dense open subset of the pure trace space of A’, and moreover is homeomorphic to (Rd)+ +/W, the orbit space of the strictly positive d-tuples under the natural action of the Weyl group, provided that o! is faithful. If B= @FL, M,,,,C is a UHF algebra with corresponding product type action (not necessarily Xerox) /? = 0 Ad nrr then the natural inclusion A ‘3’ -+ (A @ B)G301 @ B induces a bijection on faithful pure traces (if c( is faithful), and the set of the latter is dense in the pure trace space of (A @B)‘,“@? Another result (not proved here) using the main result of the article asserts that a difference of characters of G divides an actual character (within the representation ring of G) if and only if its restriction to T divides a character of T. | eng_Latn | 22,629 |
Skin wound healing is complex and involves the processes of many factors, among which angiogenesis and inflammatory responses play important roles. New blood vessels provide nutrition and oxygen for skin wound repair. Cytokines in skin wounds, which include pro-inflammatory and anti-inflammatory factors, can modulate the inflammatory response. Therefore, treatment strategies that promote angiogenesis and modulate the inflammatory response in skin wounds can accelerate skin wound healing. This study explored the effects of peptide Ser-Ile-Lys-Val-Ala-Val (SIKVAV)-modified chitosan hydrogels in skin wound healing. General observation demonstrated that SIKVAV-modified chitosan hydrogels promoted the contraction of skin wounds compared with the negative and positive controls. Masson's trichrome staining indicated that peptide-modified chitosan hydrogels accelerated the deposition of more collagen fibers in the skin wounds compared with the negative and positive controls. Immunohistochemistry assays showed that more myofibroblasts were deposited and more angiogenesis was found in skin wounds treated with peptide-modified chitosan hydrogels compared with the negative and positive controls. In addition, qRT-PCR assays showed that peptide-modified chitosan hydrogels promoted the expression of TGF-β1 (transforming growth factor-β1) mRNA and inhibited the expression of TNF-α (tumor necrosis factor-α) mRNA and IL-1β (Interleukin-1β) mRNA and IL-6 (Interleukin-6) mRNA in skin wounds. Taken together, these results indicate the potential of SIKVAV-modified chitosan hydrogels in skin wound healing as complex biomaterials. | Myocardial remodeling following myocardial infarction (MI) is emerging as key causes of chronic infarct mortality. Interleukin-6 is a classic pro-inflammatory cytokine needed to mount an effective immune response. It seems that interleukin-6 acts as an important role in the dynamic and superbly orchestrated process of innate immunity after MI. Interleukin-6 timely suppresses of innate immune signals to prevent the catastrophic consequences of uncontrolled inflammation on cardiac geometry and function, and thus tunes myocardial remodeling. A comprehensive understanding of biological processes of interleukin-6 in innate immunity leading to inflammatory response and disease-related ventricular remodeling is helpful to find the solution of chronic heart failure. To accomplish this, we reviewed the articles of interleukin-6 regard to inflammation, innate immunity, and cardiac remodeling. This review focuses on the role of interleukin-6 that dominates cell-mediated immunity, especially on neutrophils, monocytes, macrophages, and fibroblasts. In addition, we will also briefly discuss other inflammatory cytokines involved in this process within the paper. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,630 |
A new portable plethysmograph is described which is all metal and, therefore, sturdy and free from the difficulties of deterioration—an important problem when rubber membranes are employed. A device for standardization is incorporated which makes it possible to correct for finger and toe size, thereby resulting in a completed plethysmogram which can be read directly from subject to subject and from time to time in the same subject. This eliminates calculations usually required to convert volume changes to standard units. The plethysmograph also contains a master elapse time recorder which makes it possible to record time even when the camera is off. By means of a baseline adjuster and recorder, gross or large and slow variations in volume of the part can be recorded. The completed plethysmogram is discussed and five types of spontaneous deflections in volume are considered. The plethysmogram shows the volume changes at slow and fast speeds. The former makes it possible to study all five types of spontaneous deflections in volume, while the latter makes it possible to study the configurations of the pulse wave in detail. A discussion of the methods of recording the plethysmogram, precautions and possible errors in recording, and its interpretation are given. The use of plethysmography in the study of peripheral vascular disease, psychogenic states, and states of relaxation and tension are briefly indicated. Detailed applications of the plethysmogram to normal and abnormal clinical states will be presented in the near future. This plethysmograph is a new instrument which is objective, precise, simple, and practical. It has great promise in the study of many problems in health and disease which manifest themselves by disturbances in the blood vessels, lymphatics, and intercellular and intracellular and fluid volumes of the tips of the fingers and toes. By far the greatest number of experimental and clinical applications remain unknown. As with the introduction of any new instrument which has applications in the biologic fields generally and broad use in these fields, the science is in its infancy. It is only with the patient efforts of many investigators, both in the laboratory and the clinic, that the plethysmograph and plethysmogram will develop and reach a state of adequate evaluation and proper usage. | A short historical note on plethysmography is given and the development of the modern computerized pneumoplethysmograph is described. The computer-aided pneumoplethysmogram (CAP), with proper programming, makes possible numerous computations that give new, useful, and rapid information about the patient. New applications of the CAP will quickly develop and the data collected will be quickly analyzed and displayed. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,631 |
A sensitive, specific and rapid liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for analysis of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rat plasma using sulfamethoxazole as an internal standard (IS). Separation was conducted out on an Agilent Eclipse XDB C18 column with liner gradient elution using acetonitrile (A) and 0.1% aqueous acetic acid (B). A tandem mass spectrometric detection was conducted using multiple reaction monitoring (MRM) via an electrospray ionization (ESI) source. A novel multi-determination-periods program was executed to achieve a higher sensitivity by setting three scanning periods. All analytes exhibited good linearity within the concentration range (r>0.9973). The lower limits of quantitation (LLOQ) of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin were 2.64, 4.32, 2.32 and 1.56ng/mL, respectively. Intra-day and inter-day precisions of the investigated components exhibited an RSD within 8.3%, and the accuracy (RE) ranged from -8.6% to 6.0% at all quality control levels. The developed method was successfully applied to a pharmacokinetic study of ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin in rats after oral administration of a Weifuchun tablet. | Context: Oridonin has been traditionally used in Chinese treatment of various cancers, but its poor bioavailability limits its therapeutic uses. Verapamil can enhance the absorption of some drugs with poor oral bioavailability. Whether verapamil can enhance the bioavailability of oridonin is still unclear.Objective: This study investigated the effect of verapamil on the pharmacokinetics of oridonin in rats and clarified its main mechanism.Materials and methods: The pharmacokinetic profiles of oral administration of oridonin (20 mg/kg) in Sprague-Dawley rats with two groups of six animals each, with or without pre-treatment of verapamil (10 mg/kg/day for 7 days) were investigated. The effects of verapamil on the transport and metabolic stability of oridonin were also investigated using Caco-2 cell transwell model and rat liver microsomes.Results: The results showed that verapamil could significantly increase the peak plasma concentration (from 146.9 ± 10.17 to 193.97 ± 10.53 ng/mL), and decrease the oral clearance (from 14.69 ± 4.42 to 8.09 ± 3.03 L/h/kg) of oridonin. The Caco-2 cell transwell experiments indicated that verapamil could decrease the efflux ratio of oridonin from 1.67 to 1.15, and the intrinsic clearance rate of oridonin was decreased by the pre-treatment with verapamil (40.06 ± 2.5 vs. 36.09 ± 3.7 µL/min/mg protein).Discussion and conclusions: These results indicated that verapamil could significantly change the pharmacokinetic profile of oridonin in rats, and it might exert these effects through increasing the absorption of oridonin by inhibiting the activity of P-gp, or through inhibiting the metabolism of oridonin in rat liver. In addition, the potential drug-drug interaction should be given special attention when verapamil is used with oridonin. Also, the dose of oridonin should be carefully selected in the clinic. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,632 |
INTRODUCTION 345 STRUCTURE AND FUNCTION OF FERRITIN AND TRANSFERRIN RECEPTOR 348 THE IRON-RESPONSE ELEMENT ........ ..... . . . . . . . . ... . . . ... . . . . . . . . . . . . . . . . . . . . . . .. .. .. . . . . 349 STRUCTURE AND FUNCTION OF THE IRON-RESPONSIVE ELEMENT BINDING PROTEINS (IRE-BPs) 35 1 Conservation of IRE-BPs.. . .. . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .. . . . . ... . . . . . . . . . . . .. . . . . .. . . 35 1 Purification, Cloning, and Characterization of IRE-BPs .. ..... ........ ...... . . . . . . . . . . . . 351 IRON-DEPENDENT POSTTRANSCRIPTIONAL REGULATION BY IRE-BPs . . ..... , 353 Translational Regulation by IRE-BPs . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . .. . . . . . . .. . . . 353 Stabilization of TjR mRNA by IRE-BPs.... .. .... . . . .. . . . .. . . . . . .. . . . . . . . . . . . ... . . .. . . . . . . . .. 357 A Model for the Coordinate Regulation of Ferritin and TjR by IRE-BPs .. 358 MECHANISM OF ACTIVATION OF IRE-BPs BY IRON 360 RELATED FAMILIES OF IRE-BPs 363 CONCLUDING REMARKS 363 | OBJECTIVE ::: An increased oxidative stress in the lower respiratory tract of individuals with acute respiratory distress syndrome is considered to be one mechanism of lung injury in these patients. Cell and tissue damage resulting from an oxidative stress can ultimately be the consequence of a disruption of normal iron metabolism and an increased availability of catalytically active metal. Using bronchoalveolar lavage fluid, we quantified concentrations of iron and iron-related proteins in the lower respiratory tract in patients with acute respiratory distress syndrome and healthy volunteers. ::: ::: ::: DESIGN ::: A clinical study to quantify iron and iron-related proteins in the lower respiratory tract in patients with acute respiratory distress syndrome and healthy volunteers. ::: ::: ::: PATIENTS ::: We studied 14 patients with acute respiratory distress syndrome and 28 healthy volunteers. ::: ::: ::: MAIN RESULTS ::: Comparable to previous investigation, protein, albumin, and cytokine concentrations in the bronchoalveolar lavage fluid were significantly increased in acute respiratory distress syndrome patients. The concentrations of total and nonheme iron were also increased in the lavage fluid of patients. Concentrations of hemoglobin, haptoglobin, transferrin, transferrin receptor, lactoferrin, and ferritin in the bronchoalveolar lavage fluid were all significantly increased in acute respiratory distress syndrome patients. ::: ::: ::: CONCLUSIONS ::: We conclude that bronchoalveolar lavage fluid indices reflect a disruption of normal iron metabolism in the lungs of acute respiratory distress syndrome patients. Increased concentrations of available iron in acute respiratory distress syndrome may participate in catalyzing oxidant generation destructive to the tissues of the lower respiratory tract. However, increased metal availability is also likely to elicit an increased expression of transferrin receptor, lactoferrin, and ferritin in the lower respiratory tract which will function to diminish this oxidative stress. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | yue_Hant | 22,633 |
AIMS ::: To investigate the accuracy of the sequential combination of the probe-to-bone test and plain X-rays for diagnosing osteomyelitis in the foot of patients with diabetes. ::: ::: ::: METHODS ::: We prospectively compiled data on a series of 338 patients with diabetes with 356 episodes of foot infection who were hospitalized in the Diabetic Foot Unit of La Paloma Hospital from 1 October 2002 to 31 April 2010. For each patient we did a probe-to-bone test at the time of the initial evaluation and then obtained plain X-rays of the involved foot. All patients with positive results on either the probe-to-bone test or plain X-ray underwent an appropriate surgical procedure, which included obtaining a bone specimen that was processed for histology and culture. We calculated the sensitivity, specificity, predictive values and likelihood ratios of the procedures, using the histopathological diagnosis of osteomyelitis as the criterion standard. ::: ::: ::: RESULTS ::: Overall, 72.4% of patients had histologically proven osteomyelitis, 85.2% of whom had positive bone culture. The performance characteristics of both the probe-to-bone test and plain X-rays were excellent. The sequential diagnostic approach had a sensitivity of 0.97, specificity of 0.92, positive predictive value of 0.97, negative predictive value of 0.93, positive likelihood ratio of 12.8 and negative likelihood ratio of 0.02. Only 6.6% of patients with negative results on both diagnostic studies had osteomyelitis. ::: ::: ::: CONCLUSIONS ::: Clinicians seeing patients in a setting similar to ours (specialized diabetic foot unit with a high prevalence of osteomyelitis) can confidently diagnose diabetic foot osteomyelitis when either the probe-to-bone test or a plain X-ray, or especially both, are positive. | The objective was to determine multidrug-resistant organisms’ (MDROs) profile in diabetic foot ulcers (DFU), antibiotic resistance of MDROs, and to find the potential risk factors for infection with MDROs. In 157 patients with DFU admitted to Tianjin Metabolic Disease Hospital, China, from January 2011 to January 2012, microbiological specimens were taken on admission. The patients were divided into 2 groups according to the infection of MDROs. Potential risk factors for MDRO-positive specimens were examined using univariate and multivariate analyses. Seventy-eight MDRO strains were isolated from patients in the MDRO+ group, among which the top 3 were Staphylococcus aureus (16.7%), Enterobacter spp (16.7%), and Pseudomonas aeruginosa (15.4%). Most of the MDROs were resistant to at least 8 kinds of commonly used antibiotics. Gram-negative MDROs showed 23% to 50% resistance to third-generation cephalosporins. The resistant rates of Gram-positive MDROs to fluoroquinolone were more than 70%; penicillin and se... | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,634 |
OBJECTIVE ::: To study the effect of active fractions from Lycopus lucidus (L. F04) on platelet aggregation and thrombus formation so as to investigate its mechanism of promoting blood circulation and removing blood stasis. ::: ::: ::: METHOD ::: The effects of Lycopus lucidus L. F04 on platelet aggregation induced by ADP in vivo, and thrombosis of artery-vein by-pass and thrombus formed in circuitous loop in vitro were examined using the blood stasis animal model of rats made by injecting high molecular weight dextran (HMWD). ::: ::: ::: RESULT ::: The increase of maximum platelet aggregation rate induced by ADP in vivo in HMWD model was evidently inhibited with 0.408 g/kg or 0.204 g/kg or L. F04, and the effect showed a trend of concentration-dependence. As compared with the control, the thrombus weight in rat model of blood stasis increased clearly and its length showed only a trend of increase. Both 0.408 g/kg and 0.204 g/kg of L. F04 had the effect of resisting the thrombus formation, while 0.408 g/kg showed better effects of reducing the thrombus dry weight and wet weight. Both 0.408 g/kg and 0.204 g/kg of L. F04 could inhibit the thrombosis in artery-vein by-pass; the inhibition rates were 27.41% and 27.14% respectively. ::: ::: ::: CONCLUSION ::: Lycopus lucidus L. F04 could significantly inhibit platelet aggregation and thrombus formation. | Lycopus lucidus Turcz. ex Benth (LT) has been broadly used as a traditional medicinal herb in Asia including Korea, China, and Japan due to its noted ability to promote blood circulation and remove blood stasis. However, its anticancer mechanism is not understood. This study aims to elucidate the effects of ethanol extracts of LT (ELT) relative to the role of Runt-related transcription factor- (Runx-) 2 in the invasive and metastatic potentials of mouse colon cancer to determine the underlying mechanisms involved. ELT was evaluated for the antimetastasis activity using CT-26 colon cancer using wound healing, transwell matrigel, and western blot analysis. We used Runx-2-specific siRNA to further determine the relationship between Runx-2 and matrix metalloprotease- (MMP-) 9 in the migration and invasion of CT-26 cells. Runx-2 was first demonstrated to be a transcription factor that plays a remarkable role in diverse biological processes of chondrocytes and osteoblasts, but recently, Runx-2 has been reported to be associated with the progression of certain human cancers. ELT was not altered in its effects on growth inhibition. However, ELT significantly inhibited wound closure and cell invasion in a dose-dependent manner. ELT decreased the metastasis by regulating the activity of MMP-9 and Runx-2 at the translational levels. Our results demonstrate that ELT decreases metastasis by inhibiting the Runx-2-MMP-9 axis. We suggest that it can be used as a novel agent in therapeutic strategies for combating colon cancer. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,635 |
BACKGROUND ::: We investigated potential for hypersensitivity reactions after repeated sugammadex administration and explored the mechanism of hypersensitivity. ::: ::: ::: METHODS ::: In this double-blind, placebo-controlled study (NCT00988065), 448 healthy volunteers were randomised to one of three arms to receive three repeat i.v. administrations of either sugammadex 4 mg kg-1, 16 mg kg-1, or placebo. Primary endpoint was percentage of subjects with hypersensitivity (assessed by an independent adjudication committee). Secondary endpoint of anaphylaxis was classified per Sampson and Brighton criteria. Exploratory endpoints included skin testing, serum tryptase, anti-sugammadex antibodies [immunoglobulin (Ig) E/IgG], and other immunologic parameters. ::: ::: ::: RESULTS ::: Hypersensitivity was adjudicated for 1/148 (0.7%), 7/150 (4.7%), and 0/150 (0.0%) subjects after sugammadex 4 mg kg-1, 16 mg kg-1, and placebo, respectively. After sugammadex 16 mg kg-1, one subject met Sampson criterion 1 and Brighton level 1 (highest certainty) anaphylaxis criteria; two met Brighton level 2 criteria. After database lock it was determined that certain protocol deviations could have introduced bias in the reporting of hypersensitivity signs/symptoms in a subject subset. Objective laboratory investigations indicated that potential underlying hypersensitivity mechanisms were unlikely to have been activated; the results suggest that most of the observed hypersensitivity reactions were unlikely IgE/IgG-mediated. ::: ::: ::: CONCLUSION ::: Dose-dependent hypersensitivity or anaphylaxis reactions to sugammadex were observed when administered without prior neuromuscular blocking agent. Laboratory investigations do not suggest prevalent allergen-specific IgE/IgG-mediated immunologic hypersensitivity. Because it could not be fully excluded that estimates of hypersensitivity/anaphylaxis incidence were unbiased, an additional study was conducted to characterise the potential for hypersensitivity reactions and is described in a companion report. ::: ::: ::: CLINICAL TRIAL REGISTRATION ::: http://www.clinicaltrials.gov NCT00988065; Protocol number P06042. | Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,636 |
Sodium stibogluconate (SSG), an inhibitor of SHP-1 that negatively regulates cytokine signaling and immunity, suppressed growth of murine Renca tumors in combination with interleukin-2 (IL-2) via a T-cell-dependent mechanism. The ability of SSG to interact with IL-2 in activating primary human immune cells was evaluated herein by assessing its induction of interferon (IFN)-gamma(+) TH1 cells in human peripheral blood in vitro. The significance of IFN-gamma(+) cells was also investigated by assessing SSG/IL-2 antitumor activity in wild-type and IFN-gamma(-/-) mice. IFN-gamma(+) cells but not IL-5(+) cells were induced markedly (9.1x) in healthy peripheral blood by SSG/IL-2 in contrast to the modest induction by SSG alone (2.1x) at its clinically achievable dose (20 microg/mL) or by IL-2 (3.1x) at its C(max) of low-dose schedule (30 IU/mL). SSG at a higher dose (100 microg/mL) was less effective alone (1.5x) or in combination with IL-2 (7.8x). Peripheral IFN-gamma(+) cells were induced after 4 or 16 h treatment with SSG/IL-2 within CD4(+) and CD8(+) lymphocytes coincided with heightened CD69 expression (approximately 3-4x). SSG/IL-2 was also more effective than the single agents in inducing IFN-gamma(+) cells in the peripheral blood of melanoma patients, whose basal IFN-gamma(+) cell levels were approximately 5% of healthy controls. Renca tumor growth was inhibited by SSG/IL-2 in wild-type but not IFN-gamma(-/-) mice. These results demonstrate SSG interactions with IL-2 in vitro to activate key antitumor immune cells in peripheral blood of healthy and melanoma donors, providing further evidence for proof of concept clinical trials for effecting augmentation of IL-2 through inhibiting negative regulatory protein tyrosine phosphatases. | BACKGROUND ::: Therapeutic response in infectious disease involves host as well as microbial determinants. Because the immune and inflammatory response to Leishmania (Viannia) species defines the outcome of infection and efficacy of treatment, immunomodulation is considered a promising therapeutic strategy. However, since Leishmania infection and antileishmanial drugs can themselves modulate drug transport, metabolism and/or immune responses, immunotherapeutic approaches require integrated assessment of host and parasite responses. ::: ::: ::: METHODOLOGY ::: To achieve an integrated assessment of current and innovative therapeutic strategies, we determined host and parasite responses to miltefosine and meglumine antimoniate alone and in combination with pentoxifylline or CpG 2006 in peripheral blood mononuclear cells (PBMCs) of cutaneous leishmaniasis patients. Parasite survival and secretion of TNF-α, IFN-γ, IL-10 and IL-13 were evaluated concomitantly in PBMCs infected with Luc-L. (V.) panamensis exposed to meglumine antimoniate (4, 8, 16, 32 and 64 μg SbV/mL) or miltefosine (2, 4, 8, 16 and 32 μM HePC). Concentrations of 4 μM of miltefosine and 8 μg SbV/mL were selected for evaluation in combination with immunomodulators based on the high but partial reduction of parasite burden by these antileishmanial concentrations without affecting cytokine secretion of infected PBMCs. Intracellular parasite survival was determined by luminometry and cytokine secretion measured by ELISA and multiplex assays. ::: ::: ::: PRINCIPAL FINDINGS ::: Anti- and pro-inflammatory cytokines characteristic of L. (V.) panamensis infection were evaluable concomitantly with viability of Leishmania within monocyte-derived macrophages present in PBMC cultures. Both antileishmanial drugs reduced the parasite load of macrophages; miltefosine also suppressed IL-10 and IL-13 secretion in a dose dependent manner. Pentoxifylline did not affect parasite survival or alter antileishmanial effects of miltefosine or meglumine antimoniate. However, pentoxifylline diminished secretion of TNF-α, IFN-γ and IL-13, cytokines associated with the outcome of infection by species of the Viannia subgenus. Exposure to CpG diminished the leishmanicidal effect of meglumine antimoniate, but not miltefosine, and significantly reduced secretion of IL-10, alone and in combination with either antileishmanial drug. IL-13 increased in response to CpG plus miltefosine. ::: ::: ::: CONCLUSIONS AND SIGNIFICANCE ::: Human PBMCs allow integrated ex vivo assessment of antileishmanial treatments, providing information on host and parasite determinants of therapeutic response that may be used to tailor therapeutic strategies to optimize clinical resolution. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,637 |
The clinical signs and pathology in an outbreak of toxicity in feedlot cattle attributed to the ingestion of toxic levels of the ionophore antibiotic salinomycin over an extended period of 11 weeks are described. Thirty-nine out of 380 cattle developed signs consistent with cardiac failure and 8 of these died. Clinical signs included dyspnoea, tachypnoea, tachycardia and exercise intolerance. Two cattle were necropsied and in one there were macroscopic lesions suggestive of congestive heart failure, namely pulmonary oedema, hydrothorax and hepatomegaly. Histopathology revealed a chronic cardiomyopathy characterised principally by extensive myocardial fibre atrophy with multifocal hypertrophy and interstitial and replacement fibrosis. Hepatic and pulmonary lesions were consistent with those of congestive cardiac failure. The myocardial lesions in this outbreak were similar to those encountered in cases of a chronic toxicity associated with the ingestion of litter derived from poultry rations containing ionophores (ionophore-associated poultry litter toxicity). Hence, the clinical and pathological findings in this outbreak indicate that in cattle, the prolonged ingestion of ionophores over several weeks may result in the development of chronic myocardial lesions comparable to those of IAPLT but significantly different from those encountered in the more traditional acute outbreaks of ionophore toxicity as described in the literature. | Salinomycin is a monocarboxylic polyether antibiotic with antimicrobial and anticoccidial properties. Although it has proved to be safe at therapeutic doses, toxic effects can result from overdosage or misuse. In addition to clinical signs and pathologic lesions, confirmatory diagnosis of toxicosis needs consideration of laboratory assays. The present study describes changes in biochemical parameters over an extended period of 35 days in calves administered toxic levels of sodium salinomycin. Eleven calves (90 to 130 kg, from both sexes) were randomly divided into three experimental groups (group 1, four male calves; group 2, three male calves; and group 3, four female calves). Blood samples were collected from jugular vein before administration of salinomycin as the control. Group 1 was given salinomycin at a dosage rate of 5 mg/kg twice a day for two consecutive days; groups 2 and 3 were similarly administered with the same drug but at 4 mg/kg. Following drug administration, blood samples were collected at different times (1, 2, 4, 7, 10, 11, 14, 21, 28, and 35 days), and their biochemical parameters (ALT, AST, CK, creatinine, calcium, phosphorus, sodium, potassium, chloride, and total protein) were determined using conventional laboratory methods. Results indicated a significant increase in the activities of ALT, AST, and CK. Concentrations of creatinine, potassium, phosphorous, and blood urea nitrogen in the serum were also significantly elevated. In contrast, concentrations of serum chloride, sodium, and calcium were significantly decreased. However, no significant change was observed in the level of serum total protein. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,638 |
Regression of Barrett's epithelium after antireflux operations remains a controversial topic. We evaluated the effect of antireflux procedures in patients with Barrett's esophagus on the regression of columnar epithelium and dysplasia and its potential protective effect on the subsequent development of carcinoma. Of the 241 patients with Barrett's esophagus treated at the Lahey Clinic from 1973 to 1989, 37 patients underwent an antireflux operation. Regression was defined as histological evidence of regenerating squamous mucosa that completely or partially replaced the columnar epithelium. Improvement in lower esophageal sphincter pressure to 12 mm Hg or greater occurred in 19 of 26 patients (73%) who had perioperative manometry. Symptomatic relief of esophagitis occurred in 34 of 37 patients (92%). Four patients had partial regression with regenerating squamous mucosa juxtaposed with areas of columnar epithelium. Carcinoma developed in 3 of 37 patients (8.1%). One patient had recurrence of severe symptoms of reflux esophagitis before development of carcinoma. Patients with Barrett's esophagus who have undergone a successful antireflux operation with symptomatic relief and evidence of improvement in lower esophageal sphincter pressures rarely show regression of Barrett's mucosa and may still be at risk for development of carcinoma. Therefore, the indications for antireflux operation in Barrett's esophagus should remain the same as for other patients with gastroesophageal reflux, but yearly endoscopic and histological surveillance should be continued postoperatively. | The objective of this study was to determine whether gastric secretion of acid and pepsin is different in the subset of esophagitis patients who also have Barrett's esophagus. Basal and stimulated gastric secretions were studied for 1 hr in the unstimulated state and 1 hr after pentagastrin 6 microg/kg subcutaneous injection. Because Barrett's patients are predominantly male, the 30 patients were matched with patients who had esophagitis, but not Barrett's, for sex (26 men, 4 women) and age as well as for background gastrointestinal disease (duodenal ulcer in 10, no ulcer disease in 17 and Zollinger-Ellison hypersecretors in 3). Patients with Barrett's weighed more than controls (P < 0.05). Acid and pepsin output in the basal and stimulated state were no different in Barrett's and their appropriately matched controls. Overnight fasting residue--volume, pH, acid and pepsin concentrations, and bile content--were also alike. The severity of esophagitis or prevalence of esophageal ulcer or stricture was not different between those with and without Barrett's and in neither was the grade of esophagitis related to acid or pepsin output. It is concluded that Barrett's esophagus patients do not have gastric secretions different from appropriately matched controls with esophagitis alone. When present, esophagitis due to reflux in Barrett's epithelium should be treated on its merits by appropriate reduction of acid exposure. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,639 |
INTRODUCTION ::: The purpose of this study was to analyze the influence of metabolic phenotypes during the construction of ROC curves for waist circumference (WC) cutpoint selection. ::: ::: ::: MATERIALS AND METHODS ::: A total of 1,902 subjects of both genders were selected from the Maracaibo City Metabolic Syndrome Prevalence Study database. Two-Step Cluster Analysis (TSCA) was applied to select metabolically healthy and sick men and women. ROC curves were constructed to determine WC cutoff points by gender. ::: ::: ::: RESULTS ::: Through TSCA, metabolic phenotype predictive variables were selected: HOMA2-IR and HOMA2-βcell for women and HOMA2-IR, HOMA2-βcell, and TAG for men. Subjects were classified as healthy normal weight, metabolically obese normal weight, healthy and metabolically disturbed overweight, and healthy and metabolically disturbed obese. Final WC cutpoints were 91.50 cm for women (93.4% sensitivity, 93.7% specificity) and 98.15 cm for men (96% sensitivity, 99.5% specificity). ::: ::: ::: CONCLUSIONS ::: TSCA in the selection of the groups used in ROC curves construction proved to be an important tool, aiding in the detection of MOWN and MHO which cannot be identified with WC alone. The resulting WC cutpoints were <91.00 cm for women and <98.00 cm for men. Furthermore, anthropometry is insufficient to determine healthiness, and, biochemical analysis is needed to properly filter subjects during classification. | Over the past 2 decades, there has been a dramatic increase in the number of subjects with the metabolic syndrome in Japan as well as in Western countries. Because subjects with the metabolic syndrome have an elevated risk of development of type 2 diabetes and cardiovascular diseases (1–3), there is an urgent need to establish strategies to prevent an epidemic of this syndrome. In particular, a practical and sensitive screening system must be established to detect the metabolic syndrome. At present, there are two internationally recognized definitions of the metabolic syndrome, namely those of the World Health Organization (4) and the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP III) (5). In an attempt to establish a unified definition for the metabolic syndrome, the International Diabetes Federation (IDF) has very recently announced a new definition of the metabolic syndrome that is expected to be suitable for use in clinical practice worldwide (6). The IDF defines metabolic syndrome as the presence of central obesity plus any two of the following four factors (raised triglyceride level, reduced HDL cholesterol, raised blood pressure, and raised fasting plasma glucose). The IDF recommended that the cutoff level used for the waist circumference to define central obesity should be different among different ethnic groups (7). In fact, the new IDF definition has proposed ethnicity-specific cutoff values for waist circumference, namely, 94 and 80 cm for European men and women, respectively, and 85 and 90 … | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,640 |
Background ::: Preoperative portal vein embolization (PVE) induces ipsilateral atrophy of the hepatic parenchyma to be resected, as well as contralateral compensatory hypertrophy of the residual liver. However, there are two potential problems with this technique: inadequate contralateral hypertrophy and tumor progression while waiting for the non-embolized liver to hypertrophy. We devised a strategy to deal with these two problems by performing an ipsilateral hepatic artery embolization 6 weeks after an unsatisfactory PVE in an effort to accelerate the hypertrophy of the remnant liver. | Purpose ::: The impact of chemotherapy (CTx) on morbidity after liver resection for colorectal metastases (CRC-LM) has been increasingly investigated during recent years. Biologic agents like bevacizumab (BEV) or cetuximab (CET) are now added as “targeted therapy” (TT), also in neoadjuvant settings. Initial series could demonstrate the safety of those regimens in liver resection but data are still scarce. We evaluated the impact of CTx with BEV or CET (CTx + TT) on perioperative morbidity and mortality. | It is proved, by using topological properties, that when a group automorphism of a locally compact totally disconnected group is ergodic under the Haar measure, the group is compact. The result is an answer for Halmos's question that has remained open for the totally disconnected case. | eng_Latn | 22,641 |
Oxidative stress is one of the major factors in the pathogenesis of liver disease. Quercetin is a plant-based antioxidant traditionally used as a treatment for hepatic injury, but its poor solubility affects its bioavailability. We here report the regulative effects on hepatoprotection and absorption in mice of quercetin sulfation to form quercetin-5',8-disulfonate (QS), a novel synthetic compound. Oral administration of both QS and the parent quercetin at 100, 200 and 500 mg/kg·bw prior to acute CCl4 oxidative damage in mice, effectively attenuated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities and hepatic malondialdehyde (MDA) levels (p < 0.05), and suppressed the CCl4-induced depletion of glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD). Selective 5',8-sulfation of quercetin increased the hepatoprotective effect, and its relative absorption relative to quercetin (p < 0.05) as indicated by an improved 24-hour urinary excretion and a decreased fecal excretion determined by HPLC. These results and histopathological observations collectively demonstrate that quercetin sulfation increases its hepatoprotective effects and absorption in mice, and QS has potential as a chemopreventive and chemotherapeutic agent for liver diseases. | Renal dysfunction frequently complicates liver disease and, when present, adversely affects prognosis. While a number of conditions can affect both the liver and the kidney acutely (e.g. paracetamol), many hepatotoxic insults (e.g. alcohol or viral hepatitis) cause more problems associated with cirrhosis. This review focuses mainly on the renal dysfunction associated with this chronic liver damage. Chronic liver disease is implicated in changes in vascular reactivity and tone, resulting in a systemic vasodilatation and renal vasoconstriction. In its extreme form it leads to the most feared of all renal complications of liver disease, the hepatorenal syndrome (HRS), which is frequently fatal. The recognition and early management of both the renal dysfunction and liver disease are important to survival. The key therapeutic issues revolve around optimizing the circulating volume, reversing the maladaptive haemodynamic changes, removal of other potential nephrotoxins and early treatment of infection. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,642 |
(2 R ,3 R ,4 R )-4-hydroxy-2-(hydroxymethyl)pyrrolidin-3-yl 4- O -(6-deoxy- β -D-glucopyranosyl)- α -D-glucopyranoside (CS-1036), which is an α -amylase inhibitor, exhibited biphasic and sustained elimination with a long t 1/2 (18.4–30.0 hours) in rats and monkeys, but exhibited a short t 1/2 (3.7–7.9 hours) in humans. To clarify the species differences in the t 1/2, the plasma protein binding of CS-1036 was evaluated by ultrafiltration. A concentration-dependent and saturable plasma protein binding of CS-1036 was observed in rats and monkeys with the dissociation rate constant ( K D) of 8.95 and 27.2 nM, and maximal binding capacity ( B max) of 52.8 and 22.1 nM, respectively. By the assessments of the recombinant amylase and immunoprecipitation, the major binding protein of CS-1036 in rats was identified as salivary amylase ( K D 5.64 nM). CS-1036 also showed concentration-dependent and saturable binding to human salivary and pancreatic amylase, with similar binding affinity in rats. However, the protein binding of CS-1036 was constant in human plasma (≤10.2%) due to the lower serum amylase level compared with rats and monkeys. From the calculation of the unbound fraction (fu) in plasma based on in vitro K D and B max, the dose-dependent increase in fu after oral administration is speculated to lead to a dose-dependent increase in total body clearance and a high area under the curve/dose at lower doses, such as 0.3 mg/kg in rats. | Purpose. Insulin-like growth factor 1 (IGF-1) is predominantly bound to its specific binding proteins (IGFBPs) in circulating plasma. In the present study, pharmacokinetic analysis of IGF-1 was performed in healthy volunteers to characterize the effect of interactions with IGFBPs on IGF-1 disposition. ::: Methods. Plasma concentration profiles of both free and bound IGF-1 were examined at several doses. An in vitro plasma protein binding was also analyzed. ::: Results. The total body clearance (CLtotal) for the free IGF-1 was much higher than the creatinine clearance, suggesting that the major elimination pathway is by a route other than renal glomerular filtration. The CLtotal for the free IGF-1 exhibited a dose-dependent reduction whereas that for the sum of unbound and bound IGF-1 increased on increasing the dose. The data obtained fitted closely a one-compartment model that involved the binding and dissociation of IGF-1, as well as its biosynthesis and elimination. The estimated parameters suggest that IGF-1 exhibits high affinity binding to IGFBPs, the rate-limiting step in the overall elimination being the dissociation from IGFBPs. ::: Conclusions. The saturation of both the plasma protein binding and elimination accounts for the nonlinear pharmacokinetic profile. The binding to IGFBPs markedly limits both the distribution and elimination of IGF-1. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,643 |
Eighty patients undergoing elective thoracotomy were studied to assess the possibility of predicting arterial oxygenation (PaO2) during one-lung anaesthesia (OLA). The first 50 patients were studied retrospectively. The method of multiple linear regression was used to construct a predictive equation for PaO2 during OLA. Potential predictors of PaO2 during OLA which were considered were: age, side of operation, preoperative pulmonary flow rates, preoperative and intraoperative PaO2 during two-lung ventilation. The three most significant predictors for PaO2 during OLA were: side right of operation (P < 0.05), preoperative FEV1% (P < 0.01) and intraoperative PaO2 during two-lung ventilation (P = 0.0001). The predictive equation for PaO2 after ten minutes of OLA was: PaO2 = 100 - 72 (side) - 1.86 (FEV1%) + 0.75 (two-lung) PaO2; (for side insert 0 for left-sided thoracotomy and 1 for right-sided thoracotomy). The remaining 30 patients were studied prospectively and the predicted PaO2 correlated with the observed PaO2 after ten minutes of OLA (r = 0.73, P < 0.01). Four of 30 patients had a predicted PaO2 at ten minutes of OLA < 150 mmHg. Of these, 2/4 subsequently required abandonment of OLA for pulse oximetric saturation < 85%. We conclude that although it is not possible to predict an individual patient's PaO2 during OLA with a high degree of accuracy, it is possible, before the initiation of OLA, to identify those patients whose arterial oxygenation is likely to decrease to low levels during OLA. | Over the past few decades, major surgical procedures involving the thorax have become commonplace at most larger medical facilities. Advances in perioperative care have allowed surgeons to perform increasingly complex procedures. These procedures are being performed on more seriously ill patients who are at increased risk for significant complications. Recent advances should help the anesthesiologist avoid some of the pitfalls in managing these complex patients. Preoperative assessment aids in the identification of patients at highest risk for intraoperative and postoperative events. Particular attention is given to myasthenia gravis, as thymectomy is among the most common surgical procedures that are performed in these patients. Aggressive pain control techniques, including neuraxial opioids and patient-controlled analgesia, where appropriate, not only improve patient comfort but can improve postoperative pulmonary function. Advances in techniques for providing one-lung ventilation allow the anesthesiologist more options to individualize management for each clinical scenario. Careful fluid management may help to minimize the risk of postoperative pulmonary complications. A basic understanding of video-assisted thoracic surgery should help the anesthesiologist provide optimal surgical conditions and perioperative care. Recent advances demand a greater role for the anesthesiologist if the best outcomes are to be achieved in patients undergoing thoracic procedures. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,644 |
Objective. To quantify in patients with systemic sclerosis (SSc) the absolute nailfold capillary number/mm (the absolute number of capillaries, observable in the first row, in 1 mm per field) and fingertip blood perfusion (FBP) during longterm therapy with the endothelin receptor antagonist bosentan (BOSE) and the synthetic analog of prostacyclin PGI2 iloprost (ILO) by multiple diagnostic tools. Observed values were correlated with clinical outcomes. ::: ::: Methods. Thirty patients with SSc already receiving intravenous ILO (80 μg/day) for 5 continuous days (every 3 mos) were recruited in the clinic. Fifteen patients continued such treatment (ILO group), while in 15 patients BOSE (125 mg twice/day) was added (ILO + BOSE group) because of the onset of pulmonary arterial hypertension or digital ulcers (DU). The followup period was 4 years (T0–T4). Every year the following were evaluated: absolute nailfold capillary number/mm by nailfold videocapillaroscopy, FBP by laser Doppler flowmetry, DU incidence, DLCO, systolic pulmonary arterial pressure (sPAP), renal arterial resistive index, and other biomarkers. From T2 to T4, laser speckled contrast analysis was added. Nonparametric tests were used for statistical analysis. ::: ::: Results. Limited to the ILO + BOSE group, absolute capillary number/mm and FBP showed a progressive increase independently from other variables. In addition, during followup there was a significant reduction (80%) in the incidence of new DU, whereas DLCO and sPAP did not worsen. ::: ::: Conclusion. The study shows in patients with SSc with up to 4 years of combined therapy a progressive significant recovery in structure and function of microvasculature linked to improved clinical outcomes, independent of disease severity. | To identify nailfold videocapillaroscopy (NVC) changes in patients with dermatomyositis (DM) during a 3-year follow-up and to compare the NVC findings between DM and systemic sclerosis (SSc) patients at their first visit. Retrospective study of 24 DM and 24 SSc patients, matched for age and disease duration at first NVC. Capillaroscopic patterns/scores and clinical parameters had been yearly assessed. Nineteen out of 24 DM patients (79%) showed a NVC "scleroderma-like pattern." No statistically significant variation of all the capillaroscopic scores was observed during the 3-year follow-up. By comparing DM patients with or without anti-Jo-1 positivity, no statistically significant difference of the scores of the main capillary parameters was observed at baseline between the groups. Comparing at baseline DM with SSc patients, the giant capillary and microhemorrhage scores were significantly higher in SSc than those in DM patients (p = 0.04 and p = 0.05, respectively), while capillary density, ramification (abnormally shaped capillaries, expression of angiogenesis), and disorganization scores were higher in DM patients (p = 0.05, p = 0.002, p = 0.004, respectively). The absolute number of ramified capillaries was significantly higher in DM patients (p = 0.002), while the absolute capillary number was significantly higher in SSc patients (p = 0.05) at baseline. This pilot study demonstrates, for the first time, over long-term, that the capillaroscopic manifestations of DM persist in contrast to the progressive changes described in SSc patients, and the anti-Jo-1 positivity does not seem to modify the NVC pattern. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,645 |
AIM ::: Viral respiratory infections and atopy have been implicated in the pathogenesis of adenotonsillar hypertrophy and obstructive sleep apnoea (OSA), but the role of atopy is controversial. We aimed to test our hypothesis that atopy, expressed as physician-diagnosed eczema, was associated with adenotonsillar hypertrophy and OSA among children who snored. ::: ::: ::: METHODS ::: Data on children who snored and were referred for polysomnography were reviewed. The primary outcome measures were adenotonsillar hypertrophy and OSA. ::: ::: ::: RESULTS ::: We analysed data on 855 children with a mean age (±standard deviation) of 6.3 (±2.5) years and median obstructive apnoea-hypopnea index of 2.1 episodes per hour. Of the 855 subjects, 133 (15.6%) had physician-diagnosed eczema, 591 (69.1%) had adenoidal hypertrophy, 605 (70.8%) had tonsillar hypertrophy, 219 (25.6%) were obese and 470 (55%) had OSA. Eczema was not related to adenoidal or tonsillar hypertrophy after adjustment for gender and age, with odds ratios (OR) of 1.00 (95% confidence interval 0.67-1.49; p = 0.98) and 0.88 (95% confidence interval 0.59-1.32; p = 0.54), respectively. Similarly, eczema did not affect OSA frequency after adjustment for adenoidal and tonsillar hypertrophy, obesity, gender and age, with an adjusted OR of 0.82 (0.56-1.21; p = 0.32). ::: ::: ::: CONCLUSIONS ::: Atopy was not related to adenotonsillar hypertrophy or OSA in children who snore. | BACKGROUND ::: Atopic dermatitis (AD) is associated with systemic inflammation and may have a similar pathogenesis as obstructive sleep apnea (OSA). However, to date, studies on the association between AD and OSA are limited. ::: ::: ::: OBJECTIVES ::: This study evaluated the association between OSA and AD in children in a large-scale, population-based cohort. ::: ::: ::: METHODS ::: A total of approximately 120 736 children (<18 years) with newly diagnosed AD and 120 736 age- and sex-matched patients without AD from 2000 to 2007 were identified from Taiwan's National Health Insurance Research Database from 2000 to 2007. The Kaplan-Meier test was used for measuring the cumulative incidence of OSA in each cohort. Cox proportional hazard regression models were used for evaluating the risk of OSA in patients with or without AD between the two cohorts. ::: ::: ::: RESULTS ::: The Kaplan-Meier analysis revealed that the cumulative incidence curves of OSA were significantly higher in patients with AD than in those without AD (log-rank test, P < .001). After adjusting for age, sex, urbanization level, and comorbidities, patients with AD had a higher risk of OSA than those without AD (adjusted hazard ratio = 1.86, 95% confidence interval = 1.43-2.42). Compared with patients without AD, patients with AD exhibited a higher risk of developing OSA, irrespective of underlying comorbidities. ::: ::: ::: CONCLUSION ::: This nationwide, population-based cohort study revealed an increased risk of OSA in children with AD. Therefore, comprehensive evaluation and aggressive risk reduction for OSA are recommended in these patients. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,646 |
Objective To observe cerebral ischemia rats of proliferation and differentiation in reactive astrocytes and neural cell.To explore the possible mechanisms of Scalp-acupuncture(SA) in treating cerebral ischemia.Methods Rat models with middle cerebral artery occlusion(MCAO) were used and 70 models were randomized into model group and SA group(inserting needles along anterior oblique line of vertex-temporal and posterior oblique line of vertex-temporal,soon after when a Han's Electro-Acupuncture Apparatus was connected,selecting "disperse-dense" wave,alternating frequency of 2 Hz and 100 Hz at an intensity level of 2 mA,20min per time,1 time each day) and applied neurological severity score(NSS),double-label immunofluorescence assays in observing changes of Brdu、Brdu+Glial fibrillary acidic protein positive cells in subventricular zone and dentate gyrus.Results(1) On NSS at each phase point: SA group demonstrated obvious decline in NSS at 28d when compared with that of model group(P0.01).(2) By comparison,the number of SA group of Brdu、Brdu+Glial fibrillary acidic protein positive cells in subventricular and dentate gyrus zone is the same as control group at 7d,but significantly higher at 14d and 28d.Conclusions The cerebral ischemia rats led to proliferation and differentiation of reactive astrocytes and neural cell in subventricular and dentate gyrus zone.By developing the proliferation and differentiation of Neural stem cell of MCAO rats,scalp-acupuncture is beneficial for protecting cerebral ischemia. | The aim of this study was to investigate the effect of electroacupuncture (EA) on cell proliferation and its molecular mechanisms. Sixty rats were randomly divided into 5 groups: sham operation control (SC), ischemia control (IC), EA, EA and DMSO injection (ED), EA and U0126 injection (EU). All the groups, with the exception of SC, underwent middle cerebral artery occlusion (MCAO), and DMSO or U0126 was injected into the rat in the ED or EU group 30 min prior to MCAO. Cell proliferation was evaluated by proliferating cell nuclear antigen (PCNA) immunostaining. The changes of cell cycle proteins (cyclin D1, CDK4, cyclin E, CDK2, p21 and p27) and the ERK1/2 pathway activation were examined by RT-PCR and western blot analysis. The results showed that the positive cell numbers of PCNA immunostaining in the EA and ED groups were more than those in the IC group (P<0.05). The mRNA and protein levels of p21 or p27 were obviously increased, however, the mRNA and protein levels of cyclin D1, CDK4, cyclin E and CDK2 were reduced in the IC and EU groups. The findings suggested that EA activates the ERK1/2 signaling pathway to protect brain injury during cerebral ischemia. However, this positive effect of EA can be blocked by U0126. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,647 |
OBJECTIVES ::: To evaluate the efficacy and safety of adalimumab in patients with peripheral spondyloarthritis (SpA) not fulfilling the criteria for ankylosing spondylitis (AS) or psoriatic arthritis (PsA). ::: ::: ::: METHODS ::: 40 patients with active peripheral SpA fulfilling the European Spondyloarthropathy Study Group or Amor criteria but not the criteria for AS or PsA were included in a randomised, double-blind, placebo-controlled clinical trial. Patients were treated 1 : 1 with adalimumab or placebo for 12 weeks, followed by an open label extension up to week 24. Safety and efficacy measurements were performed every 6 weeks, with the patient's global assessment of disease activity at week 12 as the primary endpoint. ::: ::: ::: RESULTS ::: At week 12, the patient's and physician's global assessment of disease activity, swollen joint count, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS) and erythrocyte sedimentation rate improved significantly in the adalimumab group compared with the baseline values and compared with placebo. A similar improvement was seen upon adalimumab treatment from weeks 12 to 24 in the patients originally randomised to placebo, whereas the clinical response was maintained or even augmented at week 24 in the patients who received adalimumab from the start. ASDAS inactive disease and BASDAI50 responses were met in 42% of the adalimumab group versus 0%-5% in the placebo group at week 12 (p=0.001 and p=0.008, respectively), and were further increased at week 24. The number of adverse events was not different between the adalimumab and placebo groups. ::: ::: ::: CONCLUSIONS ::: Adalimumab appears to be effective and well tolerated in SpA patients with peripheral arthritis, also in those patients not fulfilling the AS or PsA criteria. | The review presents the recent rapid expansion of therapeutical options in spondyloarthritis. Additionally, it focuses on the importance of additional questions raised by the growing therapeutic possibilities related to the optimal use of these drugs. The emergence of new treatment options opens new avenues and opportunities for treating patients with nonresponse, contraindications, or intolerance for classic drugs. However, it becomes more relevant than ever to define not only drugs and treatment options but also treatment strategies. We address current literature and remaining questions on strategies such as early intervention, combination treatment, personalized medicine, and treat-to-target. Not only the treatment as such, but also the treatment strategy is crucial to reveal the full therapeutic potential and benefit for patients. Whereas cautious but crucial steps have been taken in the last years to explore these aspects, related to timing and sequence of treatment (including combination treatments), stratified medicine approaches, and treat-to-target strategies, it is now time for full-scale investment in prospective strategy trials | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,648 |
Introduction The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line treatment of advanced EGFR mutation–positive NSCLCs. Afatinib and gefitinib costs and patients' outcomes in France were assessed. Methods A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus gefitinib for EGFR mutation–positive NSCLCs. Outcomes and safety were taken primarily from the LUX-Lung 7 trial. Resource use and utilities were derived from that trial, an expert-panel questionnaire, and published literature, limiting expenditures to direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated over a 10-year time horizon for the entire population, and EGFR exon 19 deletion or exon 21 L858R mutation (L858R) subgroups. Deterministic and probabilistic sensitivity analyses were conducted. Results For all EGFR mutation–positive NSCLCs, the afatinib-versus-gefitinib ICER of was €45,211 per quality-adjusted life-year (QALY) (0.170 QALY gain for an incremental cost of €7697). ICERs for EGFR exon 19 deletion and L858R populations were €38,970 and €52,518, respectively. Afatinib had 100% probability to be cost-effective at a willingness-to-pay threshold of €70,000/QALY for patients with common EGFR mutations. Conclusion First-line afatinib appears cost-effective compared with gefitinib for patients with EGFR mutation–positive NSCLCs. | Nivolumab plus ipilimumab improves overall survival and is associated with less toxicity compared with sunitinib in the first-line setting of advanced renal-cell carcinoma (RCC). The current study aimed to assess the cost-effectiveness of nivolumab plus ipilimumab for first-line treatment of advanced RCC from the payer perspectives high- and middle-income regions. A decision-analytic model was constructed to evaluate the health and economic outcomes of first-line sunitinib and nivolumab plus ipilimumab treatment associated with advanced RCC. The clinical and utility data were obtained from published reports. The cost data were acquired for the payer perspectives of the United States (US), United Kingdom (UK), and China. Sensitivity analyses were performed to test the uncertainties of the results. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were used. Nivolumab plus ipilimumab gained 0.70–0.76 QALYs compared with sunitinib. Our analysis determined the following ICERs for nivolumab plus ipilimumab over sunitinib in first-line advanced RCC treatment: US $ 85,506 /QALY; UK $ 126,499/QALY; and China $ 4682/QALY. Sensitivity analyses found the model outputs to be most affected for body weight and for the prices of nivolumab, sunitinib and ipilimumab. Nivolumab plus ipilimumab as first-line treatment could gain more health benefits for advanced RCC in comparison with standard sunitinib, which is considered to be cost-effective in the US and China but not in the UK. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,649 |
Aim ::: Multiple interacting pathways contribute to progression of renal and cardiac damage in chronic kidney disease followed by chronic heart failure (renocardiac syndrome). We hypothesized that simultaneous pharmacological modulation of critical pathways implicated in renocardiac syndrome would effectively reduce fibrosis in and preserve function of heart and kidney. ::: ::: Methods ::: Rats were subjected to subtotal nephrectomy followed 9 weeks later by coronary artery ligation. From week 11 until week 16, rats received vehicle or losartan, or a combination of the NF-kB inhibitor PDTC, the NO donor molsidomine and superoxide dismutase mimetic tempol, or a combination of all four of these plus metoprolol together. At week 16, renal and cardiac structure, function and gene expression were assessed. ::: ::: Results ::: Individual and combined treatments were similarly effective in limiting cardiac fibrosis and further decline in systolic function. Combined treatment with all five drugs reduced renal fibrosis and CTGF gene expression more effectively than other strategies. Combining all five drugs reduced heart rate, inotropy and mean arterial pressure (MAP). ::: ::: Conclusion ::: Thus, in our model of chronic renocardiac syndrome, combined treatments similarly decreased cardiac fibrosis and stabilized systolic function as losartan alone, perhaps suggesting a dominant role for a single factor such as angiotensin II type 1 (AT1) receptor activation or inflammation in the network of aberrant systems in the heart. However, tubulointerstitial fibrosis was most effectively reduced by a five-drug regimen, pointing to additive effects of multiple pathophysiological pathways in the kidney. | Several surgical approaches are being used to induce myocardial ischemia in rats. The present study investigated two different operative procedures in spontaneously breathing and mechanically ventilated rats under sham conditions. A snare around the left coronary artery (LCA) was achieved without occlusion. Left lateral thoracotomy was performed in spontaneously breathing and mechanically ventilated rats (tidal volume 8 ml/kg) with a respiratory rate of 90 strokes/min at different levels of O2 supplementation (room air and 30, 40, and 90% O2). All animals were observed for 60 min after thoracotomy. Rats operated with exteriorization of the heart through left lateral thoracotomy while breathing spontaneously developed severe hypoxia and hypercapnia despite an intrathoracic operation time of <1 min. Arterial O2 content decreased from 18.7 ± 0.5 to 3.3 ± 0.9 vol%. Lactate increased from 1.2 ± 0.1 to 5.2 ± 0.3 mmol/l. Significant signs of ischemia were seen in the electrocardiogram up to 60 min. Mechanically ventilated animals exhibited a spectrum ranging from hypoxia (room air) to hyperoxia (90% O2). In order not to jeopardize findings in experimental myocardial ischemia-reperfusion injury models, stable physiological parameters can be achieved in mechanically ventilated rats at an O2application of 30-40% at 90 strokes/min. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,650 |
Purpose of review This review will provide an update on the use of antimuscarinics, in combination with an α-blocker, in men with an overactive bladder and summarize the efficacy and safety of these drugs in this patient population. Recent findings Studies have included a number of antimuscarinic agents (tolterodine, oxybutynin, propiverine, and solifenacin), with or without an α-blocker. These studies suggest that in men with persistent storage symptoms (overactive bladder symptoms), clinically meaningful improvements can be achieved by addition of an antimuscarinic therapy to an α-blocker. Monotherapy with an antimuscarinic therapy alone in this patient group has proven to be disappointing. Voiding difficulty and acute urinary retention are infrequently reported across all studies, but several trials demonstrated an increase in postvoid residual volume with anticholinergic therapy. It must, however, be borne in mind that reported trials are of short duration (6–12 weeks) and include only men with low postvoid residual volumes at baseline, and the results are, therefore, difficult to unreservedly extrapolate to real-life clinical practice. Summary In a situation in which there are persistent urinary storage symptoms (overactive bladder) following therapy with an α-blocker, the addition of an antimuscarinic therapy is worth considering. A postvoid residual volume should be measured prior to commencing antimuscarinic therapy to rule out baseline retention suggestive of poor detrusor function, and patients should be kept under careful review, particularly, in the early stages of having commenced therapy. | Objective To investigate the safety and efficacy of first-line antimuscarinic monotherapy for men with predominant storage symptoms in the lower urinary tract based on the International Prostate Symptom Score (IPSS) voiding-to-storage subscore ratio (IPSS-V/S). Materials and Methods We conducted a prospective open-label study of first-line tolterodine (4 mg daily) monotherapy in 132 men (age 41–90 years) with a total IPSS (IPSS-T) ≥ 8 and IPSS-V/S ≤ 1. The IPSS storage subscore (IPSS-S), voiding subscore, IPSS-T, quality of life (QoL), maximal flow rate, voided volume, and post-void residual urine (PVR) were evaluated after treatment for 1 month and 3 months. Results The treatment results were satisfactory (global response assessment ≥ 1) in 103 men (78.0%). Mean IPSS-T, IPSS-S, nocturnal frequency, and QoL improved significantly. No patient developed acute urinary retention. However, mean PVR increased significantly (from 51.8 to 63.9 mL), especially among patients older than 70 years. The treatment results did not differ significantly between patients with a total prostate volume (TPV) ≥ 30 mL and those with TPV Conclusion First-line antimuscarinic monotherapy is safe and effective for men with IPSS ≥ 8 and IPSS-V/S ≤ 1. The treatment results were similar in men with TPV larger or smaller than 30 mL. However, we recommend that first-line antimuscarinic monotherapy in men older than 70 years should be administered with caution. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,651 |
Treatment and prevention strategies for wound management have evolved in the past decade and now make it possible for physicians to successfully manage wounds in the residential setting. Wound healing is a multifaceted problem that requires comprehensive medical management and a multidisciplinary approach (Table 1). Improperly managing wounds can result, and increasingly has resulted, in a significant risk management dilemma in long-term care. “I am constantly amazed at the number of patients who were referred to me who simply need basic wound debridement that could have been performed in the residential setting,” said David K. Cobb, MD, medical director, the Wound Healing Clinic, Poudre Valley Hospital, Ft. Collins, CO. Dr. Cobb outlined the current strategies for the treatment of chronic and nonchronic wounds, as well as new insight into the physiological stress response to a wound and the effect of loss of lean body mass on the healing process. “Nutrition issues are at the core of half of the growing number of malpractice lawsuits against nursing homes,” said Deborah Warner, MS, ARNP, LHRM, CWCN, CLC, legal regulatory consultant, Warner Options, Inc., Brandon, FL. Warner emphasized that documentation is critical and noted that not all pressure ulcers are preventable and curable. Therefore, it remains critical for the medical record to accurately reflect the resident’s condition and the plan of care. “The medical record should demonstrate overall what occurred to that resident, what plans were implemented, and what the outcomes were,” she advised. Warner also stressed that good clinical practice and documentation of that practice will become even more important with pending proposed changes in nursing home survey guidelines for pressure ulcer management. | OBJECTIVE ::: To evaluate blood and serum markers in traumatic spinal cord injured (SCI) patients, with and without pressure sores. ::: ::: ::: METHODS ::: This cross-sectional study was performed at the Ministry of Health Diskapi Yildirim Beyazit, and Numune Education and Research Hospitals, Ankara, Turkey, from 2006-2008. A total of 23 SCI patients with pressure sores (group I) and a control group of 25 SCI patients without pressure sores (group II) were evaluated. Characteristics of sores were examined with respect to duration, location, grade, tissue types, surface area, and exudate amount. Recorded laboratory parameters included erythrocyte sedimentation rates (ESR), C-reactive protein (CRP), hemoglobin (Hb), hematocrit (Htc), lymphocytes, white blood cells (WBC), red blood cells (RBC), serum iron, transferrin, total iron-binding capacity (TIBC), ferritin, total protein, albumin, vitamin B12, and zinc. ::: ::: ::: RESULTS ::: The most common pressure sore location was the sacrum (38%). Compared to the control group, the patients with pressure sores showed anemia with reduced serum iron, transferrin, TIBC, and increased ferritin. They also had increased ESR, CRP, and WBC and reduced lymphocytes, total protein, albumin and zinc. Statistically significant correlations were found between CRP, Hb, Htc, lymphocytes, RBC, WBC, and serum protein levels, and grade of pressure sores. ::: ::: ::: CONCLUSION ::: Clinicians should regularly screen patients with respect to blood and serum markers, in order to determine any risks for pressure sores, and they should perform immediate preventive measures based on the patient's condition. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,652 |
Rotator cuff tear causes a high rate of morbidity. After surgical repair, the presence of a scar tissue reduces tendon biomechanical properties. Emerging strategies for enhancing tendon healing are growth factors, cytokines, gene therapy and tissue engineering. However their efficacy has to be proved. Growth factors help the process of tendon healing by aiding cells chemotaxis, differentiation and proliferation. Numerous growth factors, including the bone morphogenetic proteins and platelet-derived growth factor can be found during the early healing process of a rotator cuff repair. Growth factors are delivered to the repair site using tissue-engineered scaffolding, coated sutures, or dissolved in a fibrin sealant. Platelet-rich plasma is an autologous concentration of platelets and contains an high density of growth factors. There is some evidence that platelet-rich plasma may improve pain and recovery of function in a short time period, but it does not improve healing rates in rotator cuff. Thus the routine use of platelet-rich plasma in rotator cuff repair is not recommended. The addition of mesenchymal stem cells to scaffolds can lead to the production of a better quality healing tissue. Gene therapy is a gene transfer from a cell into another, in order to over-express the gene required. In this way, cultures of stem cells can over-express growth factors. Better understanding of the mechanisms of physiological tendon healing can promote the correct use of these new biological therapies for a better healing tissue. | Objective: The aim of the study was to assess the effect of platelet-rich plasma on arthroscopic doublerow rotator cuff repair. Methods: The study included 60 patients with arthroscopic rotator cuff repair. Thirthy patients (mean age: 57.2±7.4; 16 males and 14 females) underwent arthroscopic double-row repair alone (Group 1), another 30 (mean age: 56.9±6.0; 15 males and 15 females) had an injection of platelet-rich plasma (PRP) (Group 2). The groups were compared with DASH as a primary outcome score and Constant-Murley score, visual analog scale, measurement of active forward flexion, and external and internal rotation as secondary outcome measures. Magnetic resonance imaging was used to assess the integrity of the repair at 12 months postoperatively. Results: Primary and secondary outcome measures statistically improved in both groups postoperatively (p<0.05). Overall mean primary and secondary postoperative outcome measures were not significantly different between the 2 groups. A retear was seen in 9 subjects (30%) in Group 1 and 4 subjects (14%) in Group 2 (p<0.05). Conclusion: The local injection of PRP into a primary arthroscopic double-row cuff repair resulted in lower recurrence rates than repairs without the novel biological augmentation material. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,653 |
: An allogeneic cultured dermal substitute (CDS) was prepared by cultivating fibroblasts on a two-layered spongy matrix of hyaluronic acid (HA) and atelo-collagen (Col). The ability of fibroblasts to secrete cytokines is dependent on the conditions of freezing and thawing. The first experiment was designed to investigate the effects of supplements in a cryoprotective medium, that is, dimethylsulfoxide (DMSO), glycerol, and fetal bovine serum (FBS). In each experiment we measured the cell viability after thawing and the cell growth in CDS recultured after thawing. In addition, the amount of vascular endothelial growth factor (VEGF) released from the CDS recultured for one week after thawing was measured. The highest values of cell viability, cell growth, and the amount of VEGF released were obtained when CDS was frozen in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% DMSO and 40% FBS, and then thawed quickly in a water bath at 37°C. However, due to the high cost of FBS, in clinical applications CDS is usually frozen in DMEM supplemented with 10% DMSO and 20% FBS. In practice, however, physicians often cannot use CDS immediately after thawing, depending on clinical conditions. Therefore, in the second experiment we investigated cell viability at different time points after thawing. In addition, we investigated cell growth and the amount of VEGF released from fibroblasts in CDS at different time points after thawing under different conditions, and after further reculturing for one week. We recommend that CDS be rinsed with lactated Ringer's solution immediately after thawing, and that it be used within 4 h after thawing. | In a general wound healing process, foreign bodies and tissue detritus have to be broken down and then a new tissue is produced. However, the new tissue formation sometimes fails to proceed under the impaired conditions such as burn injury and intractable skin ulcer. A major obstruction to wound healing is infection. Another obstruction to wound healing is deficiency of growth factors. The endogenous levels of growth factors are reduced in some chronic wounds. To improve these wound conditions, researchers have been trying to create several types of artificial skins. The tissue-engineered products include three prime constituents, i.e., cells, growth factors, and materials. In this review, the practical design of tissue-engineered products for skin regenerative medicine is introduced. The first design makes it possible to release silver sulfadiazine (AgSD) from a wound dressing. The second design makes it possible to release Epidermal Growth Factor (EGF) from a wound dressing or a skin care product composed of hyaluronic acid spongy sheet containing bioactive ingredients. The third design makes it possible to release several types of growth factors from allogeneic fibroblasts within cultured dermal substitute. This tissue-engineered product is prepared by seeding allogeneic fibroblasts into a collagen and hyaluronic acid spongy sheet. Although allogeneic cells are rejected gradually in immune system, they are able to release some types of growth factors, thereby regenerating a damaged tissue. The clinical study demonstrates that these tissue-engineered products are promising for the treatment of burn injury and intractable skin ulcer. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,654 |
The spontaneously hypertensive rat (SHR) has enhanced tubuloglomerular feedback (TGF) responses and diminished buffering by juxtaglomerular apparatus (JGA)-derived nitric oxide (NO) despite enhanced expression of NO synthase (NOS) isoforms in the JGA. We tested the hypothesis that the enhanced TGF response is due to inactivation of NO by oxygen radicals (O(-)(2)). SHR had significantly (P<0.05) greater expression of the peroxynitrate reaction product, nitrotyrosine, in renal cortex. A membrane-permeant, metal-independent superoxide dismutase mimetic, tempol, was used to test the functional role of O(-)(2). Maximum TGF responses, assessed from changes in proximal stop-flow pressure (P(SF)) during orthograde loop of Henle (LH) perfusion of artificial tubular fluid (ATF), were enhanced in SHR [Wistar-Kyoto rat (WKY) 8.8+/-0.4 (n = 30 nephrons) vs. SHR 10.8+/-0.4 mm Hg (n = 39 nephrons), P<0.001]. TGF responses of SHR were unresponsive to microperfusion of 7-nitroindazole (7-NI, 10(-4) M), which is an inhibitor of neuronal NOS (nNOS) [WKY 8.3+/-0.3 to 10.8+/-0.4 (n = 8, P<0.001) vs. SHR 10.0+/-0.7 to 10.5+/-0.8 mm Hg (n = 8; not significant)]. Microperfusion of tempol (10(-4) M) into the efferent arteriole (EA) supplying the peritubular capillaries (PTC) blunted TGF. The response to tempol was significantly (P< 0.05) greater in SHR [DeltaTGF in WKY 19+/-6% (n = 10) vs. SHR 32+/-3% (n = 10)]. Microperfusion of the NO donor compound S-nitroso-N-acetyl-penicillamine (SNAP, 10(-7)-10(-4) M) via the LH blunted TGF, but the sensitivity of the response was impaired significantly (P<0.05) in SHR nephrons. PTC perfusion of tempol (10(-4) M) normalized the response to loop perfusion of both SNAP and 7-NI in SHR nephron to levels in WKY (during tempol, DeltaP(SF) with 7-NI in WKY 8.9+/-0.6 to 11.4+/-0.8; n = 12 vs. SHR 9.5+/-0.5 to 12.5+/-0.4 mm Hg; n = 16). In conclusion, TGF responses are enhanced in SHR, in part due to a diminished role for NO from nNOS in blunting TGF due to enhanced O(-)(2) formation. O(-)(2) in the JGA enhances TGF responses by inactivation of locally generated NO. | Nitric oxide (NO) is an important molecular mediator of numerous physiological processes in virtually every organ. In the kidney, NO plays prominent roles in the homeostatic regulation of glomerular, vascular, and tubular function. Differential expression and regulation of the NO synthase (NOS) gene family contribute to this diversity of action. This review explores recent advances in the molecular and cell biology of the NOS isoforms and relates these findings to functions of NO in the control of normal renal hemodynamics, the glomerular microcirculation, and renal salt excretion. Newly recognized molecular diversity of the NOS gene products, factors governing NOS isozyme gene expression and catalytic activity, and the intrarenal distribution of the NOS isoforms are examined. Physiological data regarding the complex roles of NO in the control of renal hemodynamics and the glomerular microcirculation are analyzed, and the effects of chronic NOS inhibition on glomerular function and structure are presented. The contributions of NO to renal salt excretion as well as functional and molecular biological evidence for adaptive changes in NOS isoform expression during variations in dietary salt balance are discussed. Current investigative challenges and goals for future research of renal NO biology are presented. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,655 |
High pressure, low temperature Raman measurements performed on LaMnO3 up to 34 GPa provide the first experimental evidence for the persistence of the Jahn-Teller distortion over the entire stability range of the insulating phase. This result resolves the ongoing debate about the nature of the pressure driven insulator to metal transition (IMT), demonstrating that LaMnO3 is not a classical Mott insulator. The formation of domains of distorted and regular octahedra, observed from 3 to 34 GPa, sheds new light on the mechanism behind the IMT suggesting that LaMnO3 becomes metallic when the fraction of undistorted octahedra domains increases beyond a critical threshold. | The microstrains in heavy-ion irradiated manganite LaMnO3 can be managed in linear response of irradiation dose, and the corresponding internal pressure up to 8 GPa can be induced by varying doses. The response of structure under stress is studied by means of Density Functional Theory and Lattice Dynamic Calculation. All obtained Raman scattering lines are discussed in details to shed light onto structural changes during ion implantation. There appears new resonance peak at around 550 cm-1, which splits from broad features in the spectra, and attributes to the anti-symmetric vibrations of O6 cages. The blue shift of this peak scales to ~2.4 cm-1 per 1 GPa of stress. Another strong feature showing considerable blue shift is seen in the vicinity of 640 cm-1 and corresponds to one of rhombohedral distortion related soft modes. A weak mode, not frequently reported, is seen at around 420 cm-1 and corresponds to translation-like motions of fixed O6 cages. | We determined effects of the vasopeptidase inhibitor (VPI) omapatrilat and angiotensin II type 1 receptor (AT1R) blocker (ARB) candesartan in rats during healing between day-2 and day-21 after reperfused myocardial infarction (RMI) on left ventricular (LV) remodeling and function, and regional matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP (TIMP)-3, inducible-nitric-oxide-synthase (iNOS), oxidant-generating myeloperoxidase (MPO), and cytokines tumor-necrosis-factor (TNF)-α, interleukin (IL)-6 and IL-10, and transforming-growth-factor (TGF)-β1, and collagens. Compared to RMI-placebo, both agents reversed adverse LV remodeling and systolic and diastolic dysfunction, improved collagen remodeling, and normalized MMP-9 (activity, protein, and mRNA), TIMP-3 (protein and mRNA), and iNOS, MPO, TNF-α, IL-6, and TGF-β1 proteins, and improved MMP-9/TIMP-3 balance and IL-10 levels in previously ischemic zones. The results suggest that modulation of matrix proteases, oxidants, cytokines, and NOSs with omapatrilat and candesartan contribute to reversal of adverse collagen and LV remodeling and attenuation of LV dysfunction during healing after RMI. | eng_Latn | 22,656 |
RATIONALE AND OBJECTIVES ::: Non-flow-dependent myocellular accumulation and uptake kinetics of the myocardial perfusion and viability imaging agent, hexakis (2-methoxyisobutyl isonitrile) technetium 99m(I) (Tc-SESTAMIBI), are thermodynamically driven by large negative sarcolemmal and mitochondrial membrane potentials, and can be enhanced by addition of the lipophilic anion, tetraphenylborate (TPB). To further understand the general properties required of a co-administered compound for increasing the kinetic response of Tc-SESTAMIBI to membrane potential, a systematic appraisal of additional candidate lipid-soluble anions and neutral dipolar compounds was undertaken. ::: ::: ::: METHODS ::: Each compound was biologically tested for its ability to enhance Tc-SESTAMIBI accumulation in a cultured heart cell model, and electronic dipole moments were evaluated using semi-empirical molecular orbital calculations. ::: ::: ::: RESULTS ::: Of this series, phloretin (100 microM), TPB (10 microM), and to a lesser degree, 8-anilino-1-naphthalene sulfonate (100 microM) enhanced myocellular accumulation of Tc-SESTAMIBI. Phloretin enhancement was pH-dependent, showing maximal effect at pH 7.4, and was not additive to the augmentation induced by TPB. A series of additional lipid soluble anions and structural analogues of phloretin were without effect. ::: ::: ::: CONCLUSION ::: Although selected compounds enhanced Tc-SESTAMIBI accumulation, overall, no direct relationship of dipole moment to biologic enhancement was demonstrated. | BACKGROUND/AIM ::: Currently used radiopharmaceuticals are nonspecific and most of them are accumulated by benign tumors as well as inflammatory lesions, abscess or granulomatous lesions. Some factors such as the choice of radiopharmaceutical applied, histopathologic type of tumor, its size, location or previous tumor treatment could influence tumor imaging sensitivity. The aim of this study was to investigate accumulation of 99mTc-methoxy-2-isobutylisonitrile (99mTc-MIBI) by counting early/delayed uptake and release of this radiopharmaceutical inside lung tumors and evaluating possible factors which could be involved in its accumulation. ::: ::: ::: METHODS ::: Two-phase 99mTc-methoxy-2-isobutylisonitrile single photon emission computed tomography scan (early and delayed scan) was performed in 60 patients with lung tumors (the group 1 - 30 benign, and the group 2 - 30 malignant tumors). We calculated the uptake ratio on early (early ratio - ER), delayed images (delayed ratio - DR) and retention index (RI). Individual influence of etiology, diameter, localization, and histological type on uptake/release values was evaluated with regression analysis. ::: ::: ::: RESULTS ::: The values of ER and DR were significantly different in both groups (p < 0.01), showing lower values in benign vs malignant lung tumors (ER 1.36 ± 0.094 and DR 1.25 ± 0.089 vs ER = 1.93 ± 0.106 and DR = 1.7 ± 0.095 respectively). Tumor size showed a significant influence on the change of ER and DR values (p < 0.01), with greater uptake in tumors > 3 cm. RI values showed no significance between the two groups (P > 0.05). ::: ::: ::: CONCLUSION ::: The uptake ratio of 99mTc-methoxy-2-isobutylisonitrile could be a useful index in differentiating lung tumors, while RI has no influence on this. Among the evaluated factors, ER and DR values are significantly influenced only by the diameter of lung tumor, while localization or different histological types between the groups has no influence on this. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,657 |
Aim: Vascular leakage following cardiopulmonary bypass contributes to morbidity. Angiopoietin-1 and -2 are biomarkers of endothelial dysfunction. Our aim was to characterize Ang-1 and -2 association with clinical characteristics and outcomes. Methods: Observational cohort study measuring Ang-1/-2 with a panel of cytokines in adults undergoing cardiopulmonary bypass. Results: Ang-2 levels increased immediately postop whereas Ang-1 levels decreased over time. No significant correlation was found with other inflammatory mediators. High correlation was found between the hospital length of stay and Ang-2 increase at 24 h (rho = 0.590; p < 0.0001). The predictors of Ang-2 increase were female gender, cross clamp time, transfusion of blood and absence of angiotensin-converting enzyme inhibitor as a pre-op medication. Conclusion: Angiopoietins can detect vascular leakage early and could impact patient's management to decrease length of stay after cardiac surgery. | The angiopoietin-Tie2 system is an important regulator of vasculogenesis and vascular integrity. Angiopoietin-2 (Ang2) disrupts blood vessel formation in the developing embryo by antagonizing the effects of angiopoietin-1 (Ang1) on the Tie2 receptor. In this study, we examined the effect of a well-known proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), on Ang2 expression in human umbilical vein endothelial cells. Reverse transcriptase-polymerase chain reaction and Northern blot analyses indicated that TNF-alpha induced Ang2 mRNA expression in a time- and dose-dependent manner. Western blot analyses revealed that TNF-alpha treatment increased cellular Ang2 protein. TNF-alpha induced less Ang2 mRNA expression in the presence of nuclear factor-kappaB (NF-kappaB) inhibitor. These results suggest that TNF-alpha-induced inflammatory angiogenesis might be facilitated by the induction of Ang2. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,658 |
The aim of this work was to investigate the production of oxidative damage in homogenized kidney, liver and brain of spontaneously hypertensive rats (SHR), as well as the involvement of angiotensin (Ang) II in this process. Groups of 12-week-old SHR and Wistar Kyoto rats (WKY) were given 10 mg/kg/day losartan in the drinking water during 14 days. Other groups of WKY and SHR without treatment were used as controls. The production of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) were determined. No significant difference in TBARS was observed between untreated SHR or WKY rats; GSH content was lower in the liver but higher in the brain of SHR compared to WKY rats. In tissues from the SHR group, SOD and Gpx activities were reduced, whereas CAT activity was slightly increased in kidney. TBARS levels did not change in WKY rats after losartan administration, but were reduced in SHR liver and brain. Losartan treatment decreased GSH content in WKY kidney, but increased GSH in SHR liver. The activity of the antioxidant enzymes was not modified by losartan in WKY rats; however, their activities increased in tissues from treated SHR. The lower activity of antioxidant enzymes in tissues from hypertensive rats compared to those detected in normotensive controls, indicates oxidative stress production. Ang II seems to play no role in this process in normotensive animals, although AT1 receptor blockade in SHR enhances the enzymatic activity indicating that Ang II is implicated in oxidative stress generation in the hypertensive animals. | Increased production of free radicals and impairment of mitochondrial function are important factors in the pathogenesis of hypertension. This study examined the impact of hypertension on mitochondrial respiratory chain function, coenzyme Q(9) (CoQ(9)), coenzyme Q(10) (CoQ(10)), and alpha-tocopherol content in brain mitochondria, and the effect of blockade of angiotensin II type 1 receptors (AT1R) in the prehypertensive period on these parameters. In addition, blood pressure, heart and brain weight to body weight ratios, and the geometry of the basilar artery supplying the brain were evaluated. In the 9th week blood pressure and heart weight/body weight ratio were significantly increased and brain weight/body weight ratio was significantly decreased in spontaneously hypertensive rats (SHR) when compared to Wistar rats (WR). The cross-sectional area of the basilar artery was increased in SHR. Glutamate-supported respiration, the rate of ATP production, and concentrations of CoQ(9), CoQ(10), and alpha-tocopherol were decreased in SHR. The succinate-supported function and cytochrome oxidase activity were not changed. The treatment of SHR with losartan (20 mg/kg/day) from 4th to 9th week of age exerted preventive effect against hypertension, heart and arterial wall hypertrophy, and brain weight/body weight decline. After the therapy, the rate of ATP production and the concentration of CoQ increased in comparison to untreated SHR. The impairment of energy production and decreased level of lipid-soluble antioxidants in brain mitochondria as well as structural alterations in the basilar artery may contribute to increased vulnerability of brain tissue in hypertension. Long-term treatment with AT1R blockers may prevent brain dysfunction in hypertension. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,659 |
Sliced portions of the walls of human aortic aneurysms were incubated with extracts of human plasma and serum to determine the profile of prostanoid production. 6-Oxo-prostaglandin (PG) F1 alpha, PGE2, PGF2 alpha, and thromboxane (TX) B2 were measured by gas chromatography/electron capture mass spectrometry. 6-Oxo-PGF1 alpha, the stable hydrolysis product of PGI2, was the major cyclooxygenase product but substantial amounts of TXB2 (the hydrolysis product of TXA2), with smaller amounts of PGE2 and PGF2 alpha were also synthesised. These prostanoids could contribute to the response of the vascular wall to injury, thereby influencing the disease process. Serum extracts stimulated PGI2 and TXA2 synthesis, probably as a result of their Ca2+ content. | BACKGROUNDThe pathogenesis of pulmonary vascular disease in children with congenital heart disease is incompletely understood. Thromboxane (TX) A2 and prostacyclin (PGI2) have opposing effects on platelet aggregation and pulmonary vascular smooth muscle. An imbalance in their biosynthesis could contribute to the progressive increase in pulmonary vascular resistance seen in older untreated patients with pulmonary hypertensive congenital heart disease and the thrombotic complications they may develop.METHODS AND RESULTSWe investigated TXA2 and PGI2 biosynthesis in 15 young children (0.2 to 2.25 years old) with congenital heart disease with increased pulmonary blood flow and potentially reversible pulmonary vascular disease by measuring urinary excretion of 2,3-dinor-TXB2 and 2,3-dinor-6-oxoprostaglandin (PG) F1 alpha and compared the findings with those in 16 healthy children (0.5 to 2.8 years old). 2,3-Dinor-TXB2 excretion was greater in the patients than in control subjects (1253 +/- 161 versus 592 +/- 12... | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,660 |
The amount of lymph node dissection (LD) required during surgical treatment of gastric cancer surgery has been quite controversial. In the 1970s and 1980s, Japanese surgeons developed a doctrine of aggressive preventive gastric cancer surgery that was based on extended (D2) LD volumes. The West has relatively lower incidence rates of gastric cancer, and in Europe and the United States the most common LD volume was D0-1. This eventually caused a scientific conflict between the Eastern and Western schools of surgical thought: Japanese surgeons determinedly used D2 LD in surgical practice, whereas European surgeons insisted on repetitive clinical trials in the European patient population. Today, however, one can observe the results of this complex evolution of views. The D2 LD is regarded as an unambiguous standard of gastric cancer surgical treatment in specialized European centers. Such a consensus of the Eastern and Western surgical schools became possible due to the longstanding scientific and practical search for methods that would help improve the results of gastric cancer surgeries using evidence-based medicine. Today, we can claim that D2 LD could improve the prognosis in European populations of patients with gastric cancer, but only when the surgical quality of LD execution is adequate. | BACKGROUND ::: Radical gastrectomy with D2 lymph node (LN) dissection is the standard surgical procedure for patients with resectable gastric cancer (GC). In the fifteenth edition of the Japanese Classification of Gastric Carcinoma, the 14v LN (LNs along the root of the superior mesenteric vein) was defined as the regional gastric LN. The efficacy of 14v LN dissection during radical distal gastrectomy for lower-third GC remains controversial. ::: ::: ::: AIM ::: To analyze whether the addition of 14v LN dissection improved the survival of patients with lower-third GC. ::: ::: ::: METHODS ::: The data from 65 patients who underwent 14v LN dissection and 65 patients treated without 14v LN dissection were selected using the propensity score-matched method from our institute database constructed between 2000 and 2012. Overall survival was compared between the groups. ::: ::: ::: RESULTS ::: Overall survival was similar between patients with 14v LN metastasis and those with distant metastasis (P = 0.521). Among patients with pathological stage IIIA disease, those who were treated with 14v LN dissection had a significantly higher overall survival than those treated without it (P = 0.020). Multivariate analysis showed that age < 65 years and pT2-3 stage were independent favorable prognostic factors for prolonged overall survival in patients with pathological stage IIIA disease. Patients with No. 1, No. 6, No. 8a, or No. 11p LN metastasis were at higher risk of having 14v LN metastasis. ::: ::: ::: CONCLUSION ::: Adding 14v LN dissection to D2 dissection during radical distal gastrectomy may improve the overall survival of patients with pathological stage IIIA lower-third GC. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,661 |
Garlic has been used in herbal medicine for thousands of years. Some reports have shown that garlic has protective effects against atherosclerosis and inhibits platelet function. In this study, we investigated the mechanism by which diallyl trisulfide (DT), a component of garlic, inhibits platelet function. DT inhibited platelet aggregation and Ca(2+) mobilization in a concentration-dependent manner without increasing intracellular cyclic AMP and cyclic GMP. DT also had no inhibitory effects on thromboxane A(2) (TXA(2)) production in cell-free systems. Collagen-related peptide (CRP)-induced Ca(2+) mobilization is regulated by phospholipase C-gamma2 (PLC-gamma2) activation. We evaluated the effect of DT on tyrosine phosphorylation of PLC-gamma2 and the production of inositol-1,4,5-trisphosphate (IP(3)). DT at concentrations that inhibited platelet aggregation and Ca(2+) mobilization had no effects on tyrosine phosphorylation of PLC-gamma2 or on the formation of IP(3) induced by CRP. Similar results were obtained with thrombin-induced platelet activation. DT inhibited platelet aggregation and Ca(2+) mobilization induced by thrombin without affecting the production of IP(3.) We then evaluated the effect of DT on the binding of IP(3) to its receptor. DT at high concentrations partially blocked the binding of IP(3) to its receptor. Taken together, our findings suggest that the agent suppresses Ca(2+) mobilization at a step distal to IP(3) formation. DT may provide a good tool for investigating Ca(2+) mobilization. | BACKGROUND ::: In vitro studies suggest that various bioactive constituents of Allium sativum (garlic) inhibit platelet function. The extent, however, to which dietary doses of garlic influence platelet function remains unknown. Therefore, we tested the effect of raw garlic on platelet function using point-of-care monitoring devices sensitive for cyclooxygenase I-inhibition and platelet adhesion. ::: ::: ::: METHODS ::: Whole blood from 18 healthy volunteers was investigated before and 5 h after ingestion of the study medication consisting of Greek tsatsiki with 4.2 g raw garlic (verum), or Greek tsatsiki without garlic (placebo), in a randomized, crossover, observer-blinded, placebo-controlled study. The potential long-term effects of garlic were investigated in five volunteers after daily ingestion of 4.2 g of raw garlic over 1 wk. Platelet function was assessed with the Platelet Function Analyzer (PFA-100), impedance aggregometry (Multiplate), and thrombelastographic Platelet Mappingtrade mark. In vitro experiments were performed to prove the sensitivity of the assays to garlic-induced platelet inhibition. ::: ::: ::: RESULTS ::: Baseline values of platelet function were within normal range in all volunteers. Platelet function was not impaired by single and repeated oral consumption of Greek tsatsiki containing raw garlic in any point-of-care monitoring test used. ::: ::: ::: CONCLUSIONS ::: Platelet function is not impaired by single and repeated oral consumption of a dietary dose of garlic in healthy volunteers. Dishes containing socially acceptable doses of raw garlic are unlikely to increase the risk of perioperative bleeding. Further studies are warranted to determine the potential additive effects of platelet-inhibiting drugs combined with garlic and other herbs. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,662 |
PURPOSE ::: The purpose of the study is to explore the function of P2X3 and NK1 receptors antagonists on cyclophosphamide (CYP)-induced cystitis in rats. ::: ::: ::: METHODS ::: Sixty female Sprague-Dawley (SD) rats were randomly divided into three groups. The rats in the control group were intraperitoneally (i.p.) injected with 0.9% saline (4 ml/kg); the rats in the model group were i.p. injected with CYP (150 mg/kg); and the rats in the intervention group were i.p. injected with CYP with subsequently perfusion of bladder with P2X3 and NK1 receptors' antagonists, Suramin and GR 82334. Spontaneous pain behaviors following the administration of CYP were observed. Urodynamic parameters, bladder pressure-volume curve, maximum voiding pressure (MVP), and maximum cystometric capacity (MCC), were recorded. Pathological changes in bladder tissue were observed. Immunofluorescence was used to detect the expression of P2X3 and NK1 receptors in bladder. ::: ::: ::: RESULTS ::: Cyclophosphamide treatment increased the spontaneous pain behaviors scores. The incidence of bladder instability during urine storage period of model group was significantly higher than intervention group (χ(2) = 7.619, P = 0.007) and control group (χ(2) = 13.755, P = 0.000). MCC in the model group was lower than the control and intervention groups (P < 0.01). Histological changes evident in model and intervention groups rats' bladder included edema, vasodilation, and infiltration of inflammatory cells. In model group, the expression of P2X3 receptor increased in urothelium and suburothelium, and NK1 receptor increased in suburothelium, while the expression of them in intervention group was lower. ::: ::: ::: CONCLUSIONS ::: In CYP-induced cystitis, the expression of P2X3 and NK1 receptors increased in urothelium and/or suburothelium. Perfusion of bladder with P2X3 and NK1 receptors antagonists ameliorated the bladder function. | Current evidence from clinical and laboratory studies confirms that mast cells play a central role in the pathogenesis and pathophysiology of interstitial cystitis (IC). In this article, we focus on the role of the mast cell in IC and examine the ways in which mast cells and other pathophysiologic mechanisms are interrelated in this disease. Identifying the patients with IC who have mast cell proliferation and activation will enable us to address this aspect of disease pathophysiology in these individuals with targeted pharmacotherapy to inhibit mast cell activation and mediator release. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,663 |
The aims of the present study were to evaluate oxidative status, by investigating the serum Paraoxonase/Arylesterase (PON/ARE) activities along with conjugated dienes in patients with IBS and controls and to confirm the link between oxidative stress and IBS. Thirty IBS patient and 30 healthy subjects were recruited. Total serum cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), PON and ARE activities and conjugated dienes levels were measured. Mean serum PON1 activity was lower in IBS group compared to that of the control group whereas there was no significant difference in ARE activity between IBS and control groups (p < 0.000, p < 0.716, respectively). Serum conjugated diene levels of the IBS group was significantly higher than that of the control group (p < 0.01). The drop in PON activity accompanied with an increase in conjugated diene levels indicate the presence of oxidative stress, a disturbance in prooxidant - antioxidant balance and increased inflammation in IBS patients. | BACKGROUND AND AIMS Post-dysenteric irritable bowel syndrome (PD-IBS) develops in up to 25% of patients following Campylobacter enteritis. Our aim was to define the pathological basis of this subgroup of IBS. METHODS Twenty one patients (group 1) underwent serial rectal biopsy and gut permeability testing following acute Campylobacter enteritis as did 10 PD-IBS patients (group 2) and 12 asymptomatic controls. RESULTS In group 1, enteroendocrine cell (EC) numbers were markedly increased initially and at six and 12 weeks (p r =0.6, p=0.01). At one year, seven subjects (five with persistent loose stools) had rectal biopsies which showed significantly elevated EC, CD3, and IEL counts. In group 2, EC and IEL counts were significantly increased compared with controls (p CONCLUSION Increased EC, T lymphocytes, and gut permeability are acute changes following Campylobacter enteritis which can persist for more than a year and may contribute to PD-IBS. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,664 |
Type 2 diabetes (T2D) is a chronic degenerative disease that involves the participation of several genetic and environmental factors. The objective of the study was to determine the association of the IRS1 (rs1801278), CAPN10 (rs3792267), TCF7L2 (rs7903146 and rs12255372), and PPARG (rs1801282) gene polymorphisms with T2D, in two different Mexican populations. We conducted a case-control replication study in the state of Guerrero and in Mexico City, with 400 subjects from Guerrero and 1065 from Mexico City. Data were analyzed by logistic regression, adjusting by ancestry, age, gender, and BMI, to determine the association with T2D. Heterozygosity for the Gly972Arg variant of the IRS1 gene showed the strongest association for T2D in both analyzed samples (OR = 2.43, 95% CI 1.12-5.26 and 2.64, 95% CI 1.37-5.10, respectively). In addition, an association of two SNPs of the TCF7L2 gene with T2D was observed in both cities: rs7903146, (for Guerrero OR = 1.98 CI95% 1.02-3.89 and for Mexico OR = 1.94 CI95% 1.31-2.88) and rs12255372 (OR = 1.79 CI95% 1.08-2.97, OR = 1.78 CI95% 1.17-2.71 respectively). We suggest that our results provide strong evidence that variation in the IRS1 and TCF7L2 genes confers susceptibility to T2D in our studied populations. | Type 2 diabetes mellitus (T2D) is a main public health problem in the Mexican population. It is characterized by insulin resistance in peripheral tissues and a relative deficiency in the pancreatic β -cell functions. Diverse single nucleotide polymorphisms (SNPs) of the IRS1 gene have been associated with insulin resistance and T2D risk. The aim of this study was to identify the association between known IRS1 polymorphisms (Pro512Ala, Asn1137Asp, Gly972Arg, and Arg158Pro) in a sample of diabetic patients compared with healthy controls selected from Mexico's 2000 National Health Survey, both with normal body mass index (BMI). We identified 444 diabetes cases that were age matched with the same number of controls. Genotypic and allelic frequencies were evaluated, and conditional logistic regression was used to evaluate the association between the SNPs and diabetes risk. Of the 4 SNPs studied, only Gly972Arg showed significant differences between cases and controls, with allele frequency of 2.6% in controls as compared with 7.9% in cases. Subjects with at least 1 copy of the Gly972Arg polymorphism of the IRS1 gene showed a greater risk for diabetes, with a crude odds ratio of 3.26 (95% confidence interval, 2.00-5.33); after adjusting for BMI, age, family history of T2D, and sex, the odds ratio was 2.91 (95% confidence interval, 1.73-4.90). Our results suggest the participation of Gly972Arg polymorphism of IRS1 in the genetic susceptibility to TD2 in Mexican population. The restriction of including only participants with normal BMI might increase the power to detect genetic determinants of T2D. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,665 |
It is well established that oxidative stress is common in inflammatory bowel diseases (IBDs). Accordingly, antioxidants are recommended for treatment. The aim of this study is to compare the effects of antioxidants contained in the various types of tea on symptoms and evolution of IBD and colorectal cancer (CRC). Analysis of the literature revealed that the theaflavin-3, 30-digallate (TFDG) contained in black tea, and epigallocatechin-3-O-gallate (EGCG) contained in green tea have protective effects against oxidative stress. Moreover, these substances are involved in many biochemical processes responsible for inflammation and proliferation of cancer cells. It is documented that both TFDG and EGCG are able to reduce inflammatory phenomena and symptoms associated with IBD, as well as to reduce the proliferation of CRC cells. Most studies are performed in vitro or in experimental animal models. It is, therefore, advisable to formulate studies that could be carried out on humans or human samples, in order to develop the appropriate therapeutic strategies. | Flavonoids are phytochemicals which can regulate the activity of the intestinal immune system. In patients with chronic inflammatory bowel disease (IBD) there is an overexpression and imbalance of the components of the inflammatory immune reactions which are chronically activated. Suppression of inflammation can be achieved by anti-inflammatory drugs which are used in clinical medicine but these can cause serious side effects. Flavonoids can have natural immunosuppressive properties and inhibit the activation of immune cells and its effectors (chemokines, TNF-, cytokines). Phytochemicals such as flavonoids bind to the nuclear Ah (aryl hydrocarbon) -receptor thereby stimulating protective enzyme activities. As shown by clinical evidence in patients and by experimental work some flavonoids (apigenin, epigallocatechin gallate) were effective in the inhibition of inflammation. Instead of or additionally to anti-inflammatory drugs flavonoids can be used in IBD patients to treat the over-reactive immunologic system. This is accomplished by upregulation of the Ah-receptor. Flavonoids interact with toll-like receptors expressing on the surface of immune cells, then they were internalized to the cytosol and transferred into the nucleus, where they were attached to the Ah-receptor. The Ah-receptor binds to the Ah-R nuclear translocator and via Ah response element beneficial protective enzymes and cytokines are induced, leading to upregulation of the anti-inflammatory system. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,666 |
PURPOSE ::: Oxybutynin is used clinically to lower intravesical pressure and detrusor overactivity. In vitro it inhibits stretch induced bladder smooth muscle cell proliferation. We tested whether oxybutynin also prevents hypertrophic bladder changes in vivo in a model of partial bladder obstruction. ::: ::: ::: MATERIALS AND METHODS ::: Subvesical obstruction was induced in immature guinea pigs by a silver ring around the urethra. Eight animals received 0.4 mg oxybutynin per kg body weight per day in 2 doses. Control groups were obstructed without oxybutynin treatment or sham operated. Urodynamic pressure flow studies were performed at 1-week intervals for 10 weeks in all animals under anesthesia with ketamine/xylazine. After 10 weeks the animals were sacrificed and the bladder was removed for structural analysis with periodic acid-Schiff stain, in which the number of glycogen granules was also scored as a measure of previous ischemia. ::: ::: ::: RESULTS ::: Compared to the sham treated group obstructed animals had significantly higher intravesical pressure and detrusor overactivity, lower compliance and increased contractility. Obstructed animals that received oxybutynin retained normal intravesical pressure, detrusor overactivity and compliance. Their bladder contractility increased as in obstructed animals. The oxybutynin group showed less collagen infiltration in the detrusor and fewer glycogen granules compared to those in obstructed animals. ::: ::: ::: CONCLUSIONS ::: Our results demonstrate that oxybutynin has a protective effect on bladder function and structure. Prevention of hypertrophic and ischemic bladder changes is an argument for an early start of oxybutynin treatment in children with inborn neurogenic bladder dysfunction, such as spina bifida, or in patients with urethral valves. | PURPOSE ::: Partial bladder outlet obstruction (PBOO) usually induces overactive bladder (OAB) associated with detrusor overactivity (DO) which is related to the increased contractility of detrusor smooth muscle (DSM). The pharmacological activation of small-conductance Ca2+-activated K+ (SK) channels dramatically attenuates DSM contractility. However, the role of SK channels in the PBOO DSM is less clear. Here, we tested the hypothesis that PBOO is associated with decreased expression and function of SK channels in DSM and that the activation of SK channels is a potential target to regulate DO. ::: ::: ::: METHODS ::: Two weeks after surgically inducing PBOO in female guinea pigs, cystometry indicated that DO was achieved. Using this animal model, we conducted quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and isometric tension recordings. ::: ::: ::: RESULTS ::: The qRT-PCR experiments indicated that PBOO DSM had reduced SK channel mRNA expression. Isometric tension recordings showed a decreased inhibitory effect of NS309 on spontaneous phasic and electrical field stimulation-induced contractions via the activation of SK channels in PBOO DSM. ::: ::: ::: CONCLUSIONS ::: This study presents the novel finding that PBOO is associated with attenuated DSM SK channel expression and function, which results in increased DSM contractility and contributes to DO. Therefore, SK channels could be a therapeutic target to control OAB. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,667 |
The acute chest syndrome is a generic term for pulmonary complications of sickle cell diseases with heterogeneous etiologies that include pneumonia, vaso-occlusion of pulmonary arterioles, rib infarction, and fat embolism syndrome. My review summarizes these etiologies, the evidence, and pathophysiology supporting the hypothesis that infarction of segments of ribs by the same vaso-occlusive process responsible for the acute episodes of pain (characteristic of the sickle cell diseases) is often involved in the acute chest structure. Inflammation associated with the infarct then causes splinting, hypoventilation, and hypoxia and further vaso-occlusion. The relationship with adult respiratory distress syndrome and fat embolism is also discussed. Use of the incentive spirometer combined with effective analgesia when chest pain is present is advocated for prevention of the pulmonary infiltrates. Newer understanding of the role of nitric oxide in regulating oxygen transport and its relationship to blood transfusions used in therapy of the acute chest syndrome are discussed. | Bone involvement is the commonest clinical manifestation of sickle cell disease both in the acute setting such as painful vaso-occlusive crises, and as a source of chronic, progressive disability such as avascular necrosis. Management of these problems is often difficult because of the diagnostic imprecision of most laboratory and imaging investigations and because of the lack of evidence for most surgical procedures in sickle cell disease. This review first discusses the acute problems related to bone involvement in sickle cell disease, with particular reference to differentiating infection from infarction, and then describes the long-term effects of sickle cell disease on bone mineral density, growth, and chronic bone and joint damage. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,668 |
Obstetric patients diagnosed with abnormal placentation (placenta accreta, increta or percreta) are at increased risk of major postpartum hemorrhage and cesarean hysterectomy. Obstetric anesthesiologists are primarily involved in intraoperative transfusion management in these cases. Hemoglobin assessment is invaluable for assisting transfusion decision-making during the acute period of obstetric hemorrhage. However, laboratory and point-of-care tests of hemoglobin concentration are time-dependent and intermittent, and do not provide a real-time assessment of change during the acute phase of blood loss. A new non-invasive hemoglobin monitor has been introduced recently, which provides real-time measurement of hemoglobin values (SpHb) using multi-wavelength pulse co-oximetry. We present a review of five patients with suspected abnormal placentation who received SpHb monitoring during cesarean hysterectomy at our institution. We discuss the potential clinical utility of non-invasive hemoglobin monitoring for pregnant patients at high risk of obstetric hemorrhage, and the potential role of SpHb in guiding transfusion therapy. | Noninvasive hemoglobin (Hb) monitoring devices are available in the clinical setting, but their accuracy and precision against central laboratory Hb measurements have not been evaluated in a systematic review and meta-analysis. ::: We conducted a comprehensive search of the literature (2005 to August 2013) with PubMed, Web of Science and the Cochrane Library, reviewed references of retrieved articles, and contacted manufactures to identify studies assessing the accuracy of noninvasive Hb monitoring against central laboratory Hb measurements. Two independent reviewers assessed the quality of studies using recommendations for reporting guidelines and quality criteria for method comparison studies. Pooled mean difference and standard deviation (SD) (95% limits of agreement) across studies were calculated using the random-effects model. Heterogeneity was assessed using the I2 statistic. ::: A total of 32 studies (4425 subjects, median sample size of 44, ranged from 10 to 569 patients per study) were included in this meta-analysis. The overall pooled random-effects mean difference (noninvasive—central laboratory) and SD were 0.10 ± 1.37 g/dL (−2.59 to 2.80 g/dL, I2 = 95.9% for mean difference and 95.0% for SD). In subgroup analysis, pooled mean difference and SD were 0.39 ± 1.32 g/dL (−2.21 to 2.98 g/dL, I2 = 93.0%, 71.4%) in 13 studies conducted in the perioperative setting and were −0.51 ± 1.59 g/dL (−3.63 to 2.62 g/dL, I2 = 83.7%, 96.4%) in 5 studies performed in the intensive care unit setting. ::: Although the mean difference between noninvasive Hb and central laboratory measurements was small, the wide limits of agreement mean clinicians should be cautious when making clinical decisions based on these devices. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,669 |
AIM ::: To determine the role of endothelium-derived contracting factor (EDCF) in the response to endothelin-1 in arteries with regenerated endothelium. ::: ::: ::: METHODS ::: Rings of porcine coronary arteries, with and without endothelium of previously deendothelialized left anterior descending coronary arteries and native left circumflex coronary arteries, were suspended in conventional organ chambers for the measurement of isometric force. ::: ::: ::: RESULTS ::: In quiescent rings of the previously deendothelialized left anterior descending coronary artery treated with the NO-synthase inhibitor nitro-L-arginine, endothelin-1 caused contractions which were larger in rings with than that in those without endothelium. Under the same experimental conditions, in the left circumflex coronary artery, the contractions to endothelin-1 were augmented markedly by the removal of the endothelium. In rings with endothelium of the previously deendothelialized left anterior descending coronary artery, indometacin (inhibitor of cyclooxygenase) and ridogrel (thromboxane A2 receptor antagonist and inhibitor of thromboxane synthase) inhibited contractions to endothelin-1. Dazoxiben (inhibitor of thromboxane synthase) inhibited, to the same extent as indometacin and ridogel, the response to higher concentrations of endothelin-1. The endothelium-dependent component of the response to lower concentrations of endothelin-1 was inhibited by indometacin and ridogrel, but not by dazoxiben. In rings without endothelium of both previously deendothelialized left anterior descending and native left circumflex coronary arteries, indometacin and ridogrel did not affect the contractions to endothelin-1. ::: ::: ::: CONCLUSION ::: These findings suggest that in regenerated endothelium, high concentrations of endothelin-1 stimulate the release of thromboxane A2. Endoperoxides generated by activation of endothelial cyclooxygenase may be the endothelium-derived contracting factor(s) released in regenerated endothelium by lower concentrations of the peptide. | Endothelial dysfunction is a common feature of hypertension, and it results from the imbalanced release of endothelium-derived relaxing factors (EDRFs; in particular, nitric oxide) and endothelium-derived contracting factors (EDCFs; angiotensin II, endothelins, uridine adenosine tetraphosphate, and cyclooxygenase-derived EDCFs). Thus, drugs that increase EDRFs (using direct nitric oxide releasing compounds, tetrahydrobiopterin, or L-arginine supplementation) or decrease EDCF release or actions (using cyclooxygenase inhibitor or thromboxane A2/prostanoid receptor antagonists) would prevent the dysfunction. Many conventional antihypertensive drugs, including angiotensin-converting enzyme inhibitors, calcium channel blockers, and third-generation beta-blockers, possess the ability to reverse endothelial dysfunction. Their use is attractive, as they can address arterial blood pressure and vascular tone simultaneously. The severity of endothelial dysfunction correlates with the development of coronary artery disease and predicts future cardiovascular events. Thus, endothelial dysfunction needs to be considered as a strategic target in the treatment of hypertension. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,670 |
Objective: To examine the usefulness of ratio of maximal swelling to normal cross sectional area (CSA) of median nerve with ultrasound in patients with carpal tunnel syndrome (CTS) and healthy controls. Method: Patients with electrodiagnostically proven CTS underwent ultrasonography of the median nerve. The median nerve area was measured at three points (maximal swelling site, 2 cm proximal to maximal swelling site, 12 cm proximal to maximal swelling site) and compared to values from asymptomatic volunteers. Results: The ratio of maximal swelling site to 12 cm proximal was 1.340.14 in asymptomatic volunteers and 2.310.43 in patients presenting with CTS. The ratio of maximal swelling site to 12 cm proximal gave 73.7% sensitivity and 90.0% specificity. While using only median nerve area at the wrist resulted in 81.6% sensitivity and 70.0% specificity, depending on the cutoff value used. Conclusion: The ratio of maximal swelling site to proximal in patients with CTS is elevated as compared to asymptomatic controls. The ratio of maximal swelling site to 12 cm proximal has higher specificity to diagnose CTS, and may be superior to measuring median nerve area at the wrist alone. | Objective ::: To verify the feasibility of initial parameters of ultrasonography or electromyography for the prediction of effect after steroid injection therapy in a carpal tunnel syndrome (CTS) patient. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,671 |
Neurological dysfunction, seizures and brain atrophy occur in a broad spectrum of acute and chronic neurological diseases. In certain instances, over-stimulation of N-methyl-D-aspartate receptors has been implicated. Quinolinic acid (QUIN) is an endogenous N-methyl-D-aspartate receptor agonist synthesized from L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D-aspartate neuronal damage and dysfunction. Conversely, the related metabolite, kynurenic acid, is an antagonist of N-methyl-D-aspartate receptors and could modulate the neurotoxic effects of QUIN as well as disrupt excitatory amino acid neurotransmission. In the present study, markedly increased concentrations of QUIN were found in both lumbar cerebrospinal fluid (CSF) and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicaemia) independent of breakdown of the blood-brain barrier. The concentrations of kynurenic acid were also increased, but generally to a lesser degree than the increases in QUIN. In contrast, no increases in CSF QUIN were found in chronic neurodegenerative disorders, depression or myoclonic seizure disorders, while CSF kynurenic acid concentrations were significantly lower in Huntington's disease and Alzheimer's disease. In inflammatory disease patients, proportional increases in CSF L-kynurenine and reduced L-tryptophan accompanied the increases in CSF QUIN and kynurenic acid. These responses are consistent with induction of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway which converts L-tryptophan to kynurenic acid and QUIN. Indeed, increases in both indoleamine-2,3-dioxygenase activity and QUIN concentrations were observed in the cerebral cortex of macaques infected with retrovirus, particularly those with local inflammatory lesions. Correlations between CSF QUIN, kynurenic acid and L-kynurenine with markers of immune stimulation (neopterin, white blood cell counts and IgG levels) indicate a relationship between accelerated kynurenine pathway metabolism and the degree of intracerebral immune stimulation. We conclude that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease. In conjunction with our previous reports that CSF QUIN concentrations are correlated to objective measures of neuropsychological deficits in HIV-1-infected patients, we hypothesize that QUIN and kynurenic acid are mediators of neuronal dysfunction and nerve cell death in inflammatory diseases. Therefore, strategies to attenuate the neurological effects of kynurenine pathway metabolites or attenuate the rate of their synthesis offer new approaches to therapy. | Background: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD. Methods: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46.5%) of these patients were diagnosed with childhood autism, 16 (24.6%) with Asperger syndrome, 12 (18.5%) with atypical autism, 1 (1.5%) with Rett syndrome, and 6 (9.2%) with other ASD. The serum levels of the following markers were measured in the children with ASD and compared to those in 30 healthy children: TRP, KYN, kynurenic acid (KA), 3-hydroxykynurenine, and quinolinic acid. Results: The mean serum level of KA was significantly lower in the ASD group than in the healthy controls (28.97 vs. 34.44 nM, p = 0.040), while the KYN/KA ratio was significantly higher in the ASD group (61.12 vs. 50.39, p = 0.006). The same relative values were found when comparing the childhood autism subgroup with the controls. Also, the mean serum level of TRP was significantly lower in children with a subdiagnosis of childhood autism than in those with Asperger syndrome (67.26 vs. 77.79 μM, p = 0.020). Conclusion: Our study indicates that there is an increased neurotoxic potential and also a possible lower KYN aminotransferase activity in ASD. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,672 |
BACKGROUND-These studies were initiated to confirm that high-level thrombomodulin overexpression is sufficient to limit neointima formation after mechanical overdilation injury. METHODS AND RESULTS-An adenoviral construct expressing thrombomodulin (Adv/RSV-THM) was created and functionally characterized in vitro and in vivo. The impact of local overexpression of thrombomodulin on neointima formation 28 days after mechanical overdilation injury was evaluated. New Zealand White rabbit common femoral arteries were treated with buffer, viral control, or Adv/RSV-THM and subjected to mechanical overdilation injury. The treated vessels (n=4 per treatment) were harvested after 28 days and evaluated to determine intima-to-media (I/M) ratios. Additional experiments were performed to determine early (7-day) changes in extracellular elastin and collagen content; local macrophage, T-cell, and neutrophil infiltration; and local thrombus formation as potential contributors to the observed impact on 28-day neointima formation. The construct significantly decreased neointima formation after mechanical dilation injury in this model. By histological analysis, buffer controls exhibited mean I/M ratios of 0.76+/-0.06%, whereas viral controls reached 0.77+/-0.08%; in contrast, Adv/RSV-THM reduced I/M ratios to 0.47+/-0.06%. Local inflammatory infiltrate decreased in the Adv/RSV-THM group relative to controls, whereas matrix remained relatively preserved. Rates of early thrombus formation also decreased in Adv/RSV-THM animals. CONCLUSIONS-This construct thus offers a viable technique for promoting a locally neointima-resistant small-caliber artery via decreased thrombus bulk, normal matrix preservation, and decreased local inflammation without the inflammatory damage that has limited many other adenoviral applications. | Apolipoprotein A1 mimetic peptide (D-4F), synthesized from D-amino acid, enhances the ability of high-density lipoprotein to protect low-density lipoprotein (LDL) against oxidation in atherosclerotic disease. Using a rat model of type I diabetes, we investigated whether chronic use of D-4F would lead to up-regulation of heme oxygenase (HO)-1, endothelial cell marker (CD31 + ), and thrombomodulin (TM) expression and increase the number of endothelial progenitor cells (EPCs). Sprague-Dawley rats were rendered diabetic with streptozotocin (STZ) and either D-4F or vehicle was administered, by i.p. injection, daily for 6 weeks (100 μg/100 g b.wt.). HO activity was measured in liver, kidney, heart, and aorta. After 6 weeks of D-4F treatment, HO activity significantly increased in the heart and aorta by 29 and 31% ( p p + expression. D-4F administration increased antioxidant capacity, as reflected by the decrease in oxidized protein and oxidized LDL, and enhanced EPC function and/or repair, as evidenced by the increase in EPC endothelial nitric-oxide synthase (eNOS) and prevention of vascular TM and CD31 + loss. In conclusion, HO-1 and eNOS are relevant targets for D-4F and may contribute to the D-4F-mediated increase in TM and CD31 + , the antioxidant and anti-inflammatory properties, and confers robust vascular protection in this animal model of type 1 diabetes. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,673 |
INTRODUCTION ::: Altitude decompression sickness (DCS) that involves the central nervous system (CNS) is a rare but potentially serious condition. Identification of early symptoms and signs of this condition might improve treatment. ::: ::: ::: METHODS ::: We studied data from 26 protocols carried out in our laboratory over the period 1983-2003; all were designed to provoke DCS in a substantial proportion of subjects. The data set included 2843 cases. We classified subject-exposures that resulted in DCS as: 1) neurological DCS of peripheral and/or central origin (NEURO); 2) a subset of those that involved only the CNS (CNS); and 3) all other cases, i.e., DCS cases that did not have a neurological component (OTHER). For each case, echo imaging data were used to document whether venous gas emboli (VGE) were present, and their level was classified as: 1) any level, i.e., Grade 1 or higher (VGE-1); and 2) high level, Grade 4 (VGE-4). ::: ::: ::: RESULTS ::: There were 1108 cases of altitude DCS in the database; 218 were classified as NEURO and 49 of those as CNS. VGE-1 were recorded in 83.8% of OTHER compared with 58.7% of NEURO and 55.1% of CNS (both p < 0.001 compared with OTHER). The corresponding values for VGE-4 were 48.8%, 37.0%, and 34.7% (p < 0.001, compared to OTHER). Hyperbaric oxygen (HBO) was used to treat about half of the CNS cases, while all other cases were treated with 2 h breathing 100% oxygen at ground level. ::: ::: ::: DISCUSSION ::: Since only about half of the rare cases of hypobaric CNS DCS cases were accompanied by any level of VGE, echo imaging for bubbles may have limited application for use as a predictor of such cases. | Objective:To demonstrate that U-2 pilot occupational exposure to hypobaria leads to increased incidence of white matter hyperintensities (WMH) with a more uniform distribution throughout the brain irrespective of clinical neurologic decompression sickness history. Methods:We evaluated imaging findings in 102 U-2 pilots and 91 controls matched for age, health, and education levels. Three-dimensional, T2-weighted, high-resolution (1-mm isotropic) imaging data were collected using fluid-attenuated inversion recovery sequence on a 3-tesla MRI scanner. Whole-brain and regional WMH volume and number were compared between groups using a 2-tailed Wilcoxon rank sum test. Results:U-2 pilots demonstrated an increase in volume (394%; p = 0.004) and number (295%; p < 0.001) of WMH. Analysis of regional distribution demonstrated WMH more uniformly distributed throughout the brain in U-2 pilots compared with mainly frontal distribution in controls. Conclusion:Pilots with occupational exposure to hypobaria showed a significant increase in WMH lesion volume and number. Unlike the healthy controls with predominantly WMH in the frontal white matter, WMH in pilots were more uniformly distributed throughout the brain. This is consistent with our hypothesized pattern of damage produced by interaction between microemboli and cerebral tissue, leading to thrombosis, coagulation, inflammation, and/or activation of innate immune response, although further studies will be necessary to clarify the pathologic mechanisms responsible. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,674 |
Background: Many previous studies have discussed hand and foot reflexology which is useful for reducing postpartum pain. However, previous studies presented different results related to foot massage, time and pain changes, so that in this systematic review aimed at supporting non-pharmacological nursing interventions of the hands and feet reflexology associated with postpartum enhancement by looking at these three types namely : duration of massage, time of massage and changes in pain. Objective : This study aims to analyze the duration, time, and results of hand or foot reflexology in reducing maternal postpartum pain. Methods: A systematic review through maternity nursing articles to analyze the effects of hand or foot reflexology in reducing postpartum pain. Search articles using electronic databases namely Sciene Direct, Pubmed, PMC, Google Schoolar and Scopus. Articles that meet the inclusion criteria will be collected and analyzed systematically. Results: In a systematic review it is explained that hand or foot reflexology can reduce postpartum maternal pain but in the duration and timing of the intervention still need consideration from further researchers. Conclusion: Based on the results of the study, hand or foot reflexology is recommended to reduce pain, specifically postpartum pain | INTRODUCTION ::: Ice pack is effective for alleviating postpartum perineal pain in primiparous women while multiparous women's levels of perineal pain appear to be poorly explored. Ice pack is a low-cost non-invasive localised treatment that can be used with no impact on breastfeeding. However, how long perineal analgesia persists after applying an ice pack is still unknown. ::: ::: ::: OBJECTIVE ::: To evaluate if perineal analgesia is maintained up to 2h after applying an ice pack to the perineum for 20min. ::: ::: ::: METHOD ::: A quasi-experimental study, using a pre and post-test design, was undertaken with a sample size of 50 multiparous women in Brazil. Data was collected by structured interview. The intervention involved a single application of an ice pack applied for 20min to the perineal area of women who reported perineal pain ≥3 by use of a numeric rating scale (0-10), with intact perineum, 1st or 2nd degree lacerations or episiotomy, between 6 and 24h after spontaneous vaginal birth. Perineal pain was evaluated at three points of time: before, immediately after and 2h after applying an ice pack. ::: ::: ::: RESULTS ::: Immediately after applying an ice pack to the perineal area, there was a significant reduction in the severity of perineal pain reported (5.4 vs. 1.0, p<0.0005), which continued for 1h 35min up to 2h after the local application. ::: ::: ::: CONCLUSION ::: Ice pack application for 20min is effective for alleviating postpartum perineal pain and continues to be effective between 1h 35min for up to 2h. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,675 |
INTRODUCTION ::: Hidradenitis suppurativa is a chronic inflammatory disease characterized by significant morbidity. Current medical therapies are usually only minimally effective. ::: ::: ::: OBJECTIVE ::: To assess the efficacy and safety of infliximab monotherapy for the treatment of severe extensive refractory forms of hidradenitis suppurativa. ::: ::: ::: DESIGN ::: A retrospective study in a group of 6 patients who received treatment with infliximab for hidradenitis suppurativa, in the Dermatology Department of the University Hospital of Puerto Real in the last year. The dose was 5-10 mg/kg at weeks 0, 2 and 6, followed by a maintenance dose every 4 weeks. Subjective and objective efficacy was assessed before and after each treatment session. ::: ::: ::: RESULTS ::: All patients experienced improvement in subjective symptoms after the initial dose. A decrease in exudation, the size and number of lesions and less development of fistulous tracts were observed. The patients were followed up during 6 months. Treatment was generally well tolerated and there was only one mild reaction to the infusion in the form of headache. No patient required treatment discontinuation due to adverse effects. ::: ::: ::: CONCLUSIONS ::: Infliximab was shown to be an effective therapeutic alternative for severe extensive forms of hidradenitis suppurativa when it is used as monotherapy. | OBJECTIVES ::: To conduct a systematic review of the effectiveness of various modalities to treat hidradenitis suppurativa (HS) and to establish recommendations on its appropriate management. ::: ::: ::: DATA SOURCES ::: MEDLINE, Cochrane, and PubMed databases. ::: ::: ::: STUDY SELECTION ::: English-language prospective, retrospective, and case studies describing at least 4 patients with HS. ::: ::: ::: DATA EXTRACTION ::: Data quality and validity were addressed by multiple reviewers using independent extraction. ::: ::: ::: DATA SYNTHESIS ::: Studies were categorized as treatments using antibiotics, biological agents, laser surgery, excisional surgery, or miscellaneous modalities. Of 62 publications included in the review, 4 studies met criteria to be assigned the highest grade for quality of evidence. ::: ::: ::: CONCLUSIONS ::: Shown to be effective treatments for HS were a clindamycin-rifampin combination regimen, a course of infliximab, monthly Nd:YAG laser sessions, and surgical excision and primary closure with a gentamicin sulfate-collagen sponge. Most therapies used to treat HS were supported by limited or weak scientific evidence. A treatment approach is presented based on the evidence and on clinical experience at the Follicular Disorders Clinic, Department of Dermatology, Henry Ford Hospital, Detroit, Michigan. This review emphasizes the need for large randomized controlled trials to evaluate treatment options for HS. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,676 |
A case history of a complication that occurred due to insertion of an oro gastric tube through a LMA supreme for a laparoscopic cholecystectomy is described. | PURPOSE ::: To compare LMA-ProSeal (LMA-PS) with endotracheal tube (ETT) with respect to pulmonary ventilation and gastric distension during laparoscopic cholecystectomy. ::: ::: ::: METHODS ::: We randomized 109 ASA I-III adults to LMA-PS or ETT after stratifying them as non-obese or obese (body mass index > 30 kg x m-2). After preoxygenation, anesthesia was induced with propofol, fentanyl and rocuronium. An LMA-PS (women #4, men #5) or ETT (women 7 mm, men 8 mm) was inserted and the cuff inflated. A #14 gastric tube was passed into the stomach in every patient and connected to continuous suction. Anesthesia was maintained with nitrous oxide, oxygen and isoflurane. Ventilation was set at 10 mL x kg-1 and 10 breaths x min-1. The surgeon, blinded to the airway device, scored stomach size on an ordinal scale of 0-10 at insertion of the laparoscope and upon decompression of the pneumoperitoneum. ::: ::: ::: RESULTS ::: There were no statistically significant differences in SpO2 or P(ET)CO2 between the two groups before or during peritoneal insufflation in either non-obese or obese patients. Median (range) airway pressure at which oropharyngeal leak occurred during a leak test with LMA-PS was 34 (18-45) cm water. Change in gastric distension during surgery was similar in both groups. Four of 16 obese LMA-PS patients crossed over to ETT because of respiratory obstruction or airway leak. ::: ::: ::: CONCLUSIONS ::: A correctly seated LMA-PS or ETT provided equally effective pulmonary ventilation without clinically significant gastric distension in all non-obese patients. Further studies are required to determine the acceptability of the LMA-PS for laparoscopic cholecystectomy in obese patients. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,677 |
OBJECTIVE ::: The aim of the present study is to evaluate the effect of ginger herbal spray on reducing dry mouth in patients with Type II diabetes. ::: ::: ::: MATERIALS AND METHODS ::: This clinical trial was conducted on 20 patients with Type II diabetes suffering from dry mouth. The control individual for each patient was the same patient himself/herself. Each patient filled out his/her questionnaire at three different times, (before treatment, after treatment with placebo, and after taking the drug). Furthermore, the Schirmer test was performed to measure the flow of saliva in the patients. The drug and the placebo were prepared as oral sprays containing herbal extracts of ginger. ::: ::: ::: RESULTS ::: The mean amount of saliva after using the ginger plant spray increased significantly (p<0.001). The mean amount of saliva after treatment with medication was considerably different from the mean amount of saliva after treatment with the placebo (p<0.001). Our study included patients aged between 49 and 69 years old, (mean age 58.6 years old, and the standard deviation 5.3). The minimum and the maximum periods of type II diabetes were 2 and 21 years, the mean and the standard deviation of which were 8.8 and 5.8, respectively. ::: ::: ::: CONCLUSION ::: With regard to the effectiveness of ginger herbal spray in rapidly increasing the patients' saliva and satisfaction as well as the acceptability of this type of medicine to treat dry mouths, ginger herbal spray could act as a new, cheap, and available treatment for diabetic patients with dry mouth. | Objectives: Treatment of dry mouth is the most common clinical challenge in the dental field. Although some remedies have been used to improve the signs and symptoms of xerostomia, none of them are absolutely satisfactory for the patients who have this alteration. In the current years, non-pharmacological treatments based on neuro-electro-stimulation for the treatment of xerostomia were developed. This review aimed at presenting recent developments for the treatment of xerostomia, applying neuro-electro-stimulation by miniaturized intraoral electrostimulators. Materials and Methods: A thorough literature search between 1986 and 2018 was carried out using PubMed Central, Scopus, National Science Library, ProQuest, and Google Scholar databases; the results were reviewed, prioritized, and the findings were compiled. Twenty-two studies were evaluated for the review. Results: This tool increases salivary secretion and improves xerostomia symptoms. Scientific trials have been carried out, which have revealed the wetting effect of the method described in this text. Conclusion: Neuro-electro-stimulation of the salivary gland plays an important role in the stimulation of saliva in patients who need further therapy and have poor quality of life. Intraoral electrostimulator offers a new non-pharmacological method for treating dry mouth. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,678 |
A model of myocardial oxygenation was developed that allows calculation of Po2 histograms under varying conditions. The model consists of parallel tissue cylinders with varying radii, simulating the heterogeneity of capillary spacing, in agreement with our previous experimental results. The facilitated diffusion of O2 by myoglobin, an additional resistance to diffusion at the capillary level, and the Michaelis-Menten type of O2 consumption were also incorporated. The shape of the histograms depends on input data. When no additional barrier to O2 transport is included, the histograms resemble those obtained with Po2 surface electrodes, and they are strongly dependent on heterogeneity in capillary spacing and capillary blood flow. On the other hand, an inclusion of an additional capillary barrier combined with the Michaelis-Menten type of O2 consumption can generate Po2 histograms similar to those derived from myoglobin cryospectroscopy. In this case, the Po2 histograms are relatively independent of heterogeneity of capillary spacing and blood flow. The facilitation of O2 diffusion by myoglobin has only a modest effect on the form of the histograms in all situations considered. | The aim of this study was to describe quantitatively changes in the coronary capillary network resulting from hypertrophy in spontaneously hypertensive rats (SHR) and a potential effect of long-term treatment of these animals with nifedipine. Age-matched male SHR and Wistar-Kyoto (WKY) rats were treated for 27 weeks. Four experimental groups were analyzed: (1) untreated SHR, (2) nifedipine-treated SHR, (3) untreated control WKY rats, and (4) nifedipine-treated WKY rats. Treatment significantly decreased systolic blood pressure in SHR, although normotensive pressures were not reached. SHR had significantly higher cardiac weight, which decreased in nifedipine-treated rats, but values remained above those in control animals. Morphometric evaluation revealed lower capillary density and larger capillary domain area in hearts from SHR, which were partially attenuated by treatment with nifedipine. Capillary domain area was also significantly larger at arteriolar portions compared with domains supplied at venular portions. Capillary segment length was consistently shorter on the venular than arteriolar portion of the capillary, whereas no differences were observed between hearts from WKY rats and SHR. Treatment with nifedipine resulted in a prolongation of segment length. Reconstruction of the three-dimensional capillary supply unit (capillary domain area times capillary segment length) revealed significant differences between the amount of tissue supplied by a capillary at its arteriolar portion than more distally, which was detectable in all experimental groups. In hypertrophic hearts from SHR this tissue volume is increased mainly because of longer intercapillary distances and larger domains, especially on arteriolar portions.(ABSTRACT TRUNCATED AT 250 WORDS) | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,679 |
OBJECTIVES ::: Nitric oxide reduces platelet adhesion and platelet-thrombus formation following angioplasty and inhibits smooth muscle cell (SMC) proliferation in vitro. In this study we investigated the effects of the nitric oxide donor molsidomine on SMC proliferation and intimal growth following experimental angioplasty. ::: ::: ::: METHODS ::: Bilateral carotid angioplasty was performed in 24 anesthetized pigs. Animals were randomized to receive oral molsidomine (whose active metabolite is SIN-1; 0.3 mg/kg every 8 h; n = 12) or placebo (n = 12) for 48 h before angioplasty and until the arteries were removed either 7 or 21 days (n = 12 each group) later. SMC proliferation was quantified by immunocytochemical staining with an antibody to the proliferating cell nuclear antigen (PCNA) and morphometric changes by computerized planimetry. SMC's were identified by alpha-actin staining. ::: ::: ::: RESULTS ::: After 3 weeks treatment with molsidomine there was a significant prolongation in bleeding time [mean +/- SEM] (151 +/- 6 to 187 +/- 7 s. P < 0.01) and a sustained increase in arterial wall cyclic GMP (6.57 +/- 1.29 to 13.24 +/- 1.02 pmol/mg protein, P < 0.05). Molsidomine significantly reduced intimal proliferation when compared with placebo in arteries with an intact internal elastic lamina at 7 days (4.3 +/- 0.7 vs. 9.6 +/- 1.9 PCNA index, P < 0.005) and medial proliferation at 7 days (2.4 +/- 0.2 vs. 4.2 +/- 0.7 PCNA index, P < 0.05) and at 21 days (1.3 +/- 0.1 vs. 1.9 +/- 0.2 PCNA index, P < 0.05) after angioplasty. In arteries with rupture of the internal elastic lamina, intimal and medial SMC proliferation were similar in molsidomine- and placebo-treated animals. Intimal cell number and intimal area were uninfluenced by treatment with molsidomine in either the presence or absence of rupture of the internal elastic lamina. ::: ::: ::: CONCLUSIONS ::: These results show for the first time that exogenous nitric oxide inhibits SMC proliferation following balloon angioplasty in vivo. The antiproliferative effects of nitric oxide are overwhelmed when injury is severe and are not associated with a reduction in intimal thickening. The inhibitory effects of nitric oxide on platelet adhesion and SMC proliferation identify a possible role for high local concentrations of nitric oxide to modify the vascular response to balloon angioplasty. | BACKGROUND ::: Stent luminal surface characteristics influence surface endothelialization. We hypothesize that luminal stent microgrooves created in the direction of coronary flow accelerate endothelial cell migration, resulting in lower levels of neointimal formation. ::: ::: ::: METHODS AND RESULTS ::: Surface coverage efficiency was evaluated in vitro by allowing human aortic endothelial cells (HAEC) to migrate onto microgrooved (G) or smooth (NG) surfaces. HAEC functionality was assessed by proliferation rate, apoptosis rate, nitric oxide production, and inflammatory markers TNF-α and VCAM-1 expression. Early endothelialization and restenosis studies were performed using the porcine coronary injury model. Stainless steel stents of identical design with (GS) and without (NGS) luminal microgrooves were used. The commercially available Multi-Link Vision (MLVS) stent of identical design was used as a control. The degree of GS and NGS surface endothelialization was compared at 3 days. Biocompatibility and tissue response outcomes were evaluated at 28 days. The in vitro study demonstrated that at 7 days the presence of surface microgrooves increased HAEC migration distance >2-fold. Cell proliferation rate and nitric oxide production were increased and apoptosis rate was decreased. There was no difference in inflammatory marker expression. At 3 days, coronary artery stent endothelialization was significantly increased in GS compared with NGS (81.3% versus 67.5%, P=0.0002). At 28 days, GS exhibited lower neointimal thickness compared with either NGS (21.1%, P=0.011) or MLVS (40.8%, P=0.014). ::: ::: ::: CONCLUSION ::: Parallel microgrooves on coronary stent luminal surfaces promote endothelial cell migration and positively influence endothelial cell function, resulting in decreased neointimal formation in the porcine coronary injury model. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,680 |
An important feature of asthma is airway hyperresponsiveness in which the airway smooth muscle (ASM) is fundamentally involved. How asthmatic ASM differs from healthy is a current focus for research. We have shown previously that WNT-5A is increased in asthmatic ASM. Here, we tested the hypothesis that WNT-5A is a determinant of the contractile response of ASM. Using bovine smooth muscle strips, we found that pre-incubation with WNT-5A increased maximum tension by histamine. We used human ASM cells to study the underlying mechanisms. In ASM loaded with the calcium dye Fura-2, neither direct exposure to WNT-5A nor pre-incubation had any effect on calcium handling. Moreover, WNT-5A treatment did not significantly change IP3R, SERCA2 and RyR expression. Next, we found that exposure to WNT-5A increased abundance of filamentous actin, without affecting the total actin pool. These changes could be completely prevented by treatment with a Rho kinase inhibitor. Interestingly, ASM cells that adopted a contractile phenotype also showed greater WNT-5A protein expression compared to the proliferative phenotype. We next assessed whether TGF-β1 played an upstream role in the WNT-5A response. We found that WNT-5A siRNA not only blocked TGF-β1-induced actin polymerization, but could also abrogate TGF-β1-induced accumulation of α-SMA. In line with this contention, adding WNT-5A on top of TGF-β1 synergistically induced α-SMA abundance. In summary, WNT-5A promotes agonist-induced airway smooth muscle contraction, most likely by increasing actin polymerization and actin expression in concerted action with TGF-β1. These results may be relevant in the understanding of AHR and warrant further investigation. | Chronic lung diseases represent a major public health problem with only limited therapeutic options. An important unmet need is to identify compounds and drugs that target key molecular pathways involved in the pathogenesis of chronic lung diseases. Over the last decade, there has been extensive interest in investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal alterations have been linked to pulmonary disease pathogenesis and progression. Here, we comprehensively review the cumulative evidence for WNT pathway alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis, pulmonary arterial hypertension, asthma and COPD. While many studies have focused on the canonical WNT/β-catenin signalling pathway, recent reports highlight that non-canonical WNT signalling may also significantly contribute to chronic lung pathologies; these studies will be particularly featured in this review. We further discuss recent advances uncovering the role of WNT signalling early in life, the potential of pharmaceutically modulating WNT signalling pathways and highlight (pre)clinical studies describing promising new therapies for chronic lung diseases. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,681 |
2. King AB, Clark D, Wolfe GS. The number of basal rates required to achieve near-normal basal glucose control in pump-treated type 2 diabetes. Diab Technol Therap. 2012;14:900-903. 3. Riddle MC, Rosenstock J, Gerich J, Insulin Glargine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26:3080-3086. | Suboptimal drug adherence represents a major challenge to effective primary and secondary prevention of cardiovascular disease. While adherence is influenced by multiple considerations, polypharmacy and dosing frequency appear to be rate-limiting factors in patient satisfaction and subsequent adherence. The cardiovascular and metabolic therapeutic areas have recently benefited from a number of advances in drug therapy, in particular protease proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and incretin-based therapies, respectively. These drugs are administered subcutaneously and offer efficacious treatment options with reduced dosing frequency. Whilst patients with diabetes and diabetologists are well initiated to injectable therapies, the cardiovascular therapeutic arena has traditionally been dominated by oral agents. It is therefore important to examine the practical aspects of treating patients with these new lipid-lowering agents, to ensure they are optimally deployed in everyday clinical practice. | We apply the method of Arzhantseva-Ol'shanskii to prove that for an exponentially generic (in the sense of Ol'shanskii) class of one-relator groups the isomorphism problem is solvable in at most exponential time. ::: This is obtained as a corollary of our more general result that for any fixed integers $m>1, n>0$ there is an exponentially generic class of $m$-generator $n$-relator groups where every group has only one Nielsen equivalence class of $m$-tuples generating non-free subgroups. This means that a group $G$ in this class has has only one non-free $m$-generated subgroup, namely $G$ itself. Hence for any homomorphism for an $m$-generated group to $G$ the image of this homomorphism is either free or is equal to $G$. Applied to injective homomorphisms from $G$ to itself this implies that $G$ is co-Hopfian. Moreover, every automorphism of $G$ is "freely induced", that is, it lifts to an automorphism of the free group $F_m$. ::: All of these results are obtained by folding methods without using the theory of JSJ-decomposition or the R-tree techniques deployed by Zlil Sela in his famous solution of the isomorphism problem for torsion-free word-hyperbolic groups. | eng_Latn | 22,682 |
BACKGROUND: Sinusoidal obstruction syndrome (SOS) occurs in patients undergoing hematopoietic cell transplantation and chemotherapy. The chemotherapeutic drugs oxaliplatin and cyclophosphamide cause SOS. Sesame oil is a nutrient-rich antioxidant popular in alternative medicine. It contains sesamin, sesamol, and sesamolin, all of which contribute to its antioxidant property. The authors investigated the protective effect of prophylactic sesame oil against monocrotaline-induced SOS in rats. METHODS: Male Sprague-Dawley rats were gavaged with a single dose of sesame oil (0.5, 1, 2, or 4 mL/kg). One hour later, those rats were gavaged with monocrotaline (90 mg/kg) to induce SOS. Control rats were treated with saline only. Aspartate transaminase, alanine transaminase, laminin, collagen, myeloperoxidase, nitrate content, lipid peroxidation, glutathione levels, matrix metalloproteinase (MMP)-9, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were assessed 48 hours after the monocrotaline gavage. RESULTS: All tested parameters except TIMP-1, laminin, collagen, and glutathione were higher in monocrotaline-treated rats than in saline-only-treated control rats. In sesame oil-treated rats, all tested parameters except TIMP-1, laminin, collagen, and glutathione were significantly attenuated compared with monocrotaline-only-treated rats. Sesame oil downregulated MMP-9 expression but upregulated TIMP-1 expression in monocrotaline-only-treated rats. In addition, a histological analysis of liver tissue samples showed that sesame oil showed significant protection. CONCLUSION: A single prophylactic dose of sesame oil protects against SOS by downregulating MMP-9 expression, upregulating TIMP-1 expression, and inhibiting oxidative stress. | Treatment of hematological malignancy with antibody-drug conjugates (ADCs) may cause liver injury. ADCs deliver a toxic moiety into antigen-expressing tumor cells, but may also injure hepatic sinusoids (sinusoidal obstruction syndrome; SOS). We studied patients who received an anti-CD22/calicheamicin conjugate (inotuzumab ozogamicin; InO) to gain insight into mechanisms of sinusoidal injury, given that there are no CD22+ cells in the normal liver, but nonspecific uptake of ADCs by liver sinusoidal endothelial cells (LSECs). Six hundred thirty-eight patients (307 with acute lymphocytic leukemia [ALL], 311 with non-Hodgkin's lymphoma [NHL]) were randomized to either InO or standard chemotherapy (controls). While blinded to treatment assignment, we reviewed all cases with hepatobiliary complications to adjudicate the causes. Frequency of SOS among patients who received InO was 5 of 328 (1.5%), compared to no cases among 310 control patients. Drug-induced liver injury (DILI) developed in 26 (7.9%) InO recipients and 3 (1%) controls. Intrahepatic cholestasis (IHC) was observed in 4.9% of InO recipients and in 5.5% of controls. Subsequent to the randomization study, 113 patients with ALL underwent allogeneic hematopoietic cell transplantation (HCT); frequency of SOS in those previously exposed to InO was 21 of 79 (27%) versus 3 of 34 (9%) in controls. An exploratory multivariate model identified a past history of liver disease and thrombocytopenia before conditioning therapy as dominant risk factors for SOS after transplant. Conclusion: Frequencies of SOS and DILI after inotuzumab ozogamicin treatment were 1.5% and 7.9%, respectively, compared to none and 1% among controls who received standard chemotherapy. These data suggest that ADCs that do not target antigens present in the normal liver have a relatively low frequency of SOS, but a relatively high frequency of DILI. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,683 |
Total contact casting has been successful in treating neuropathic foot ulcers, but little information is available abouttreating patients with diabetes mellitus for whom total contact casting treatment for forefoot ulceration fails. Equinus deformity of the ankle and limited joint motion in a neuropathic foot can lead to abnormal foot pressures, resulting in failure of total contact casting. This report describes the technique of tendo-Achilles lengthening in conjunction with total contact casting and reports the results achieved in a randomly selected group of diabetic patients with unhealed forefoot ulcerations. Surgical correction with percutaneous tendo-Achilles lengthening and total contact casting can result in rapid healing of the forefoot ulcer and helps prevent ulcer recurrence. | The International Working Group on the Diabetic Foot (IWGDF) has published evidence - based guideline s on the prevention and management of diabetic foot disease since 1999. This guideline is on the use of offloading interventions to promote healing foot ulcers in persons with diabetes and updates the previous IWGDF guideline . We followed the GRADE methodology to devise clinical questions and critically important outcomes in the PICO format , to conduct a systematic review of the medical - scientific literature , and to write recommendations and the irrationale. The recommendations are based on the quality of evidence found in the systematic review , expert opinion where evidence was not available, and a weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to the intervention. For healing a neuropathic plantar forefoot or midfoot ulcer in a person with diabetes, w e recommend that a non - removable knee - high offloading device is the first - choice of offloading treatment . A removable knee - high and removable ankle - high offloading device are to be considered as the second - and third - choice offloading treatment , respectively , if contraindications or patient intolerance to non - removable offloading exist . Appropriately fitting footwear combine d with felted foam can be considered as the fourth - choice offloading treatment. If non - surgical offloading fails, we recommend to consider surgical offloading interventions for healing metatarsal head and digital ulcers. We have added new recommendations for the use of offloading treatment for healing ulcers that are complicated with infection or ischemia, and for healing plantar heel ulcers. Offloading is arguably the most important of multiple interventions needed to heal a neuropathic plantar foot ulcer in a person with diabetes . Following these recommendations will help health care professionals and teams provide better care for diabetic patients who have a foot ulcer and are at risk for infection, hospitalisation and amputation. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,684 |
Summary Three cases of basal cell carcinoma (BCC) with extensive invasion are described. The first two patients had meningeal and cerebral involvement with exposure of their dural meninges following full thickness skull erosion. The third patient had bilateral orbital and optic nerve involvement resulting in complete blindness. All three patients subsequently died from their disease. | E-cadherin (E-CD) is a calcium-dependent cell-cell adhesion molecule which is expressed in almost all epithelial tissues. E-CD expression is involved in epidermal morphogenesis and is reduced during tumour progression of mouse epidermal carcinogenesis. It has been suggested that E-CD could play a role as an invasion-suppressor molecule. In the present work we have studied the E-CD expression in 31 patients with basal cell carcinoma (BCC) using an immunohistochemical technique with a monoclonal antibody (HECD-1) specific for human E-CD. E-CD expression was preserved in all specimens of superficial and nodular BCC, and was reduced in 10 of 15 infiltrative BCCs. A heterogeneous distribution of cells with different immunostaining intensity was more frequently observed in specimens of infiltrative BCC. These results suggest that E-CD might be related to the growth pattern and the local aggressive behaviour of BCC, and support the idea that E-CD might play a role as an invasion-suppressor molecule in vivo. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,685 |
In this randomized, double-blind, controlled study, we tested the hypothesis that the short-acting beta(1)-adrenoceptor antagonists esmolol and landiolol suppress hemodynamic changes and bispectral index (BIS) increases, both of which are induced by tracheal intubation under general anesthesia with sevoflurane alone. Forty-five patients were randomly assigned to the control, esmolol, and landiolol groups (n = 15 each). Anesthesia was induced with sevoflurane in oxygen, with an end-tidal concentration maintained at 1 minimum alveolar anesthetic concentration (MAC). Infusion of saline (control group), esmolol (bolus of 1 mg/kg and then 0.25 mg x kg(-1) x min(-1); esmolol group), or landiolol (bolus of 0.125 mg/kg and then 0.04 mg x kg(-1) x min(-1); landiolol group) was started 5 min after the induction of anesthesia and was continued throughout the study. Tracheal intubation was performed 12 min after anesthesia induction. There were no differences in overall changes of mean arterial blood pressure among the three groups, whereas, at 1-5 min after tracheal intubation, heart rate increased in all groups but was significantly slower in the esmolol and landiolol groups than in the control group (P < 0.05). BIS was between 96 and 98 for all patients at baseline and decreased during the induction of anesthesia. There were no differences in BIS among the three groups before laryngoscopy (39 +/- 5, 39 +/- 5, and 38 +/- 4 in the control, esmolol, and landiolol groups, respectively). BIS increased significantly in the control group (54 +/- 10; P < 0.05) 1 min after intubation, whereas it remained unchanged in the esmolol and landiolol groups (45 +/- 10 and 41 +/- 6, respectively). In conclusion, the increase in both heart rate and BIS after tracheal intubation under 1 MAC sevoflurane anesthesia was suppressed by the concomitant administration of either esmolol or landiolol. | The objective of this study was to examine the effects of low-dose infusion of landiolol on hemodynamics during tracheal intubation in elderly patients with cardiovascular disease. The study population consisted of 30 patients with American Society of Anesthesiologists physical status II and III, aged 65-77 years, who were scheduled to undergo elective surgery under general anesthesia. Patients were randomly divided into two groups (n = 15 each): a control group, receiving normal saline, and a landiolol group, receiving landiolol at 30 μg/kg/min. After oxygenation, 1 μg/kg of fentanyl was injected intravenously, followed by continuous infusion of normal saline or landiolol for 5 min. General anesthesia was induced and maintained with target-controlled infusion of propofol at a blood concentration of 4 μg/ml and tracheal intubation was performed 3 min after vecuronium injection. Heart rate, blood pressure, and bispectral index were measured before and after tracheal intubation. Results showed that low-dose continuous infusion of landiolol is an effective and relatively safe method of preventing an intubation-induced adrenergic response in elderly patients with cardiovascular disease. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,686 |
STUDY OBJECTIVE ::: This study aimed to evaluate the effects of zolpidem CR (controlled release) on sleep and nocturnal ventilation in patients with congestive heart failure, a population at risk for insomnia and poor sleep quality. ::: ::: ::: METHODS ::: Fifteen patients with heart failure (ischemic cardiomyopathy) and ejection fraction ≤ 45% in NYHA functional class I or II were evaluated with full polysomnography in a placebo-controlled, double-blind, randomized trial. Patients underwent three tests: (1) baseline polysomnography and, after randomization, (2) a new test with zolpidem CR 12.5 mg or placebo, and after 1 week, (3) a new polysomnography, crossing the "medication" used. ::: ::: ::: RESULTS ::: A 16% increase in total sleep time was found with the use of zolpidem CR and an increase in stage 3 NREM sleep (slow wave sleep). The apnea hypopnea index (AHI) did not change with zolpidem CR even after controlling for supine position; however, a slight but significant decrease was observed in lowest oxygen saturation compared with baseline and placebo conditions (83.60 ± 5.51; 84.43 ± 3.80; 80.71 ± 5.18, P = 0.002). ::: ::: ::: CONCLUSION ::: Zolpidem CR improved sleep structure in patients with heart failure, did not change apnea hypopnea index, but slightly decreased lowest oxygen saturation. | INTRODUCTION: Nonbenzodiazepine (non-BZD) sedative hypnotics (NBSH) refer to non-BZD sedatives that act as BZD receptor agonists such as zolpidem, zaleplon, and eszopiclone. Today, there is a high prevalence of insomnia with or without concurrent obstructive sleep apnea (OSA). Our goal was to study how NBSH use impacts the baseline apnea–hypopnea index (AHI) in patients with or without OSA. METHODS: PubMed/MEDLINE, Scopus, Web of Science and Cochrane Library databases were searched. RESULTS: Seventeen studies comprising a cumulative total of 2099 patients were identified in the last 30 years (between 1988 and 2017) that evaluated the effect of NBSH on respiratory parameters during sleep. The AHI mean (M) ± standard deviation (SD) in NBSH group was 13.17 ± 16.27 versus 15.94 ± 19.31 (mean difference [MD]-95% confidence interval [CI], 2.77 [1.463–4.076]). Six studies (100 patients) compared zolpidem with either placebo or no medication and demonstrated an AHI MD of −0.61 events/h (95% CI − 1.94, 0.71), overall effect Z = 0.9, P = 0.36. Four studies (362 patients) compared eszopiclone with placebo and demonstrated an AHI MD of −5.73 events/h0 (95% CI − 8.90, −0.2.57). Two large studies (979 patients) compared both zolpidem and eszopiclone to no medication and found AHI MD of −1.66 events/h (95% CI − 5.87, 0.2.55). CONCLUSIONS: The majority of patients using NBSH did not develop any worsening of existing AHI, when using NBSH, regardless of their baseline AHI values (mild, moderate, severe, or no OSA). On average, the AHI improved minimally with NBSH and eszopiclone showed the largest difference in AHI with an MD of −5.73 events/h. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,687 |
mg/d alendronate sodium with calcium salts for 1 year. The patient consulted 3 days after the presentation of extremely painful ulcers on the oral mucosa, palate, tongue, and lower lip. Following careful questioning, the patient reported having allowed the alendronate tablet to dissolve in his mouth on one occasion several days previously because he was traveling. The second case was a 57-year-old woman, postmenopausal for 10 years, who had received treatment for osteoporosis with alendronate 10 mg/d for 2 weeks prior to consultation. She presented painful ulcers on the tongue, palate, and oral mucosa that had been present for 2 days (Figures 1 and 2). On questioning she stated that she had experienced difficulty in swallowing a tablet that had dissolved in her mouth some days before the lesions appeared. Neither patient had a previous history of gastric problems, mouth ulcers, or herpes. Other mucosae were not affected and no related skin lesions were present in either case. Both patients had taken the drug (alendronate sodium) incorrectly and the erosions appeared shortly after the tablet had dissolved in the mouth. The lesions were diagnosed as oral ulcerations caused by alendronate sodium and treatment with the drug was suspended. The lesions were treated and healed completely within 2 weeks. Bisphosphonates are synthetic pyrophosphate analogs that bind to hydroxylapatite in bone inhibiting osteoclastic activity. Alendronate sodium is a primary aminobisphosphonate used in the treatment of postmenopausal osteoporosis (10 mg/d) and Paget disease (40 mg/d), which acts by inhibiting osteoclastic resorption. It has also been used in the treatment of bone metastasis and tumor-related hypercalcemia. Secondary skin conditions are rare, with reports of lichenoid eruptions, superficial erythema annulare,1 urticaria, angioedema, erythema multiforme, fixed pigmented erythema, eczema eruptions, and pruritus. Exceptional cases of mouth ulcers restricted to the oral mucosa have been reported before.2-4 Erosive esophagitis,5 esophageal ulcers, dysphagia, and retrosternal pain have been associated with the ingestion of alendronate sodium. As the drug is administered orally, the patient must be instructed well, and be provided with the following advice in order to allow adequate absorption and to reduce adverse effects to a minimum6: To the Editor: Alendronate sodium is a primary aminobisphosphonate, widely used in the treatment of postmenopausal osteoporosis and Paget disease. Most of the adverse effects reported involve the esophageal and gastric mucosa. Lesions in the oral mucosa are less well known, although some cases have been reported. We present 2 cases of ulceration of the oral mucosa caused by incorrect administration of alendronate sodium tablets. The first case involved a 68-year-old man, whose only relevant history was hypertension treated with verapamil for the last 3 years and collapsed vertebra treated with 10 Mouth Sores Caused by Alendronate | Corticosteroids are the principal cause of secondary osteoporosis due to drug treatment. Doses of more than 5 mg daily and periods of treatment lasting more than 3 months increase the risk of osteoporosis and fragility fractures. It is therefore essential to be aware of measures to reduce the risk of osteoporosis in our patients. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,688 |
Conventional treatment of non-small cell lung cancer (NSCLC) has apparently reached a plateau of effectiveness in improving the survival of the patients. For that reason the search for new therapeutic strategies in this type of tumor is justified. 1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific to P3 Ab1 MAb, which reacts with NeuGc-containing gangliosides, sulfatides and with antigens expressed in some tumors, including those from the lung. We report the treatment with aluminum hydroxide-precipitated 1E10 MAb of 34 stage IIIb and 37 stage IV NSCLC patients. These patients were treated with the anti-idiotype vaccine, after received standard chemotherapy and radiotherapy, in a compassionate-use basis study. Patients received five bi-weekly injections of 1 mg of 1E10/Alum, other 10 doses at 28-day intervals and later the patients who maintained a good performance status continued to be immunized at this same time interval. No evidence of unexpected or serious adverse effects was reported. The median survival time of the 56 patients who entered the study with partial response or disease stabilization and with a PS 1 after the first line of chemo/radiotherapy, was 11.50 months from starting vaccination. In contrast, the median survival time calculated for patients who started vaccination with progressive disease and/or a PS2 was 6.50 months. | P3 is a mouse monoclonal antibody (mAb) that binds to several NeuGc-containing gangliosides. It also reacts with antigens expressed in human breast tumors (Vázquez et al. (1995) Hybridoma , 14, 551-556). In this work, the binding specificity of P3 has been characterized in more detail using a panel of glycolipids that included several disialylated gangliosides and several chemical derivatives of NeuGc-GM3. The carboxyl group and the nitrogen function of sialic acid were found to play important roles in the antibody binding, whereas the glycerol tail appears to be nonrelevant. Molecular modeling was used to analyze the binding data, including the finding that P3 selectively recognizes the internal NeuGc in GD3. For this purpose, conformational studies of GD3 were performed using molecular dynamics. It was concluded that sialic acid binds the P3 antibody through its upper face (the one on which the carboxyl group is exposed) and the C4-C5 side of the sugar ring, whereas none or very little contact between the galactose residue and the protein is evident. Conformational analysis of GD3 revealed that, despite the large flexibility of the NeuGcalpha8NeuGc linkage, the P3 binding epitope on the external sialic acid is not well exposed for any of the possible conformations this linkage can adopt, whereas the internal sialic acid presents the epitope in a proper way for several of these conformations. As a final result, a coherent picture of the epitope that fits the wide binding data was obtained. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,689 |
Methods: We studied angiotensin-converting enzyme (ACE) gene polymorphism and lipid profiles in Kuwaiti children with uncomplicated type 1 diabetes. A total of 125 children with type 1 diabetes were matched in a case-control study on age and gender to 125 non-diabetic children as controls. Serum lipids (total cholesterol, TC; high-density lipoprotein cholesterol, HDL; low-density lipoprotein cholesterol, LDL-c; triglycerides, TG; apolipoprotein A1 and B, apo A1 and B; lipoprotein(a), Lp(a)); and glycated hemoglobin, HbA1c were evaluated according to ACE genotypes. ::: ::: Results: Genotype distributions were found to be similar in cases [ACE insertion/insertion (II) 9.6%, ACE insertion/deletion (ID) 38.4%, ACE deletion/deletion (DD) 52.0%], and controls (II 8.8%, ID 43.2%, DD 48.0%), and were characterized by higher frequencies of DD, ID, and lower frequencies of II. Diabetic children with DD genotype showed significantly higher levels of TC (p 30 mg/dL in children with a family history of CVD (p = 0.008). Lp(a) levels were correlated with HbA1c in the diabetic group (r = 0.239, p = 0.019), but when patients with poor glycemic control (HbA1c > 9%) were excluded, the significant correlation disappeared (r = 0.127, p = 0.381). After adjusting confounding between variables, the logistic regression analysis showed that the two significantly related variables with the rise in Lp(a) were increasing TC level and poor glycemic control. ::: ::: Conclusions: In children with type 1 diabetes, the role of ACE polymorphism as a probable contributor to CVD seems to be partially mediated through other factors such as poor glycemic control, TC, and Lp(a) level. A longitudinal study is recommended with a larger number of patients in each ACE genotype group in order to assess such associations. | A polymorphic AC repeat in intron 1 of the EGFR gene was genotyped on 352 healthy individuals and 118 women with breast cancer sampled from the Kuwaiti and Tunisian populations. We compared allele frequencies in these populations with published data on various ethnic groups. We found very close similarity between Tunisian and Kuwaiti populations for both allelic and genotypic frequencies and in both control and patient groups. Our analysis revealed clear interethnic differences between populations; in Europeans, allele 16 occurred predominantly, whereas in Tunisia and Kuwait allele 17 was the most frequent and allele 20 predominated in Asians. One hundred twenty-three healthy women, matched with the 118 breast cancer patients, were used as controls to test for associations between AC repeat and cancer risk. Strong evidence for such an association was found for allele 18 when considered alone (χ2=27.04, corrected p=0.0000016, OR=3.94) or with longer alleles (>17 repeats) (χ2=20.21, p=0.0005, OR=2.30). This contrasts with Asian populations where allele 16 was identified as the risk allele, showing allele heterogeneity depending on ethnicity. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,690 |
Increased adhesive forces between sickle erythrocytes and endothelial cells (EC) have been hypothesized to play a role in the initiation of vasoocclusion in sickle cell anemia. Erythrocyte/human umbilical vein EC interactions were studied under controlled flow conditions for normal (AA), homozygous sickle cell (SS), sickle cell trait (AS), mechanically injured normal, and "high-reticulocyte control" RBC by using video microscopy and digital image processing. The number of adherent RBC was determined at ten-minute intervals during a washout period. Results indicate that SS RBC were more adherent than AA RBC. Mechanically injured (sheared) AA RBC were also more adherent than control normal cells but less adherent than SS RBC. AS RBC did not differ significantly in their adhesive properties from normal RBC. Less-dense RBC were more adherent to EC than dense cells for normal, SS, and high-reticulocyte control RBC. The number of cells adherent at a given time during washout was a very strong function of wall shear rate. In addition, at all shear rates studied, the average velocity of individual SS RBC in the region near the EC surface was approximately half that of AA RBC at the same bulk volumetric flow rate through the flow chamber. These findings suggest that the increased adhesion of sickle RBC is at least partially related to the increased numbers of less-dense RBC present. Increased adherence of the less-dense cells to the EC lining vessel walls could contribute to microvascular occlusion by lengthening vascular transit times of other sickle cells. | Sickle cell disease (SCD) is characterized by microvascular occlusion mediated by adhesive interactions of sickle erythrocytes (SSRBCs) to the endothelium. Most in vitro flow adhesion assays measure SSRBC adhesion during continuous flow, although in vivo SSRBC adhesive interactions occur during pulsatile flow. Using a well-plate microfluidic flow adhesion system, we demonstrate that isolated SSRBCs adhere to vascular cell adhesion molecule (VCAM-1) at greater levels during pulsatile versus continuous flow. A significant increase in adhesive interactions was observed between all pulse frequencies 1 Hz to 2 Hz (60-120 beats/min) when compared to non-pulsatile flow. Adhesion of isolated SSRBCs and whole blood during pulsatile flow was unaffected by protein kinase A (PKA) inhibition, and exposure of SSRBCs to pulsatile flow did not affect the intrinsic adhesive properties of SSRBCs. The cell type responsible for increased adhesion of whole blood varied from patient to patient. We conclude that low flow periods of the pulse cycle allow more adhesive interactions between sickle erythrocytes and VCAM-1, and sickle erythrocyte adhesion in the context of whole blood may better reflect physiologic cellular interactions. The microfluidic flow adhesion bioassay used in this study may have applications for clinical assessment of sickle erythrocyte adhesion during pulsatile flow. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,691 |
To explore serum vaspin, leptin, and adiponectin levels and their correlation with insulin resistance (IR) in pregnant women with and without gestational diabetes mellitus (GDM) and healthy non-pregnant women. A total of 262 individuals, including pregnant women with GDM (n = 86), those without GDM (n = 92), and age-matched healthy non-pregnant women (n = 84) were enrolled in this case-control study. Vaspin, leptin, adiponectin, glucose, insulin, hemoglobin A1C (HbA1c), and lipid parameters were measured. The homeostasis model assessment-insulin resistance (HOMA-IR), quantitative insulin sensitivity check index, and body mass index were calculated. Data inferred higher concentrations of vaspin (2.72 ± 2.20 vs. 1.84 ± 1.57 vs. 0.81 ± 1.02) in GDM than during normal pregnancy and in non-pregnant women, higher leptin (23.42 ± 12.18 vs. 22.19 ± 10.55 vs. 12.10 ± 11.26), and lower adiponectin (4,164.83 ± 2,650.39 vs. 4,871.66 ± 2,803.51 vs. 7,202.85 ± 4,893.13) in GDM and normal pregnancy as compared to non-pregnant women (p < 0.05). Vaspin was positively correlated to leptin (r = 0.273, p = 0.012), HOMA-IR (r = 0.387, p = 0.000), and triglycerides (TG, r = 0.218, p = 0.046) in GDM. In addition, leptin was negatively correlated to adiponectin in GDM (r = -0.336, p = 0.002) and normal pregnancy (r = -0.256, p = 0.014). Furthermore, vaspin was significantly correlated to GDM and HOMA-IR, and the weight gain might play a vital role in the occurrence of GDM. During pregnancy, high vaspin concentration is significantly associated with IR in GDM. | AIMS ::: In this study, we investigated the effects of visceral adipose tissue-derived serpin (vaspin), a newly discovered adipocytokine, on nuclear factor-kappa B (NF-κB) and its downstream molecules in proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukine-1 (IL-1), stimulated human endothelial EA.hy926 cells to elucidate the role of vaspin in the inflammatory states of endothelium. ::: ::: ::: METHODS ::: A NF-κB luciferase reporter system was constructed and stably transfected into human endothelial cell line EA.hy926. Following transfection, EA.hy926 cells were pretreated with various concentrations of vaspin (0-320 ng/ml) before TNF-α and IL-1 stimulation. The transcription activity of NF-κB was determined using luciferase reporter assay. Expression levels of NF-κB downstream inflammatory cytokines, TNF-α, IL-1 and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Expressions of adhesion molecules and chemokines, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) were determined by quantitative real-time PCR (RT-PCR) and western blot in mRNA and protein levels, respectively. ::: ::: ::: RESULTS ::: Results showed that vaspin inhibited TNF-α and IL-1 mediated activation of NF-κB and its downstream molecules in a concentration-dependent manner (P<0.05). ::: ::: ::: CONCLUSIONS ::: We conclude that vaspin protected endothelial cells from proinflammatory cytokines induced inflammation by inhibition of NF-κB and its downstream molecules. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,692 |
Endoglin is a glycoprotein which is predominantly expressed on endothelial cells. It is upregulated under inflammatory conditions as well as in skin lesions where endothelial cell proliferation occurs. Endoglin has the capacity to bind transforming growth factor beta (TGF-beta) and can reduce the bioavailability of TGF-beta. TGF-beta has a growth-inhibiting effect on keratinocytes and a restraining influence on the extravasation of peripheral white blood cells. In order to find out how endoglin is expressed in the margin zone of psoriatic plaques and how it correlates with the appearance of an inflammatory infiltrate, punch biopsies were taken from the margin zone of actively spreading psoriatic plaques in 8 patients. Indirect immunoperoxidase staining was performed using PAL-E (vascular endothelium), PN-E2 (anti-endoglin) and T11 (T-lymphocytes). In all patients it was found that the appearance of parakeratosis correlated with a clear increase of PN-E2 expression. PAL-E and PN-E2 expression was assessed, using a 5-point scale. Thus a tendency to decreased PN-E2 expression in uninvolved skin compared to PAL-E expression was found within the margin zone (1.6 +/- 0.4 and 2.2 +/- 0.4, respectively), whereas in involved skin PN-E2 expression and PAL-E expression were in agreement (2.6 +/- 0.5 and 2.6 +/- 0.5 respectively), suggesting that in the overt plaque all endothelium is in a so-called activated state. Also correlating with PN-E2 expression was the appearance of a huge dermal lymphocytic infiltrate and epidermal T-lymphocytic expression. The present study lends further support for a permissive role of endoglin expression in the development of the psoriatic lesion. | The involvement of the vascular endothelium in a large number of diseases supports the importance of vascular-specific gene delivery for their treatment. The hereditary hemorrhagic telangiectasia type 1 is an example of a vascular inherited disease (OMIM 187300). This is an autosomal dominant vascular disorder originated by mutations in the endoglin gene and associated with frequent epistaxis, telangiectases, gastrointestinal bleedings, and arteriovenous malformations in brain, lung and liver. Here, we address for the first time the possibility of using in vivo gene transfer to target endoglin expression to the vasculature. The promoter of the endothelial gene, ICAM-2, was used to generate transgenic animals which demonstrated endothelial expression of endoglin. Next, the promoters of the human endothelial genes, endoglin and ICAM-2, were inserted upstream of the human endoglin cDNA, and the resulting constructs were systemically or locally delivered, demonstrating endoglin expression in the vessel walls of liver, lung and skin. These gene transfer experiments represent an initial step in the treatment of the hereditary hemorrhagic telangiectasia type 1 by gene therapy, and suggest that endoglin and ICAM-2 promoters can be used to deliver other genes to the endothelium specifically. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,693 |
Any condition that decreases blood volume, cardiac output, or peripheral vasomotor tone sufficiently to impair tissue perfusion can cause shock. The cause should be established so that specific therapy can be given, but in the meantime, general measures should be directed at shock itself. Besides fluid resuscitation, these include correction of acid-base imbalance and maximization of tissue oxygenation. If hypotension persists after adequate fluid replacement, vasopressor therapy is indicated. Various drugs are available, and the choice depends on the pharmacologic characteristics of the agent and the pathophysiologic process involved. | Despite advances in antimicrobial therapy and medical support, septic shock remains a leading cause of death. Emerging adjunctive therapy for septic shock can be divided into those directed against bacterial components, those directed against host-derived inflammatory-mediators and those designed to limit tissue damage. All trials of new adjunctive therapies for sepsis and septic shock conducted to data have failed to show efficacy. Therapies against endotoxin, tumour necrosis factor, interleukin-1 and platelet activating factor did not reduce mortality. Future effective therapies will probably use combination of agents depending upon the nature of the infection and the type of patient. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,694 |
The purpose of this study was to examine the lytic effect on human platelet preparations (washed, gel-filtered and dextran-isolated) of two sulfhydryl-activated bacterial protein toxins, streptolysin 0 and and alveolysin, and to compare their efficacy with that of other disruptive procedures (freezing and thawing, ultrasonic, mechanical, or nystatin-toluene treatment) as a method for the determination of various platelet enzyme activities. The enzymes assayed were alkaline and acid phosphatases, monoamine oxidase, phenolsulfotransferase, N-acetyltransferase, hydroxyindole-O-methyltransferase, glutathione peroxidase and lactate dehydrogenase. In all cases, the lowest activities were found after freezing and thawing and/or ultrasonic disruption. The highest activities were always observed in the platelet lysates obtained after toxin, and in some instances after nystatin-toluene treatment. Intermediate values were obtained for mechanical disruption. The -SH-activated cytolysins thus appear to be appropriate and gentle tools for the assay of platelet enzymes when compared to the physical or chemical procedures generally employed. | Postulating that serotonin, secreted from smoking-activated platelets, could be involved in smoking-induced vascular modifications, we studied 115 men distributed in smokers (S), former smokers (FS) and never smokers (NS). The platelet serotonin content was similar in S and NS but lower in FS. This was unexpected because the monoamine oxidase (MAO) activity, which catabolizes serotonin, was inhibited during smoking. However, the amount of platelet MAO was higher in S and FS than in NS. The persistent elevated MAO amount in FS prompted us to study the methylation of its gene promoter in an additional series of patients: it was markedly lower for S and FS vs. NS due to cigarette smoke-induced increase of nucleic acid demethylase activity. This smoking-induced demethylation of the MAO gene promoter, resulting in high MAO amount persisting long after quitting smoking, has cardiovascular consequences and could impact fields such as behavior, mental health, and cancer. Key words: smoking, serotonin, monoamine oxidase, gene methylation | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,695 |
Cell proliferation of carcinoma cells DLD-1 derived from colon cancer as measured by [ 3 H]thymidine incorporation was drastically reduced in the presence of 4-aminopyridine, an inhibitors of voltage-gated K + channel. A number of nonspecific K + channel inhibitors including TPeA, TEA, verapamil and diltiazem also inhibited [ 3 H]incorporation at the concentration reported to inhibit voltagegated K + channels. The presence of voltage-gated K + channels was confirmed by reverse transcription-PCR and cDNA sequencing. Charybdotoxin and iberiotoxin, inhibitors for Ca 2+ -sensitive K + channel, and glibenclamide, a specific inhibitor for ATP-sensitive K + channel, did not have effect on cell proliferation. These experiments suggested a critical role of voltage-gated K + channels in proliferation of colon cancer cells. Mechanism of action of K + channel activity in cell proliferation was explored by studying the relationship between the K + channel activity and Ca 2+ entry. The results from experiments indicated that K + channel inhibitors blocked [Ca 2+ ]i influx. Therefore, it is likely that K + channel activity may modulate Ca 2+ influx into colon cancer cells, and subsequently modulate the proliferation of these cells. | Xenopus retinal ganglion cell growth cones express various voltage-gated potassium (Kv) channels. We showed previously that 4-aminopyridine and tetraethylammonium have different effects on the outward currents of embryonic Xenopus retinal ganglion cells. Therefore, we asked whether these Kv channel inhibitors differentially regulate the response of retinal ganglion cell growth cones to extrinsic cues. First, we tested the role of Kv channels in axon extension mediated by a substrate bound cue and found that 4-aminopyridine blocked, whereas tetraethylammonium enhanced basal extension on laminin. Yet, when the growth cones were stimulated to extend with application of soluble growth factors, both inhibitors resulted in a return to the basal extension rates observed in the presence of laminin alone. Second, we asked if Kv channels modulate the response of retinal ganglion cell growth cones to a guidance cue, the chemorepellent fibroblast growth factor-2. When presented in a gradient to one side of the growth cone, fibroblast growth factor-2 repulsed retinal ganglion cell growth cones in the presence of 4-aminopyridine but not tetraethylammonium. These data argue that tetraethylammonium- and 4-aminopyridine-sensitive Kv channels differ in the manner by which they regulate the response of retinal ganglion cell axons to extension and guidance cues. Non-ratiometric calcium imaging indicated that differences in the ability of tetraethylammonium- and 4-aminopyridine-sensitive Kv channels to regulate calcium activity within the growth cone may underlie their unique modulation of growth cone behaviour. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,696 |
The dried blood spot (DBS) sampling has a lot of advantages in comparison with the “standard” venous blood collecting, such as small collection volume, painless and easy sample collection with minimal training required, stable and transportable at ambient temperatures, etc. The aim of this study was to determine the comparability of four different types of DBS sampling (HemaSpot™-HF Blood Collection Device, Whatman® 903 Protein Saver Snap Apart Card, card ImmunoHealth™, and glass fiber strip ImmunoHealth™) for analysis of the global metabolites profile. All the samples were collected from the same person at the same time and stored at room temperature for four weeks in order to exclude all possible deviations deriving from biological variances and to evaluate sample storage stability. Metabolome profiling by direct injection of a deproteinized capillary blood DBS sample into an electrospray ion source of a hybrid quadrupole time-of-flight mass spectrometer was used. Differences in the metabolomics profile were found between the different DBS collection materials, especially for ImmunoHealth™ card and ImmunoHealth™ glass fiber strip. However, our results indicate that the analytical performance of all tested DBS sampling materials showed consistent results overall detected metabolites and no dramatic changes between them in the metabolic composition during the storage time. | As more HIV-infected people gain access to antiretroviral therapy (ART), monitoring HIV drug resistance (HIVDR) becomes essential to combat both acquired and transmitted HIVDR. Studies have demonstrated dried blood spots (DBS) are a suitable alternative in HIVDR monitoring using DBS collected on Whatman 903 (W-903). In this study, we sought to evaluate two other commercially available filter papers, Ahlstrom 226 (A-226) and Munktell TFN (M-TFN), for HIVDR genotyping following ambient temperature storage. DBS were prepared from remnant blood specimens collected from 334 ART patients and stored at ambient temperature for a median time of 30 days. HIV-1 viral load was determined using NucliSENS EasyQ® HIV-1 v2.0 RUO test kits prior to genotyping of the protease and reverse transcriptase regions of the HIV-1 pol gene using an in-house assay. Among the DBS tested, 26 specimens had a viral load ≥ 1000 copies/mL in all three types of filter paper and were included in the genotyping analysis. Genotyping efficiencies were similar between DBS collected on W-903 (92.3%), A-226 (88.5%), and M-TFN (92.3%) filter papers (P = 1.00). We identified 50 DR-associated mutations in DBS collected on W-903, 33 in DBS collected on A-226, and 48 in DBS collected on M-TFN, resulting in mutation detection sensitivities of 66.0% for A-226 and 88.0% for M-TFN when compared to W-903. Our data indicate that differences among filter papers may exist at this storage condition and warrant further studies evaluating filter paper type for HIVDR monitoring. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,697 |
Preeclampsia (PE) is a pregnancy-specific multisystem disorder and is associated with maladaptation of the maternal cardiovascular system and abnormal placentation. One of the important characteristics in the pathophysiology of PE is a dysfunction of the placenta. Placental insufficiency is associated with poor trophoblast uterine invasion and impaired transformation of the uterine spiral arterioles to high capacity and low impedance vessels and/or abnormalities in the development of chorionic villi. Significant progress in identifying potential molecular targets in the pathophysiology of PE is underway. The human placenta is immunologically functional with the trophoblast able to generate specific and diverse innate immune-like responses through their expression of multimeric self-assembling protein complexes, termed inflammasomes. However, the type of response is highly dependent upon the stimuli, the receptor(s) expressed and activated, the downstream signaling pathways involved, and the timing of gestation. Recent findings highlight that inflammasomes can act as a molecular link for several components at the syncytiotrophoblast surface and also in maternal blood thereby directly influencing each other. Thus, the inflammasome molecular platform can promote adverse inflammatory effects when chronically activated. This review highlights current knowledge in placental inflammasome expression and activity in PE-affected pregnancies, and consequently, vascular dysfunction in PE that must be addressed as an interdependent interactive process. | Reductions in uterine perfusion pressure (RUPP) in pregnant rats is associated with increased tumor necrosis factor-alpha (TNF-alpha). This study was designed to determine the role of endogenous TNF-alpha in mediating changes in arterial pressure and endothelin-1 (ET-1) in RUPP rats. To achieve this goal we examined the effect of RUPP in the presence and absence of a TNF-alpha-soluble receptor, etanerecept (0.4 mg/kg). Mean arterial pressure increased from 102+/-1 mm Hg in normal pregnant (NP) rats to 134+/-3 mm Hg (P<0.05) in RUPP rats. Serum TNF-alpha increased to 40+/-7.6 pg/mL in RUPP rats (n=24) versus 14.8+/-3.3 pg/mL (n=16; P<0.05) in NP rats. Administration of etanerecept decreased TNF-alpha in RUPP rats (n=20) to 17.2+/-3 pg/mL and mean arterial pressure to 118+/-2 mm Hg (P<0.05). Tissue ET-1 decreased in etanerecept-treated RUPP rats compared with control RUPP rats. The direct effect of TNF-alpha blockade on endothelial activation in response to placental ischemia was examined in human umbilical vein endothelial cells. ET-1 secreted from human umbilical vein endothelial cells treated with RUPP serum was 59.2+16 pg/mg and decreased when etanerecept was added to the medium with RUPP serum (7.60+/-0.77 pg/mg), as well as in response to serum from etanerecept-treated RUPP rats (7.30+/-0.55 pg/mg; P<0.001). ET-1 secreted from human umbilical vein endothelial cells was 15.6+/-2 pg/mg when treated with NP serum. These data support the hypothesis that endogenous TNF-alpha is an important stimulus for ET-1 in response to placental ischemia and is important in mediating endothelial cell activation and hypertension during pregnancy. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,698 |
To develop an estimation method of gadolinium magnetic resonance imaging (MRI) contrast agents, the effect of concentration of Gd compounds on the ESR spectrum of nitroxyl radical was examined. A solution of either 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPONE) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) was mixed with a solution of Gd compound and the ESR spectrum was recorded. Increased concentration of gadolinium-diethylenetriamine pentaacetic acid chelate (Gd-DTPA), an MRI contrast agent, increased the peak-to-peak line widths of ESR spectra of the nitroxyl radicals, in accordance with a decrease of their signal heights. A linear relationship was observed between concentration of Gd-DTPA and line width of ESR signal, up to approximately 50 mmol/L Gd-DTPA, with a high correlation coefficient. Response of TEMPONE was 1.4-times higher than that of TEMPOL as evaluated from the slopes of the lines. The response was slightly different among Gd compounds; the slopes of calibration curves for acua[N,N-bis[2-[(carboxymethyl)[(methylcarbamoyl)methyl]amino]ethyl]glycinato(3-)]gadolinium hydrate (Gd-DTPA-BMA) (6.22 μT·L/mmol) and gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid chelate (Gd-DOTA) (6.62 μT·L/mmol) were steeper than the slope for Gd-DTPA (5.45 μT·L/mmol), whereas the slope for gadolinium chloride (4.94 μT·L/mmol) was less steep than that for Gd-DTPA. This method is simple to apply. The results indicate that this method is useful for rough estimation of the concentration of Gd contrast agents if calibration is carried out with each standard compound. It was also found that the plot of the reciprocal square root of signal height against concentrations of contrast agents could be useful for the estimation if a constant volume of sample solution is taken and measured at the same position in the ESR cavity every time. | The purpose of this paper is to describe some of the areas where electron paramagnetic resonance (EPR) has provided unique information to MRI developments. The field of application mainly encompasses the EPR characterization of MRI paramagnetic contrast agents (gadolinium and manganese chelates, nitroxides) and superparamagnetic agents (iron oxide particles). The combined use of MRI and EPR has also been used to qualify or disqualify sources of contrast in MRI. Illustrative examples are presented with attempts to qualify oxygen sensitive contrast (i.e. T1 - and T2 *-based methods), redox status or melanin content in tissues. Other areas are likely to benefit from the combined EPR/MRI approach, namely cell tracking studies. Finally, the combination of EPR and MRI studies on the same models provides invaluable data regarding tissue oxygenation, hemodynamics and energetics. Our description will be illustrative rather than exhaustive to give to the readers a flavour of 'what EPR can do for MRI'. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,699 |
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