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PMID:16481 | Studies on the pathogenesis of diet-induced dog gallstones. | Experimental diet-induced dog gallstones contained mainly protein, mucous substances, bile salts, bilirubin, an insoluble pigment which formed an insoluble black residue after acid hydrolysis, and only traces of cholesterol. Added dietary cholesterol was necessary to pigmented gallstone production and led to hypercholesterolemia. In bile, the ratio of cholesterol to bile salts was increased, but phospholipids were increased and cholesterol insolubility was not found. Dry weight, osmolality, and concentration of sodium and potassium in bile were reduced, but were not considered sufficient to influence micelle formation or lipid-pigment solubility. Taurine was reduced in serum and bile and unconjugated bile acids appeared in gallbladder bile; the pKa of these acids is near the pH of bile in these animals and may have caused precipitation of bile acids, accounting for their presence in the stones. Bile cultures were sterile. Total bilirubin content was unaltered but the methods used did not exclude the presence of unconjugated bilirubin as a potential cause of pigment precipitation in aqueous bile. Increased numbers of secretory vesicles occurred in gallbladder epithelium and large amounts of mucus were in the epithelial crypts. These observations suggest that bile proteins or mucous substances are important to lithogenesis in this model. | Studies on the pathogenesis of diet-induced dog gallstones. Experimental diet-induced dog gallstones contained mainly protein, mucous substances, bile salts, bilirubin, an insoluble pigment which formed an insoluble black residue after acid hydrolysis, and only traces of cholesterol. Added dietary cholesterol was necessary to pigmented gallstone production and led to hypercholesterolemia. In bile, the ratio of cholesterol to bile salts was increased, but phospholipids were increased and cholesterol insolubility was not found. Dry weight, osmolality, and concentration of sodium and potassium in bile were reduced, but were not considered sufficient to influence micelle formation or lipid-pigment solubility. Taurine was reduced in serum and bile and unconjugated bile acids appeared in gallbladder bile; the pKa of these acids is near the pH of bile in these animals and may have caused precipitation of bile acids, accounting for their presence in the stones. Bile cultures were sterile. Total bilirubin content was unaltered but the methods used did not exclude the presence of unconjugated bilirubin as a potential cause of pigment precipitation in aqueous bile. Increased numbers of secretory vesicles occurred in gallbladder epithelium and large amounts of mucus were in the epithelial crypts. These observations suggest that bile proteins or mucous substances are important to lithogenesis in this model. | [
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PMID:16482 | Absorption of short-chain fatty acids from the human ileum. | Acetate, propionate, and n-butyrate are the major short-chain fatty acid (SCFA) anions in the gastrointestinal tract of animal and man, accounting for 90% of total SCFA in stool water. Their absorption from the human ileum was investigated in 8 volunteer subjects by the triple-lumen perfusion technique. Each test solution contained one of the SCFAs at a concentration of 0-100 mM; sodium, potassium, and bicarbonate concentrations were kept constant, as were pH and osmolality. Absorption of each SCFA was found to be rate-limited with an apparent K'm between 22 and 27 mM and a calculated Vmax between 0.54 and 0.82 mmol/hr cm. Water, sodium, and chloride transport were not affected by substantial rates of SCFA absorption. Rather, significant stimulation of calculated bicarbonate secretion and a rise in intraluminal pH were consistently observed. The results are compatible with either of two mechanisms for SCFA absorption: an anion exchange between bicarbonate (or hydroxyl) and SCFA ions, or protonation of the SCFA anion at the mucosal surface followed by simple diffusion of nonionized SCFA into the absorbing cell. | Absorption of short-chain fatty acids from the human ileum. Acetate, propionate, and n-butyrate are the major short-chain fatty acid (SCFA) anions in the gastrointestinal tract of animal and man, accounting for 90% of total SCFA in stool water. Their absorption from the human ileum was investigated in 8 volunteer subjects by the triple-lumen perfusion technique. Each test solution contained one of the SCFAs at a concentration of 0-100 mM; sodium, potassium, and bicarbonate concentrations were kept constant, as were pH and osmolality. Absorption of each SCFA was found to be rate-limited with an apparent K'm between 22 and 27 mM and a calculated Vmax between 0.54 and 0.82 mmol/hr cm. Water, sodium, and chloride transport were not affected by substantial rates of SCFA absorption. Rather, significant stimulation of calculated bicarbonate secretion and a rise in intraluminal pH were consistently observed. The results are compatible with either of two mechanisms for SCFA absorption: an anion exchange between bicarbonate (or hydroxyl) and SCFA ions, or protonation of the SCFA anion at the mucosal surface followed by simple diffusion of nonionized SCFA into the absorbing cell. | [
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|
PMID:16483 | Esophageal intraluminal pH recording in the assessment of gastroesophageal reflux and its consequences. | Intraluminal pH in the lower esophagus has been recorded during a 3-hr period following a ligh meal and a consecutive 12-hr nocturnal period in 20 patients with typical symptoms and radiological evidence of gastroesophageal reflux and in 10 patients without such signs of reflux. Evidence of acid reflux was obtained in 3 of the patients without reflux during the postcibal period but in only one during the 12-hr nocturnal period. In contrast all except one of the 20 patients who had evidence of reflux showed spells of high acidity both in the postcibal and nocturnal periods. There was no clear correlation between the frequency of paf high acidity in the nocturnal period. Those patients with endoscopic evidence of severe esophagitis showed a significantly longer duration of high esophageal acidity in the nocturnal period. We conclude that nocturnal exposure of the esophageal mucosa to acid is a major factor in the causation of reflux esophagitis. | Esophageal intraluminal pH recording in the assessment of gastroesophageal reflux and its consequences. Intraluminal pH in the lower esophagus has been recorded during a 3-hr period following a ligh meal and a consecutive 12-hr nocturnal period in 20 patients with typical symptoms and radiological evidence of gastroesophageal reflux and in 10 patients without such signs of reflux. Evidence of acid reflux was obtained in 3 of the patients without reflux during the postcibal period but in only one during the 12-hr nocturnal period. In contrast all except one of the 20 patients who had evidence of reflux showed spells of high acidity both in the postcibal and nocturnal periods. There was no clear correlation between the frequency of paf high acidity in the nocturnal period. Those patients with endoscopic evidence of severe esophagitis showed a significantly longer duration of high esophageal acidity in the nocturnal period. We conclude that nocturnal exposure of the esophageal mucosa to acid is a major factor in the causation of reflux esophagitis. | [
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|
PMID:16484 | Effects of parenteral secretin--cholecystokinin and of duodenal acid perfusion on gastric secretion in duodenal ulcer patients. | The effect of parenteral secretin-cholecystokinin and duodenal acid perfusion on broth-stimulated gastric acid secretion was studied in 11 duodenal ulcer patients. Statistically significant inhibition occurred in both experimental conditions. The effect of secretin-cholecystokinin was more marked than the effect of duodenal acid perfusion. A poorly responsive subgroup of patients appeared to be responsible for the diminished inhibitory effect of duodenal acid perfusion. In this poorly responsive group there was a diminished duodenal volume response as well as diminished duodenal acid clearing. We conclude that there may exist a diminished release of gastrointestinal hormones such as secretin and cholecystokinin in certain duodenal ulcer patients. | Effects of parenteral secretin--cholecystokinin and of duodenal acid perfusion on gastric secretion in duodenal ulcer patients. The effect of parenteral secretin-cholecystokinin and duodenal acid perfusion on broth-stimulated gastric acid secretion was studied in 11 duodenal ulcer patients. Statistically significant inhibition occurred in both experimental conditions. The effect of secretin-cholecystokinin was more marked than the effect of duodenal acid perfusion. A poorly responsive subgroup of patients appeared to be responsible for the diminished inhibitory effect of duodenal acid perfusion. In this poorly responsive group there was a diminished duodenal volume response as well as diminished duodenal acid clearing. We conclude that there may exist a diminished release of gastrointestinal hormones such as secretin and cholecystokinin in certain duodenal ulcer patients. | [
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|
PMID:16488 | Antimicrobial and other properties of a new stabilized alkaline glutaraldehyde disinfectant/sterilizer. | The properties of stabilized alkaline 2% glutaraldehyde solution (SGS) are discussed. SGS is discussed with regard to its chemistry, antimicrobial properties, organic soil resistance, toxicity, corrosivity and chemical stability. SGS retains the maximum antimicrobial activity of alkaline glutaraldehyde solutions and the chemical stability heretofore observed only with acidic glutaraldehyde solutions. These improvements, along with the inherent resistance of glutaraldehyde to neutralization by organic soil, allow SGS to be continuously used for 14 days in situations of high dilution, or 28 days in situations of low dilution. | Antimicrobial and other properties of a new stabilized alkaline glutaraldehyde disinfectant/sterilizer. The properties of stabilized alkaline 2% glutaraldehyde solution (SGS) are discussed. SGS is discussed with regard to its chemistry, antimicrobial properties, organic soil resistance, toxicity, corrosivity and chemical stability. SGS retains the maximum antimicrobial activity of alkaline glutaraldehyde solutions and the chemical stability heretofore observed only with acidic glutaraldehyde solutions. These improvements, along with the inherent resistance of glutaraldehyde to neutralization by organic soil, allow SGS to be continuously used for 14 days in situations of high dilution, or 28 days in situations of low dilution. | [
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|
PMID:16489 | Propoxyphene: a review. | A critical analysis of information on propoxyphene that has been published since the drug's introduction is presented. Propoxyphene is discussed with regard to its chemistry, metabolism and pharmacokinetics, analgesic efficacy, analgesic efficacy of combination products, nonanalgesic uses, adverse effects, overdosage, and dependence and abuse. Both the hydrochloride and napsylate salts are covered. It is doubtful that propoxyphene hydrochloride 65 mg provides an analgesic effect equal to that of aspirin 650 mg. There is no conclusive evidence that combinations of propoxyphene with other analgesics are more effective than propoxyphene or other analgesics alone. | Propoxyphene: a review. A critical analysis of information on propoxyphene that has been published since the drug's introduction is presented. Propoxyphene is discussed with regard to its chemistry, metabolism and pharmacokinetics, analgesic efficacy, analgesic efficacy of combination products, nonanalgesic uses, adverse effects, overdosage, and dependence and abuse. Both the hydrochloride and napsylate salts are covered. It is doubtful that propoxyphene hydrochloride 65 mg provides an analgesic effect equal to that of aspirin 650 mg. There is no conclusive evidence that combinations of propoxyphene with other analgesics are more effective than propoxyphene or other analgesics alone. | [
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|
PMID:16490 | Immune complexes in hepatitis B antigen-associated periarteritis nodosa. Detection by antibody-dependent cell-mediated cytotoxicity and the Raji cell assay. | A subpopulation of peripheral blood lymphocytes with the ability to lyse target cells coated with specific antibody (antibody-dependent cell-mediated cytotoxicity, ADCC) was serially studied in a patient with hepatitis B antigen-associated periarteritis nodosa. The effector lymphocytes possess FC and complement receptors but do not require complement for functional activity. We found that the patient's ADCC was decreased during periods of disease activity and was almost normal during remission. The patient's serum could block ADCC in normal lymphocytes, and the blocking ability correlated with the concentration of immune complexes as determined by the Raji cell assay (a radioimmunoassay using complement receptors on human cultured lymphoblastoid cells). The concentration of immune complexes and the ADCC blocking ability of ther serum both correlated with disease activity. Serum from five other patients with active vasculitis was found to contain significant amounts of immune complexes and was able to block normal ADCC. It appears that the ADCC assay can be used to detect the presence of circulating immune complexes and to monitor disease activity in periarteritis nodosa. | Immune complexes in hepatitis B antigen-associated periarteritis nodosa. Detection by antibody-dependent cell-mediated cytotoxicity and the Raji cell assay. A subpopulation of peripheral blood lymphocytes with the ability to lyse target cells coated with specific antibody (antibody-dependent cell-mediated cytotoxicity, ADCC) was serially studied in a patient with hepatitis B antigen-associated periarteritis nodosa. The effector lymphocytes possess FC and complement receptors but do not require complement for functional activity. We found that the patient's ADCC was decreased during periods of disease activity and was almost normal during remission. The patient's serum could block ADCC in normal lymphocytes, and the blocking ability correlated with the concentration of immune complexes as determined by the Raji cell assay (a radioimmunoassay using complement receptors on human cultured lymphoblastoid cells). The concentration of immune complexes and the ADCC blocking ability of ther serum both correlated with disease activity. Serum from five other patients with active vasculitis was found to contain significant amounts of immune complexes and was able to block normal ADCC. It appears that the ADCC assay can be used to detect the presence of circulating immune complexes and to monitor disease activity in periarteritis nodosa. | [
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|
PMID:16491 | Bilateral atrial myxomas with multiple arterial aneurysms--a syndrome mimicking polyarteritis nodosa. | This patient, previously described as having polyarteritis nodosa with multiple aneurysms shown by angiography, was recently found to have bilateral atrial myxomas. The angiographic demonstration of multiple cerebral aneurysms has been described in a few cases of left atrial myxoma. This uncommon tumor is also accompanied by "constitutional" manifestations. Thus, a syndrome mimicking polyarteritis nodosa may be produced. Cardiac myxoma should be borne in mind in conditions with multifocal organic involvement, and they should be included in the list of conditions causing multiple arterial aneurysms. | Bilateral atrial myxomas with multiple arterial aneurysms--a syndrome mimicking polyarteritis nodosa. This patient, previously described as having polyarteritis nodosa with multiple aneurysms shown by angiography, was recently found to have bilateral atrial myxomas. The angiographic demonstration of multiple cerebral aneurysms has been described in a few cases of left atrial myxoma. This uncommon tumor is also accompanied by "constitutional" manifestations. Thus, a syndrome mimicking polyarteritis nodosa may be produced. Cardiac myxoma should be borne in mind in conditions with multifocal organic involvement, and they should be included in the list of conditions causing multiple arterial aneurysms. | [
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|
PMID:16492 | Gonadotropin receptors in human corpora lutea of the menstrual cycle and pregnancy. | Binding of 125I-human choriogonadotropin (hCG) to homogenates of corpora lutea of the menstrual cycle and pregnancy was examined. While corpora lutea of the menstrual cycle bound 125I-hCG, most of the corpora lutea of pregnancy from six to 34 weeks' gestation bound little or none of the added 125 I-hCG. Further exploration into various possibilities for the above findings led to the conclusion that these corpora lutea either contain very few gonadotropin receptors or lack them altogether. The selected properties of gonadotropin receptors in corpora lutea of the cycle were studied. The apparent dissociation constant for binding was about the same (2.6 to 3.8 x 10-10M) in all but one corpus luteum. In this one sample the constant was three- to five-fold higher (1.3 x 10-9M). The binding was quite rapid and reversible, and it exhibited dependence on the amount of 125I-hCG, homogenate protein, pH of the incubation media, and duration of incubation. hCG and human lutropin (hLH') competed for 125I-hCG binding, but hCG subunits (alpha and beta), human follitropin, and ovine prolactin did not. Although hCG and hLH were parallel in inhibiting 125I-hCG binding, hLH was found to be relatively less effective. The studies with various enzymes revealed that gonadotropin receptors are protein in nature. | Gonadotropin receptors in human corpora lutea of the menstrual cycle and pregnancy. Binding of 125I-human choriogonadotropin (hCG) to homogenates of corpora lutea of the menstrual cycle and pregnancy was examined. While corpora lutea of the menstrual cycle bound 125I-hCG, most of the corpora lutea of pregnancy from six to 34 weeks' gestation bound little or none of the added 125 I-hCG. Further exploration into various possibilities for the above findings led to the conclusion that these corpora lutea either contain very few gonadotropin receptors or lack them altogether. The selected properties of gonadotropin receptors in corpora lutea of the cycle were studied. The apparent dissociation constant for binding was about the same (2.6 to 3.8 x 10-10M) in all but one corpus luteum. In this one sample the constant was three- to five-fold higher (1.3 x 10-9M). The binding was quite rapid and reversible, and it exhibited dependence on the amount of 125I-hCG, homogenate protein, pH of the incubation media, and duration of incubation. hCG and human lutropin (hLH') competed for 125I-hCG binding, but hCG subunits (alpha and beta), human follitropin, and ovine prolactin did not. Although hCG and hLH were parallel in inhibiting 125I-hCG binding, hLH was found to be relatively less effective. The studies with various enzymes revealed that gonadotropin receptors are protein in nature. | [
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|
PMID:16493 | Effect of fenoterol (Th1165a) infusion on uterine and umbilical blood flow in pregnant sheep. | The effect of fenoterol (Th1165a) upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) was investigated in near-term, nonlaboring chronic sheep preparations. During intravenous fenoterol infusions to the ewe in either incremental doses from 0.025 to 0.200 microng per kilogram per minute or constant infusions of 0.025 microng per kilogram per minute for 120 minutes. UtBF and UmBF did not change significantly. Dose-related maternal tachycardia, hyperglycemia, and relative acidemia occurred, but there were no significant changes in mean maternal and fetal arterial pressures or fetal heart rate. The simultaneous infusion of propranolol (2 microng per kilogram per minute) with fenoterol (0.200 microng per kilogram per minute) blocked the maternal tachycardia but resulted in a significant decrease in UmBF and a significant increase in UtBF. In all of the maternal infusions. UtBF significantly rose and plateaued up to 14 per cent above the control level during the 120 minute recovery period after infusion. A non-beta-adrenergic effect of fenoterol is suggested as the cause of this UtBF increase. | Effect of fenoterol (Th1165a) infusion on uterine and umbilical blood flow in pregnant sheep. The effect of fenoterol (Th1165a) upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) was investigated in near-term, nonlaboring chronic sheep preparations. During intravenous fenoterol infusions to the ewe in either incremental doses from 0.025 to 0.200 microng per kilogram per minute or constant infusions of 0.025 microng per kilogram per minute for 120 minutes. UtBF and UmBF did not change significantly. Dose-related maternal tachycardia, hyperglycemia, and relative acidemia occurred, but there were no significant changes in mean maternal and fetal arterial pressures or fetal heart rate. The simultaneous infusion of propranolol (2 microng per kilogram per minute) with fenoterol (0.200 microng per kilogram per minute) blocked the maternal tachycardia but resulted in a significant decrease in UmBF and a significant increase in UtBF. In all of the maternal infusions. UtBF significantly rose and plateaued up to 14 per cent above the control level during the 120 minute recovery period after infusion. A non-beta-adrenergic effect of fenoterol is suggested as the cause of this UtBF increase. | [
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|
PMID:16494 | The effect of umbilical vein occlusion on fetal oxygenation, cardiovascular parameters, and fetal electroencephalogram. | In 11 fetal sheep experiments, the blood pressure in the fetal aorta (FA) and in the umbilical vein (UV) was measured following umbilical vein occlusion (UVO), as was the fetal heart rate (FHR), pH, Pco2, and oxygen saturation (So2) in both fetal vessels, and umbilical blood flow (Qumb) of the common UV. The fetal electroencephalogram was recorded continuously throughout the experiment. The results (No. = 17) were grouped according to the response of FA So2 into moderate (So2greater than40 per cent, mean 49.8, S.D. 6.3, and severe So2less than40 per cent, mean 20.4, S.D. 9.2). After 8 to 10 seconds, the fetal blood pressure in FA increased. Umbilical vein blood pressure increased to 25 mm. Hg (S.D. 8) and 35 mm. Hg (S.D. 9) in the moderate and severe groups, respectively. As a result of the decreased perfusion pressure (FA-UV blood pressure) across the fetal side of the placenta, the Qumb fell from 147 ml. per kilogram per minute (S.D. 57) and 30 ml. per kilogram per minute (S.D. 55) to 84 ml. per kilogram per minute (S.D. 48) and 120 ml. per kilogram per minute (S.D.22), respectively. The fall in FA So2 was related to the decrease in Qumb: FA So2=37.6 x log Qumb - 22.8 (2alphaless than 0.001). There was a mild decrease in So2 from 70 to 55 per cent when Qumb fell from 250 to 120 ml. per kilogram per minute. Below 80 to 120ml. per kilogram per minute, the fall in FA So2 was almost linear. The So2 in the UV remained constant so that arteriovenous difference for oxygen (AV Do2) increased. Oxygen consumption decreased almost linearly when Qumb fell below 80 to 120 ml. per kilogram per minute. The fetal electroencephalogram showed no significant change in voltage and the faster activities. From these observations, it is concluded that a decrease in Qumb following UVO jeopardizes the fetus only if a critical Qumb of 80 to 120 ml. per kilogram per minute and fetal artery So2 of 50 to 60 per cent is achieved. | The effect of umbilical vein occlusion on fetal oxygenation, cardiovascular parameters, and fetal electroencephalogram. In 11 fetal sheep experiments, the blood pressure in the fetal aorta (FA) and in the umbilical vein (UV) was measured following umbilical vein occlusion (UVO), as was the fetal heart rate (FHR), pH, Pco2, and oxygen saturation (So2) in both fetal vessels, and umbilical blood flow (Qumb) of the common UV. The fetal electroencephalogram was recorded continuously throughout the experiment. The results (No. = 17) were grouped according to the response of FA So2 into moderate (So2greater than40 per cent, mean 49.8, S.D. 6.3, and severe So2less than40 per cent, mean 20.4, S.D. 9.2). After 8 to 10 seconds, the fetal blood pressure in FA increased. Umbilical vein blood pressure increased to 25 mm. Hg (S.D. 8) and 35 mm. Hg (S.D. 9) in the moderate and severe groups, respectively. As a result of the decreased perfusion pressure (FA-UV blood pressure) across the fetal side of the placenta, the Qumb fell from 147 ml. per kilogram per minute (S.D. 57) and 30 ml. per kilogram per minute (S.D. 55) to 84 ml. per kilogram per minute (S.D. 48) and 120 ml. per kilogram per minute (S.D.22), respectively. The fall in FA So2 was related to the decrease in Qumb: FA So2=37.6 x log Qumb - 22.8 (2alphaless than 0.001). There was a mild decrease in So2 from 70 to 55 per cent when Qumb fell from 250 to 120 ml. per kilogram per minute. Below 80 to 120ml. per kilogram per minute, the fall in FA So2 was almost linear. The So2 in the UV remained constant so that arteriovenous difference for oxygen (AV Do2) increased. Oxygen consumption decreased almost linearly when Qumb fell below 80 to 120 ml. per kilogram per minute. The fetal electroencephalogram showed no significant change in voltage and the faster activities. From these observations, it is concluded that a decrease in Qumb following UVO jeopardizes the fetus only if a critical Qumb of 80 to 120 ml. per kilogram per minute and fetal artery So2 of 50 to 60 per cent is achieved. | [
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PMID:16495 | Cardiovascular effects of fever in the ewe and fetal lamb. | Ewes carrying fetuses with permanently implanted cannulas developed fevers following intravenous injections of bacterial pyrogen (1 microng). During the rising phase of the fever, maternal heart rate increased, but no consistent changes in mean arterial blood pressure (MABP), arterial pH, PO2, or PCO2 were observed during the course of the fever. Fetal temperature, which was initially 0.3 to 0.8 degrees C. higher than maternal temperature rose in parallel with the ewe's temperature. During the maternal fever, fetal MABP, pH, PO2, and PCO2 remained unchanged, but on several occasions the fetal heart rate developed irregularities that persisted after the fever had subsided. These observations suggest that maternal fever does not appear to have adverse effects on fetal oxygenation but has a variable effect on cardiovascular function. | Cardiovascular effects of fever in the ewe and fetal lamb. Ewes carrying fetuses with permanently implanted cannulas developed fevers following intravenous injections of bacterial pyrogen (1 microng). During the rising phase of the fever, maternal heart rate increased, but no consistent changes in mean arterial blood pressure (MABP), arterial pH, PO2, or PCO2 were observed during the course of the fever. Fetal temperature, which was initially 0.3 to 0.8 degrees C. higher than maternal temperature rose in parallel with the ewe's temperature. During the maternal fever, fetal MABP, pH, PO2, and PCO2 remained unchanged, but on several occasions the fetal heart rate developed irregularities that persisted after the fever had subsided. These observations suggest that maternal fever does not appear to have adverse effects on fetal oxygenation but has a variable effect on cardiovascular function. | [
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|
PMID:16497 | Na+-K+-ATPase inhibition stimulates PGE release in guinea pig taenia coli. | Inhibition of the plasma membrane enzyme Na+-K+-ATPase by ouabain zero extracellular K+, or low extracellular Na+, markedly augmented prostaglandin E release from the guinea pig taenia coli. Data suggest this phenomenon may be linked directly to Na+-K+-ATPase or Na+ pump activities, or changes in intracellular K+ concentration. The augmented prostaglandin E release was not due to changes in intracellular Na+, Ca2+, pH, or membrane potential, resulting from Na+ pump inhibition. The characteristics of the plasma membrane may exert a control on prostaglandin E release in this smooth muscle. | Na+-K+-ATPase inhibition stimulates PGE release in guinea pig taenia coli. Inhibition of the plasma membrane enzyme Na+-K+-ATPase by ouabain zero extracellular K+, or low extracellular Na+, markedly augmented prostaglandin E release from the guinea pig taenia coli. Data suggest this phenomenon may be linked directly to Na+-K+-ATPase or Na+ pump activities, or changes in intracellular K+ concentration. The augmented prostaglandin E release was not due to changes in intracellular Na+, Ca2+, pH, or membrane potential, resulting from Na+ pump inhibition. The characteristics of the plasma membrane may exert a control on prostaglandin E release in this smooth muscle. | [
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PMID:16498 | Vitamin A1 intestinal absorption in vivo: influence of luminal factors on transport. | Intestinal absorption of [3H]retinol was studied in the unanesthetized rat. Luminal perfusate was recirculated through isolated intestinal segments with intact vascular and lymphatic circulation. Apparent saturation kinetics were found in physiological concentrations of retinol, whereas a linear relationship between the concentration and absorption rate was found at pharmacological concentrations of retinol in the perfusate. In physiological concentrations, retinol uptake in vitro by everted gut sacs was unaffected by anoxia or metabolic inhibitors and uncouplers. In vivo retinol absorption rate was decreased when sodium taurocholate concentration was raised above 5 mM, or when 2.5 mM linoleic or linolenic acids were added to the perfusate. Absorption increased markedly as the thickness of the unstirred water layer was diminished. Variations in perfusate pH from 4.5 to 8.6 did not change the retinol absorption rate. In vivo absorption of retinol in physiological concentrations is mediated by a saturable, carrier-mediated passive absorption mechanism modified by the presence of fatty acids of varying chain length. | Vitamin A1 intestinal absorption in vivo: influence of luminal factors on transport. Intestinal absorption of [3H]retinol was studied in the unanesthetized rat. Luminal perfusate was recirculated through isolated intestinal segments with intact vascular and lymphatic circulation. Apparent saturation kinetics were found in physiological concentrations of retinol, whereas a linear relationship between the concentration and absorption rate was found at pharmacological concentrations of retinol in the perfusate. In physiological concentrations, retinol uptake in vitro by everted gut sacs was unaffected by anoxia or metabolic inhibitors and uncouplers. In vivo retinol absorption rate was decreased when sodium taurocholate concentration was raised above 5 mM, or when 2.5 mM linoleic or linolenic acids were added to the perfusate. Absorption increased markedly as the thickness of the unstirred water layer was diminished. Variations in perfusate pH from 4.5 to 8.6 did not change the retinol absorption rate. In vivo absorption of retinol in physiological concentrations is mediated by a saturable, carrier-mediated passive absorption mechanism modified by the presence of fatty acids of varying chain length. | [
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PMID:16499 | Effect of chronic furosemide administration on hydrogen and sodium excretion in the dog. | Studies were performed to evaluate the effects of the chronic administration of furosemide on hydrogen and electrolyte excretion in dogs on a normal electrolyte diet and in the absence of electrolyte or volume depletion. Control daily excretion in five dogs averaged 64 meq for Na, 51 meq for K, 66 meq for Cl, and 17 meq for net H. Furosemide, 40 mg, in the drinking water 3 times daily was given for 4 days. On day 1 Na excretion averaged 128 meq, but thereafter was not significantly different from control levels. Over 4 days cumulative net H excretion increased 63.6 meq and plasma HCO3 rose 6.6 meq/liter. The same dogs were restudied by the same protocol except that, to obviate electrolyte depletion, NaCl and KCl were administered daily in quantities sufficient to replace urinary losses. All dogs remained in positive Na, K, and Cl balance. Body weight, hematocrit, plasma albumin, creatinine, and plasma renin activity were unchanged, indicating the absence of electrolyte or volume depletion. Nonetheless, cumulative net H excretion increased 61.2 meq and plasma HCO3 increased 4.3 meq/liter. Two adrenalectomized dogs receiving steroid replacement showed similar changes in net H excretion and plasma HCO3. These experiments suggest that chronic furosemide administration may enhance H excretion and generate alkalosis even in the absence of volume or electrolyte depletion and without increased aldosterone secretion. | Effect of chronic furosemide administration on hydrogen and sodium excretion in the dog. Studies were performed to evaluate the effects of the chronic administration of furosemide on hydrogen and electrolyte excretion in dogs on a normal electrolyte diet and in the absence of electrolyte or volume depletion. Control daily excretion in five dogs averaged 64 meq for Na, 51 meq for K, 66 meq for Cl, and 17 meq for net H. Furosemide, 40 mg, in the drinking water 3 times daily was given for 4 days. On day 1 Na excretion averaged 128 meq, but thereafter was not significantly different from control levels. Over 4 days cumulative net H excretion increased 63.6 meq and plasma HCO3 rose 6.6 meq/liter. The same dogs were restudied by the same protocol except that, to obviate electrolyte depletion, NaCl and KCl were administered daily in quantities sufficient to replace urinary losses. All dogs remained in positive Na, K, and Cl balance. Body weight, hematocrit, plasma albumin, creatinine, and plasma renin activity were unchanged, indicating the absence of electrolyte or volume depletion. Nonetheless, cumulative net H excretion increased 61.2 meq and plasma HCO3 increased 4.3 meq/liter. Two adrenalectomized dogs receiving steroid replacement showed similar changes in net H excretion and plasma HCO3. These experiments suggest that chronic furosemide administration may enhance H excretion and generate alkalosis even in the absence of volume or electrolyte depletion and without increased aldosterone secretion. | [
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PMID:16500 | Effect of parathyroid hormone on urinary acidification. | The effect of parathyroid hormone (PTH) administration on urinary acidification was studied in intact and thyroparathyroidectomized dogs. PTH administration resulted in a significant increase in urine pH and HCO3 excretion. In dogs with maximally acid urine caused by Na2SO4 infusion PTH administration also led to a significant increase in urine pH and to a decrease in ammonium excretion. To examine the effect of PTH on H+ secretion in the distal nephron we measured the urine-blood (U-B) PCO2 gradient in dogs with maximally alkaline urine (urine pH greater than 7.8) before and after PTH administration. After infusion of the hormone, HCO3 excretion increased significantly but the U-B PCO2 gradient remained unchanged. The effects of PTH infusion on urinary acidification in animals with distal renal tubular acidosis caused by LiCl administration were also studied. PTH administration to these dogs increased HCO3 excretion to the same level seen in normal dogs. These data suggest that PTH does not inhibit distal H+ secretion but increases HCO3 excretion by depressing proximal HCO3 reabsorption. | Effect of parathyroid hormone on urinary acidification. The effect of parathyroid hormone (PTH) administration on urinary acidification was studied in intact and thyroparathyroidectomized dogs. PTH administration resulted in a significant increase in urine pH and HCO3 excretion. In dogs with maximally acid urine caused by Na2SO4 infusion PTH administration also led to a significant increase in urine pH and to a decrease in ammonium excretion. To examine the effect of PTH on H+ secretion in the distal nephron we measured the urine-blood (U-B) PCO2 gradient in dogs with maximally alkaline urine (urine pH greater than 7.8) before and after PTH administration. After infusion of the hormone, HCO3 excretion increased significantly but the U-B PCO2 gradient remained unchanged. The effects of PTH infusion on urinary acidification in animals with distal renal tubular acidosis caused by LiCl administration were also studied. PTH administration to these dogs increased HCO3 excretion to the same level seen in normal dogs. These data suggest that PTH does not inhibit distal H+ secretion but increases HCO3 excretion by depressing proximal HCO3 reabsorption. | [
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PMID:16501 | Distribution of adenine nucleotides in the perfused rat heart. | A computer technique for determination of the distribution of adenine nucleotides among compartmented, protonated, and metal-chelated species has been developed for the perfused rat heart. This procedure requires knowledge of tissue levels of creatine, creatine phosphate, ATP, ADP, and AMP and the glycolytic and respiration rates. The method is applicable to any physiological state of the organ and has been applied to transient behavior in aerobic, anoxic, and ischemic hearts. The results suggest that ADP uptake and ATP export by mitochondria are normally linked and equal in rate during aerobic metabolism or short-term anoxia but become separate and unequal during ischemia, so that mitochondrial adenine nucleotides, primarily AMP, accumulate. | Distribution of adenine nucleotides in the perfused rat heart. A computer technique for determination of the distribution of adenine nucleotides among compartmented, protonated, and metal-chelated species has been developed for the perfused rat heart. This procedure requires knowledge of tissue levels of creatine, creatine phosphate, ATP, ADP, and AMP and the glycolytic and respiration rates. The method is applicable to any physiological state of the organ and has been applied to transient behavior in aerobic, anoxic, and ischemic hearts. The results suggest that ADP uptake and ATP export by mitochondria are normally linked and equal in rate during aerobic metabolism or short-term anoxia but become separate and unequal during ischemia, so that mitochondrial adenine nucleotides, primarily AMP, accumulate. | [
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PMID:16502 | Computer simulation of energy metabolism in anoxic perfused rat heart. | We have modeled the energy metabolism of the perfused rat heart in order to elucidate the interaction of physiological and biochemical control mechanisms. This model which includes glycolysis, the Krebs cycle, and related metabolism, contains 68 submodels of individual enzymes and transport mechanisms including both cytosolic and mitochondrial reactions. The method of model construction, which relies heavily on fitting observed in situ behavior to known algebraic rate laws for isolated enzymes, and its data requirements and necessary assumptions are described. Simulation of a CO-induced anoxic preparation is described in detail. Here glycolysis increases sharply, due to both increased glucose uptake and phosphorylase activation (there is rapid interconversion between a and b forms, both of which are active here); this causes a damped glycolytic oscillation originating with the glycogen-handling enzymes rather than phosphofructokinase. The behavior and physiological consequences of ATPase activity and of a lactate permease which exports lactate to the perfusate are discussed. | Computer simulation of energy metabolism in anoxic perfused rat heart. We have modeled the energy metabolism of the perfused rat heart in order to elucidate the interaction of physiological and biochemical control mechanisms. This model which includes glycolysis, the Krebs cycle, and related metabolism, contains 68 submodels of individual enzymes and transport mechanisms including both cytosolic and mitochondrial reactions. The method of model construction, which relies heavily on fitting observed in situ behavior to known algebraic rate laws for isolated enzymes, and its data requirements and necessary assumptions are described. Simulation of a CO-induced anoxic preparation is described in detail. Here glycolysis increases sharply, due to both increased glucose uptake and phosphorylase activation (there is rapid interconversion between a and b forms, both of which are active here); this causes a damped glycolytic oscillation originating with the glycogen-handling enzymes rather than phosphofructokinase. The behavior and physiological consequences of ATPase activity and of a lactate permease which exports lactate to the perfusate are discussed. | [
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PMID:16503 | Computer simulation of rat heart metabolism after adding glucose to the perfusate. | An experiment where perfused rat hearts receiving no substrate are suddenly given glucose with insulin in the perfusate is simulated with a computer model of cardiac energy metabolism. Mitochondrial metabolism is quantitatively reorganized under cytoplasmic control, with fatty acid oxidation undergoing a two-step decrease. There is an unspanning of the Krebs cycle (different reactions going at different rates) due primarily to slowing of alpha-ketoglutarate dehydrogenase; this ends when cytoplasmic glucose reaches a new steady state. Mitochondria in vitro are known to have higher pH than their surroundings; it is found here that this also holds in situ. Under these conditions, glycolysis is coherently substrate controlled, as is phosphofructokinase, usually considered the typical example of an allosteric enzyme. Limitations on simple methods of analyzing metabolic data of this type, e.g., use of lactate/pyruvate ratios to calculate NADH/NAD ratios, are discussed. Here a large volume of enzyme and other biochemical information has been integrated into a physiologically meaningful system. | Computer simulation of rat heart metabolism after adding glucose to the perfusate. An experiment where perfused rat hearts receiving no substrate are suddenly given glucose with insulin in the perfusate is simulated with a computer model of cardiac energy metabolism. Mitochondrial metabolism is quantitatively reorganized under cytoplasmic control, with fatty acid oxidation undergoing a two-step decrease. There is an unspanning of the Krebs cycle (different reactions going at different rates) due primarily to slowing of alpha-ketoglutarate dehydrogenase; this ends when cytoplasmic glucose reaches a new steady state. Mitochondria in vitro are known to have higher pH than their surroundings; it is found here that this also holds in situ. Under these conditions, glycolysis is coherently substrate controlled, as is phosphofructokinase, usually considered the typical example of an allosteric enzyme. Limitations on simple methods of analyzing metabolic data of this type, e.g., use of lactate/pyruvate ratios to calculate NADH/NAD ratios, are discussed. Here a large volume of enzyme and other biochemical information has been integrated into a physiologically meaningful system. | [
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PMID:16504 | Relationship between gastric mucosal pH and site of peptic ulceration. | Measurements of mucosal pH of resected stomachs were carried out in gastric and duodenal ulcer patients. Low mucosal pH along the lesser curvature and relatively higher gastric pepsin levels were found. It is suggested that this lower pH affects gastric ulcer occurrence in the limited "lesser curvature area" where 63 per cent of the ulcers were situated. It is also suggested that increased pepsin activity present in gastric ulcer patients may be another factor affecting gastric ulcer formation by virtue of pepsins activated at higher pH. In duodenal ulcer patients, these factors are "overshadowed" by high acid-pepsin secretory activity of gastric juice. | Relationship between gastric mucosal pH and site of peptic ulceration. Measurements of mucosal pH of resected stomachs were carried out in gastric and duodenal ulcer patients. Low mucosal pH along the lesser curvature and relatively higher gastric pepsin levels were found. It is suggested that this lower pH affects gastric ulcer occurrence in the limited "lesser curvature area" where 63 per cent of the ulcers were situated. It is also suggested that increased pepsin activity present in gastric ulcer patients may be another factor affecting gastric ulcer formation by virtue of pepsins activated at higher pH. In duodenal ulcer patients, these factors are "overshadowed" by high acid-pepsin secretory activity of gastric juice. | [
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PMID:16506 | The role of analgesics in respiratory depression: a rabbit model. | The study of the effect of analgesics in the newborn is difficult in the clinical situation and resort must be made to animals. Pethidine given within 1 hour of delivery is believed to cause less depression than when the time interval is longer. This study investigates whether it is pethidine or its metabolites which cause respiratory depression by comparing the respiratory effects of pethidine and its metabolites in the newborn rabbit. Fentanyl and buphrenorphine were also investigated as alternative analgesics. The response in the newborn rabbit to anoxia, is periods of dyspnoea, primary apnoea, and gasping. The metabolites of pethidine increased the primary apnoea signifying depression almost as much as pethidine. Depression was also produced when anoxia was induced 5 minutes after pethidine. Fentanyl caused less depression than pethidine or its metabolites excepting normeperidinic acid. Buphrenorphine administration resulted in the least depression with little difference between the low and high doses. Thus both pethidine and its metabolites are factors in the persisting depression, while buphrenorphine compared well with pethidine and fentanyl. | The role of analgesics in respiratory depression: a rabbit model. The study of the effect of analgesics in the newborn is difficult in the clinical situation and resort must be made to animals. Pethidine given within 1 hour of delivery is believed to cause less depression than when the time interval is longer. This study investigates whether it is pethidine or its metabolites which cause respiratory depression by comparing the respiratory effects of pethidine and its metabolites in the newborn rabbit. Fentanyl and buphrenorphine were also investigated as alternative analgesics. The response in the newborn rabbit to anoxia, is periods of dyspnoea, primary apnoea, and gasping. The metabolites of pethidine increased the primary apnoea signifying depression almost as much as pethidine. Depression was also produced when anoxia was induced 5 minutes after pethidine. Fentanyl caused less depression than pethidine or its metabolites excepting normeperidinic acid. Buphrenorphine administration resulted in the least depression with little difference between the low and high doses. Thus both pethidine and its metabolites are factors in the persisting depression, while buphrenorphine compared well with pethidine and fentanyl. | [
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|
PMID:16507 | Formaldehyde formation as a metabolite of methoxyflurane. | The production of formaldehyde as a metabolite of enzymatic biotransformation of methoxyflurane was observed in vitro in hepatic microsomal preparations derived from Japanese monkeys, rabbits and Wistar strain rats. Production rates of formaldehyde were 0.80-2.50 n moles/mg protein/min in the induced group which was pretreated with phenobarbitone, and 0.15-0.68 n moles/mg protein/min in the non-induced group. This reaction needed the presence of NADPH and oxygen. Formaldehyde production was almost completely inhibited by addition of 25% CO. Further degradation of formaldehyde did not occur in microsomal suspension. No detectable species difference was observed among the animals used in this study. These results indicate that the biotransformation of methoxyflurane is preceded by interaction with cytochrome p-450 in hepatic microsomes in the presence of NADPH and oxygen. | Formaldehyde formation as a metabolite of methoxyflurane. The production of formaldehyde as a metabolite of enzymatic biotransformation of methoxyflurane was observed in vitro in hepatic microsomal preparations derived from Japanese monkeys, rabbits and Wistar strain rats. Production rates of formaldehyde were 0.80-2.50 n moles/mg protein/min in the induced group which was pretreated with phenobarbitone, and 0.15-0.68 n moles/mg protein/min in the non-induced group. This reaction needed the presence of NADPH and oxygen. Formaldehyde production was almost completely inhibited by addition of 25% CO. Further degradation of formaldehyde did not occur in microsomal suspension. No detectable species difference was observed among the animals used in this study. These results indicate that the biotransformation of methoxyflurane is preceded by interaction with cytochrome p-450 in hepatic microsomes in the presence of NADPH and oxygen. | [
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PMID:16508 | [Anaesthesia with flunitrazepam (rohypnol) and fentanyl for geriatric patients (author's transl)]. | Favorable clinic experiences with an anaesthetic involving rohypnol (flunitrazepam) and fentanyl led to an investigation of the haemodynamic effect of this procedure in a group of 9 geriatric patients, aged from 86 to 95 years. Anaesthesia was induced with 0.5 mg rohypnol and 0.1 to 0.2 mg fentanyl depending on the narcotic effect of rohypnol, intubation was performed under relaxation with suxamethonium and long term relaxation was achieved with pancuronium. The patients were normoventilated with nitrous oxide/oxygen. The individual values of the changes in cardiac output and total peripheral resistance showed a great variation. There was a significant correlation between the relative changes in mean arterial pressure and total peripheral resistance (r = 0.69, p less than 0.05) but no correlation between mean arterial pressure and cardiac output (r = 0.09). This indicates that the pronounced drop in arterial pressure which occurred in 4 patients can be explained by a decrease in total peripheral resistance. Careful dosage of the drugs, in particular of fentanyl, and knowledge of adequate measures to treat a decrease in blood pressure if it occurs, appears to be a prerequisite for the use of this type of anaesthesia in poor risk patients. | [Anaesthesia with flunitrazepam (rohypnol) and fentanyl for geriatric patients (author's transl)]. Favorable clinic experiences with an anaesthetic involving rohypnol (flunitrazepam) and fentanyl led to an investigation of the haemodynamic effect of this procedure in a group of 9 geriatric patients, aged from 86 to 95 years. Anaesthesia was induced with 0.5 mg rohypnol and 0.1 to 0.2 mg fentanyl depending on the narcotic effect of rohypnol, intubation was performed under relaxation with suxamethonium and long term relaxation was achieved with pancuronium. The patients were normoventilated with nitrous oxide/oxygen. The individual values of the changes in cardiac output and total peripheral resistance showed a great variation. There was a significant correlation between the relative changes in mean arterial pressure and total peripheral resistance (r = 0.69, p less than 0.05) but no correlation between mean arterial pressure and cardiac output (r = 0.09). This indicates that the pronounced drop in arterial pressure which occurred in 4 patients can be explained by a decrease in total peripheral resistance. Careful dosage of the drugs, in particular of fentanyl, and knowledge of adequate measures to treat a decrease in blood pressure if it occurs, appears to be a prerequisite for the use of this type of anaesthesia in poor risk patients. | [
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PMID:16509 | [Paresis of the tympanic nerve--a rare complication of spinal anesthesia (author's transl)]. | Acut impairment of hearing following spinal anaesthesia is described. The cause, treatment of and incidence rate of neurological complications of spinal anaesthesia are discussed. | [Paresis of the tympanic nerve--a rare complication of spinal anesthesia (author's transl)]. Acut impairment of hearing following spinal anaesthesia is described. The cause, treatment of and incidence rate of neurological complications of spinal anaesthesia are discussed. | [
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|
PMID:16512 | Alpha-adrenergic blocking action of fentanyl on the isolated aorta of the rabbit. | The contractile response of helically-cut strips of rabbit ascending aorta to transmural electrical stimulation was attenuated in a dose-dependent manner by treatment for 20 min with fentanyl, 10(-6) to 10(-5) M. Fentanyl also shifted the dose-response curve of the contractile response of aorta to norepinephrine to the right. The response to transmural stimulation was more resistant to fentanyl than was the response to an equipotent dose of norepinephrine. The inhibitory effect of fentanyl was neither prevented nor reversed by naloxone, but was partially reversed by repeated washing of the preparations. The contractile responses to histamine and serotonin were not significantly altered by fentanyl. Treatment with fentanyl as well as phentolamine protected alpha-adrenergic receptors from persistent blockade by phenoxybenzamine. Morphine to 10(-3) M failed to influence the dose-response curve of norepinephrine significantly. It may be concluded that fentanyl reversibly blocks alpha-adrenergic receptors in a competitive manner in vascular smooth muscle, and the potency of fentanyl is approximately 1/30 that of phentolamine. | Alpha-adrenergic blocking action of fentanyl on the isolated aorta of the rabbit. The contractile response of helically-cut strips of rabbit ascending aorta to transmural electrical stimulation was attenuated in a dose-dependent manner by treatment for 20 min with fentanyl, 10(-6) to 10(-5) M. Fentanyl also shifted the dose-response curve of the contractile response of aorta to norepinephrine to the right. The response to transmural stimulation was more resistant to fentanyl than was the response to an equipotent dose of norepinephrine. The inhibitory effect of fentanyl was neither prevented nor reversed by naloxone, but was partially reversed by repeated washing of the preparations. The contractile responses to histamine and serotonin were not significantly altered by fentanyl. Treatment with fentanyl as well as phentolamine protected alpha-adrenergic receptors from persistent blockade by phenoxybenzamine. Morphine to 10(-3) M failed to influence the dose-response curve of norepinephrine significantly. It may be concluded that fentanyl reversibly blocks alpha-adrenergic receptors in a competitive manner in vascular smooth muscle, and the potency of fentanyl is approximately 1/30 that of phentolamine. | [
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|
PMID:16511 | The splitting of sperm heads from tails in eight mammalian species and the measurement of their sizes. | Ejaculated spermatozoa from man, the Euopean wild boar and the bull, and spermatozoa from the cauda epididymes of the rabbit, rat, mouse, hamster and Guinea pig were treated with a sonic bath, a sonic probe, trypsin with and without prior treatment with a sulphhydryl reagent, pronase and alkalis. The fragments produced were counted and sized in an accurately calibrated Coulter Counter, Model ZB Industrial, before and after Zaponin treatment to lyse accompanying debris and the peripheral cytoplasm. Head and tail fractions were separated on sucrose gradients. Each species required different conditions for cleavage or fragmentation. Rabbit and bull spermatozoa were cleaved by the ultrasonic bath exactly into heads and tails, producing twice the number of particles with two peaks in the size distribution curves butith some 60% loss of total sperm volume which became the soluble fraction. The ultrasonic probe, and for the bull, pronase, produced the same cleavage but these more drastic treatments dissolved a considerable portion of the tail fraction. Rodent spermatozoa, especially the rat, were cleaved perfectly into heads and tails by mild trypsin treatment. All the nonrodent spermatozoa were resistent to trypsin cleavage, although prior treatment with a sulphhydryl reagent caused swelling and subsequent trypsin action caused digestion into miscellaneous pieces. Spermatozoa from the boar and from man could not be cleaved by any of the procedures. The sonic probe produced fragmentation with progressive dissolution of the tail fragments and a single peak in the size distribution curve corresponding to small stripped heads. The soluble fraction always constituted a large proportion of the original whole spermatozoa. | The splitting of sperm heads from tails in eight mammalian species and the measurement of their sizes. Ejaculated spermatozoa from man, the Euopean wild boar and the bull, and spermatozoa from the cauda epididymes of the rabbit, rat, mouse, hamster and Guinea pig were treated with a sonic bath, a sonic probe, trypsin with and without prior treatment with a sulphhydryl reagent, pronase and alkalis. The fragments produced were counted and sized in an accurately calibrated Coulter Counter, Model ZB Industrial, before and after Zaponin treatment to lyse accompanying debris and the peripheral cytoplasm. Head and tail fractions were separated on sucrose gradients. Each species required different conditions for cleavage or fragmentation. Rabbit and bull spermatozoa were cleaved by the ultrasonic bath exactly into heads and tails, producing twice the number of particles with two peaks in the size distribution curves butith some 60% loss of total sperm volume which became the soluble fraction. The ultrasonic probe, and for the bull, pronase, produced the same cleavage but these more drastic treatments dissolved a considerable portion of the tail fraction. Rodent spermatozoa, especially the rat, were cleaved perfectly into heads and tails by mild trypsin treatment. All the nonrodent spermatozoa were resistent to trypsin cleavage, although prior treatment with a sulphhydryl reagent caused swelling and subsequent trypsin action caused digestion into miscellaneous pieces. Spermatozoa from the boar and from man could not be cleaved by any of the procedures. The sonic probe produced fragmentation with progressive dissolution of the tail fragments and a single peak in the size distribution curve corresponding to small stripped heads. The soluble fraction always constituted a large proportion of the original whole spermatozoa. | [
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|
PMID:16518 | [Membrane oxygenators in cardiac surgery: progress]. | This study tries to define if the membrane oxygenators are available during cardiac surgery under E.C.C., and if their performance are superior to those of conventional oxygenators. Two series of research are done. In the first one, we compare performance of two membrane oxygenators: the Rhône-Poulenc heart-lung machine (10 cases) and the Travenol TMO Teflo machine (100 cases). The general impression is good: the two proposed systems seem to be perfectly well adapted to surgical utilization conditions, avoiding excessive ventilations and eventually allowing to keep on E.C.C. in postoperative. In the second part of this work, two series of patients are studied, one oeprated under membrane oxygenator (Teflo), the second under bubble oxygenator (Bentley Q 100). Comparative study shows small differences between the two groups. Only the post-operative enzymatic profile is clearly for the membrane oxygenator which also insure a waking and a postoperative recovery of highest quality. These first observations justify to keep on using of membrane oxygenators in cardiac surgery. | [Membrane oxygenators in cardiac surgery: progress]. This study tries to define if the membrane oxygenators are available during cardiac surgery under E.C.C., and if their performance are superior to those of conventional oxygenators. Two series of research are done. In the first one, we compare performance of two membrane oxygenators: the Rhône-Poulenc heart-lung machine (10 cases) and the Travenol TMO Teflo machine (100 cases). The general impression is good: the two proposed systems seem to be perfectly well adapted to surgical utilization conditions, avoiding excessive ventilations and eventually allowing to keep on E.C.C. in postoperative. In the second part of this work, two series of patients are studied, one oeprated under membrane oxygenator (Teflo), the second under bubble oxygenator (Bentley Q 100). Comparative study shows small differences between the two groups. Only the post-operative enzymatic profile is clearly for the membrane oxygenator which also insure a waking and a postoperative recovery of highest quality. These first observations justify to keep on using of membrane oxygenators in cardiac surgery. | [
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|
PMID:16519 | [Methods of sampling and preservation of blood used during extracorporeal circulation]. | The blood supply of Cardiac Surgery Centers set quantitative and qualitative problems to the Centers of blood dispatch. In this work, from a Lyonese experience on 4,000 E.C.C., authors try to define the best preservative solution, especially for the respiratory function of the red blood cell. The C.P.D. solution (citrate, phosphate, dextrose) answers to requirements in this field when the blood used is less than 48 hours old. In the meantime, it is not impossible that studies based on definite criteriums of evaluation and on severe comparisons allows to adapt new process from which some are described and criticized in this work. | [Methods of sampling and preservation of blood used during extracorporeal circulation]. The blood supply of Cardiac Surgery Centers set quantitative and qualitative problems to the Centers of blood dispatch. In this work, from a Lyonese experience on 4,000 E.C.C., authors try to define the best preservative solution, especially for the respiratory function of the red blood cell. The C.P.D. solution (citrate, phosphate, dextrose) answers to requirements in this field when the blood used is less than 48 hours old. In the meantime, it is not impossible that studies based on definite criteriums of evaluation and on severe comparisons allows to adapt new process from which some are described and criticized in this work. | [
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|
PMID:16520 | [Value of using cell concentrates, preserved by freezing, during extracorporeal circulation]. | The effectiveness of transfusions of frozen red cells has presently been clearly demonstrated. The authors present their technique of preparation of these cells and their experience of this material in 51 cases of ECC. The results observed plead in favour of the notion that frozen-defrosted blood, combines the advantages of washed blood, freed from all plasma and cellular contaminants of fresh blood with preservation of the oxyphoric power. Going beyond the realm of ECC, the authors think that cryopreservation of blood should be applied to the majority of indications for transfusions. | [Value of using cell concentrates, preserved by freezing, during extracorporeal circulation]. The effectiveness of transfusions of frozen red cells has presently been clearly demonstrated. The authors present their technique of preparation of these cells and their experience of this material in 51 cases of ECC. The results observed plead in favour of the notion that frozen-defrosted blood, combines the advantages of washed blood, freed from all plasma and cellular contaminants of fresh blood with preservation of the oxyphoric power. Going beyond the realm of ECC, the authors think that cryopreservation of blood should be applied to the majority of indications for transfusions. | [
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PMID:16521 | [Technics, value and limitations of hemodilution in extracorporeal circulation]. | Hemodilution during E.C.C. is into use for more than 15 years. Its interest is obvious (blood economy, beneficient action on viscosity, prevention of "sludging"), but opinions are different concerning the best level of hemodiultion. The authors defend the notion of a moderate dilution (hematocrit larger than or equal to 25 p. 100) required to maintain a high perfusion pressure. For atherosclerotic patients, they describe the hemodilution technics tried on more than 4,000 cases since 1964. The advantages of hemodilution concern on one hand the diminution or the disparition of drawbacks and complications due to the obtainment and to the administration of homologous blood and on the other hand the beneficient intrinsical effects of the blood dilution on the tissular perfusion. In convenients are those due to changes in the concentration of sodium, chlore and specially potassium which may be responsible of serious cardiac arrythmias. Because of increasing difficulties concerning the use of homologous blood (obtaining difficulties and complications relative to its use), the authors consider the utilization of autologous blood taken off before the operation on the patient and freezed. | [Technics, value and limitations of hemodilution in extracorporeal circulation]. Hemodilution during E.C.C. is into use for more than 15 years. Its interest is obvious (blood economy, beneficient action on viscosity, prevention of "sludging"), but opinions are different concerning the best level of hemodiultion. The authors defend the notion of a moderate dilution (hematocrit larger than or equal to 25 p. 100) required to maintain a high perfusion pressure. For atherosclerotic patients, they describe the hemodilution technics tried on more than 4,000 cases since 1964. The advantages of hemodilution concern on one hand the diminution or the disparition of drawbacks and complications due to the obtainment and to the administration of homologous blood and on the other hand the beneficient intrinsical effects of the blood dilution on the tissular perfusion. In convenients are those due to changes in the concentration of sodium, chlore and specially potassium which may be responsible of serious cardiac arrythmias. Because of increasing difficulties concerning the use of homologous blood (obtaining difficulties and complications relative to its use), the authors consider the utilization of autologous blood taken off before the operation on the patient and freezed. | [
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|
PMID:16522 | [Biological aspects of extracorporeal circulation]. | Two problems are looked at in this work. That of glucose which is administered in considerable quantities during ECC and that of the iso-enzymes. The administration of glucose has two aims: one being the mechanical nature i.e. as an agent which decreases the risks of platelet aggregation, the other bio-energetic. But, owing to the CRABTREEE effect, an excess of glucose blocks the biosynthesis of ATP and a non-metabolisable structural analogue which has mechanical properties identical with glucose, such as fucose or rhamnose could be supplied instead. As far as the iso-enzymes are concerned, the author after having looked at the general value from the standpoint of signs and symptoms, suggests the study of two of them, cardiac lactic-dehydrogenase and the MB fraction of creatine phosphokinase could enable the follow-up of the course and of the consequences of extra-corporeal circulation. | [Biological aspects of extracorporeal circulation]. Two problems are looked at in this work. That of glucose which is administered in considerable quantities during ECC and that of the iso-enzymes. The administration of glucose has two aims: one being the mechanical nature i.e. as an agent which decreases the risks of platelet aggregation, the other bio-energetic. But, owing to the CRABTREEE effect, an excess of glucose blocks the biosynthesis of ATP and a non-metabolisable structural analogue which has mechanical properties identical with glucose, such as fucose or rhamnose could be supplied instead. As far as the iso-enzymes are concerned, the author after having looked at the general value from the standpoint of signs and symptoms, suggests the study of two of them, cardiac lactic-dehydrogenase and the MB fraction of creatine phosphokinase could enable the follow-up of the course and of the consequences of extra-corporeal circulation. | [
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|
PMID:16523 | [Sodium supply in operations under extracorporeal circulation in children]. | In order to explain the edematous appearance found in infants after ECC associated with hyponatremia, the authors studied the supply of sodium per and post-operatively in 42 children aged from 11 days to 13 years undergoing correction of the cardiopathy under ECC. This study enables one to find that there is an inflation of sodium after intervention under ECC, which is even more important, the longer the duration of the ECC. It is not related to a failure in urinary excretion of Na+ and predominates in infants. It is related with the supply of sodium during transfusion and seems to be the cause of certain respiratory complications met with following ECC. | [Sodium supply in operations under extracorporeal circulation in children]. In order to explain the edematous appearance found in infants after ECC associated with hyponatremia, the authors studied the supply of sodium per and post-operatively in 42 children aged from 11 days to 13 years undergoing correction of the cardiopathy under ECC. This study enables one to find that there is an inflation of sodium after intervention under ECC, which is even more important, the longer the duration of the ECC. It is not related to a failure in urinary excretion of Na+ and predominates in infants. It is related with the supply of sodium during transfusion and seems to be the cause of certain respiratory complications met with following ECC. | [
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PMID:16525 | [Hemodynamic parameters which should be watched during and immediately after extracorporeal circulation]. | The author studies only the usual investigations required for watching E.C.C. during the operatory period and directly afterwards. During E.C.C., one must essentially oversee the flow (2,4l/m2 or 70 ml/kg), the arterial pressure (70 torrs) essential factor for myocardiac injection, the C.V.P., where excess is factor of cerebral oedema, the peripheric vascular resistances (P.V.R.) which inform on the level of vasomotoricity. Control of pulmonary capillary pressure (P.C.P.), which is under E.C.C. the reflection of the left ventricular pressure (L.V.P.) is also a capital element of this watching (any elevation of L.V.P. is factor of sub-endocardiac ischemia and of acute pulmonary edema). In post E.C.C., the same parameters will be watched. A cardiac output equal or inferior to 2 l/m2 involve an immediate treatment. The C.V.P. allows adaptation of blood quantity. Calcul of V.P.R. sets treatment of low cardiac output. C.P.C. control allows evaluation of left ventricular efficacity. These datas must be completed by calcul of subendocardiac viability by studying the arterial pressure curves which inform on oxygen supply and demand, and by the contractility index measure (aortic output speed and measure of systolic interval). | [Hemodynamic parameters which should be watched during and immediately after extracorporeal circulation]. The author studies only the usual investigations required for watching E.C.C. during the operatory period and directly afterwards. During E.C.C., one must essentially oversee the flow (2,4l/m2 or 70 ml/kg), the arterial pressure (70 torrs) essential factor for myocardiac injection, the C.V.P., where excess is factor of cerebral oedema, the peripheric vascular resistances (P.V.R.) which inform on the level of vasomotoricity. Control of pulmonary capillary pressure (P.C.P.), which is under E.C.C. the reflection of the left ventricular pressure (L.V.P.) is also a capital element of this watching (any elevation of L.V.P. is factor of sub-endocardiac ischemia and of acute pulmonary edema). In post E.C.C., the same parameters will be watched. A cardiac output equal or inferior to 2 l/m2 involve an immediate treatment. The C.V.P. allows adaptation of blood quantity. Calcul of V.P.R. sets treatment of low cardiac output. C.P.C. control allows evaluation of left ventricular efficacity. These datas must be completed by calcul of subendocardiac viability by studying the arterial pressure curves which inform on oxygen supply and demand, and by the contractility index measure (aortic output speed and measure of systolic interval). | [
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|
PMID:16526 | [Protection of the myocardium by hypothermia during extracorporeal circulation. Experimental and clinical study]. | Hypothermic protection of myocardia during E.C.C. has been estimated on a 35 dogs experimental series and on a clinical series of 700 acquired cardiopathies of adult, including 400 valvular replacements and 300 aorto-coronary by-pass. Experimental results have been estimated by biochemic and morphologic controls done on myocardic samples took up by drillbiopsy. The biochemical study includes among others a dosing of the high-energy phosphorus compounds (P.C. and A.T.P.). Morphological study was done by optic and electronic microscopy. Results made clear the superiority of the hypothermic ischemia at 10 degrees C on the continued perfusion at 32 degrees C with fibrillative heart. An hypothermic protection method with successively cold perfusion of the coronary system and a heart immersion in a salted solution at 4 degrees C has been utilized during valvular and coronary surgery on human in 700 cases. The total mortality was of 5,8 p. 100. The rate of post-operative infarcts was 2,4 p. 100. Incidence of intra-ventricular conduction troubles has been 1,1 p. 100. There was no relation between mortality and morbidity of myocardic origin and the lasting of the ischemic clamp, which were of 21 mn up to 165 mn. The low incidence of complications of myocardic origin is due to the hypothermic protection of the myocardia. | [Protection of the myocardium by hypothermia during extracorporeal circulation. Experimental and clinical study]. Hypothermic protection of myocardia during E.C.C. has been estimated on a 35 dogs experimental series and on a clinical series of 700 acquired cardiopathies of adult, including 400 valvular replacements and 300 aorto-coronary by-pass. Experimental results have been estimated by biochemic and morphologic controls done on myocardic samples took up by drillbiopsy. The biochemical study includes among others a dosing of the high-energy phosphorus compounds (P.C. and A.T.P.). Morphological study was done by optic and electronic microscopy. Results made clear the superiority of the hypothermic ischemia at 10 degrees C on the continued perfusion at 32 degrees C with fibrillative heart. An hypothermic protection method with successively cold perfusion of the coronary system and a heart immersion in a salted solution at 4 degrees C has been utilized during valvular and coronary surgery on human in 700 cases. The total mortality was of 5,8 p. 100. The rate of post-operative infarcts was 2,4 p. 100. Incidence of intra-ventricular conduction troubles has been 1,1 p. 100. There was no relation between mortality and morbidity of myocardic origin and the lasting of the ischemic clamp, which were of 21 mn up to 165 mn. The low incidence of complications of myocardic origin is due to the hypothermic protection of the myocardia. | [
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|
PMID:16527 | [Myocardial protection by coronary perfusion and specific problems of myocardial protection in combined valvular and coronary surgery]. | The quality of the myocardial protection by bilateral coronary perfusion was studied in a consecutive series of 80 patients treated by isolated aortic replacements (47 cases) or multiple replacements (mitro-aortic, or mitro-aortic and tricuspid) 33 cases. Four low outputs (5 p. 100) were observed with only one death. Five post-operative necroses (6.25) were noted. The overall surgical mortality was 6.25 p. 100 (5 cases out of 80). There were two deaths in the series of the 47 single replacements and three deaths (9) in the series of multiple replacements. At the same time, the myocardial protection was studied in a consecutive series of 12 cases of valvular replacements combined with coronary shunts. In all of the cases, the shunt or shunts were carried out first, the myocardial protection was subsequently ensured by a coronary perfusion carried out by means of the shunts and directly through the coronary orifices. There were 2 deaths (16), 2 necroses (16) both responsible for deaths and no low output in the 10 survivors. Coronary perfusion very certainly ensures an excellent quality of myocardial protection if certain criteria are respected: hypothermia, moderate (28 degrees) bilateral perfusion with a mean perfusion pressure above 100 also ensuring a good flow through the sub-endocardial layer, which remains particularly sensitive to ischiemia. In cases of associated shunts, they must be carried out, first of all, in cases of tight senoses, over 60. | [Myocardial protection by coronary perfusion and specific problems of myocardial protection in combined valvular and coronary surgery]. The quality of the myocardial protection by bilateral coronary perfusion was studied in a consecutive series of 80 patients treated by isolated aortic replacements (47 cases) or multiple replacements (mitro-aortic, or mitro-aortic and tricuspid) 33 cases. Four low outputs (5 p. 100) were observed with only one death. Five post-operative necroses (6.25) were noted. The overall surgical mortality was 6.25 p. 100 (5 cases out of 80). There were two deaths in the series of the 47 single replacements and three deaths (9) in the series of multiple replacements. At the same time, the myocardial protection was studied in a consecutive series of 12 cases of valvular replacements combined with coronary shunts. In all of the cases, the shunt or shunts were carried out first, the myocardial protection was subsequently ensured by a coronary perfusion carried out by means of the shunts and directly through the coronary orifices. There were 2 deaths (16), 2 necroses (16) both responsible for deaths and no low output in the 10 survivors. Coronary perfusion very certainly ensures an excellent quality of myocardial protection if certain criteria are respected: hypothermia, moderate (28 degrees) bilateral perfusion with a mean perfusion pressure above 100 also ensuring a good flow through the sub-endocardial layer, which remains particularly sensitive to ischiemia. In cases of associated shunts, they must be carried out, first of all, in cases of tight senoses, over 60. | [
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|
PMID:16528 | [Computer analysis of a method of myocardial protection used in a series of 547 operations under extracorporeal circulation in adults]. | During 4 years (1970-1974), the numerous pre, per and post-operative datas collected for each adult operated under E.C.C. by the same surgeon, have been analysed on computer (547 cases). The myocardic protection method was unvariable: steady hypothermia of 30 degrees C, induced ventricular fibrillation, myocardic anoxia time less than 15 mn, strict out-bubbles of the left cavities. A direct perfusion of the coronary arteries has been used in case of aortotomy. Analysis of the early post-operative mortality causes and of the various post-operative myocardic complications did not reveal any baneful influence of this myocardic protection method. The average post-operative left auricular pressure, the most reliable test of the left ventricular dynamics, or its post-operative variations are independent of the ventricular fibrillation time, the perfusion time or the coronal output used. | [Computer analysis of a method of myocardial protection used in a series of 547 operations under extracorporeal circulation in adults]. During 4 years (1970-1974), the numerous pre, per and post-operative datas collected for each adult operated under E.C.C. by the same surgeon, have been analysed on computer (547 cases). The myocardic protection method was unvariable: steady hypothermia of 30 degrees C, induced ventricular fibrillation, myocardic anoxia time less than 15 mn, strict out-bubbles of the left cavities. A direct perfusion of the coronary arteries has been used in case of aortotomy. Analysis of the early post-operative mortality causes and of the various post-operative myocardic complications did not reveal any baneful influence of this myocardic protection method. The average post-operative left auricular pressure, the most reliable test of the left ventricular dynamics, or its post-operative variations are independent of the ventricular fibrillation time, the perfusion time or the coronal output used. | [
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|
PMID:16529 | [Changes in myocardial tolerance to ischemia as a function of circulatory arrest mechanisms]. | This study tries to specify the tolerance limit of heart to ischemia and has three parts. In the first one, the author considers the heart resistance in normothermy related to the circulatory arrest type, the anesthetic technique, existence or not or a ventricular fibrillation. Everybody is tody in agreement to admit that 35 to 45 minutes are the security limit of the cardiogenous circulatory stop. In the second part, conditions of cardiac tolerance to ischemia in hypothermy are foreseen. The security margin is here large, provided a nonagressive realization of the cooling. Lastly, the author reports the looseness of the biochimic, histochemic or histologic criteriums which permit an appreciation of the heart functional capacity, appreciation which still persist to be essentially clinical. | [Changes in myocardial tolerance to ischemia as a function of circulatory arrest mechanisms]. This study tries to specify the tolerance limit of heart to ischemia and has three parts. In the first one, the author considers the heart resistance in normothermy related to the circulatory arrest type, the anesthetic technique, existence or not or a ventricular fibrillation. Everybody is tody in agreement to admit that 35 to 45 minutes are the security limit of the cardiogenous circulatory stop. In the second part, conditions of cardiac tolerance to ischemia in hypothermy are foreseen. The security margin is here large, provided a nonagressive realization of the cooling. Lastly, the author reports the looseness of the biochimic, histochemic or histologic criteriums which permit an appreciation of the heart functional capacity, appreciation which still persist to be essentially clinical. | [
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|
PMID:16530 | [Neuroplegia and extracorporeal circulation. Comparison between combinations of droperidol-phenoperidine and chlorprothixene-dextromoramide in cardiac surgery]. | After a quick review of the physiopathology of extra-corporeal circulation, the value of the use of neuroplegic drugs in cardiac surgery is recalled by means of pharmacological arguments. The experimental differences existing between the combinations droperidol - phenoperidine and chlorportixene - dextromoramide, on the rate of flow and on the pressure of the perfusion, and on the esophago-rectal thermic gradients during E.C.C. is then demonstrated. Statistic calculation confirmed the superiority of chlorprotixene in the realm of tissue perfusion during E.C.C. under hypothermia. | [Neuroplegia and extracorporeal circulation. Comparison between combinations of droperidol-phenoperidine and chlorprothixene-dextromoramide in cardiac surgery]. After a quick review of the physiopathology of extra-corporeal circulation, the value of the use of neuroplegic drugs in cardiac surgery is recalled by means of pharmacological arguments. The experimental differences existing between the combinations droperidol - phenoperidine and chlorportixene - dextromoramide, on the rate of flow and on the pressure of the perfusion, and on the esophago-rectal thermic gradients during E.C.C. is then demonstrated. Statistic calculation confirmed the superiority of chlorprotixene in the realm of tissue perfusion during E.C.C. under hypothermia. | [
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|
PMID:16531 | [Drug protection of the myocardium during cardiac surgery]. | During aortic clamping, drug protection of the myocardium, far from supplanting hypothermia, complements it, particularly in the case of left ventricular hypertrophy. Ultramicroscopy and new techniques of histobiological exploration of the myocite have enabled one to distinguish the lessions provoked by anoxia from those induced by reperfusion. At present, drug protection, extended to energetic solutions and electrolytes, aim at preserving energy metabolism by stocking of the substrate and at avoiding interferences which precipitate exhaustion of the adenosine triphosphate and phosphocreatinine reserves. In order to do this, hemodilution in particular is limited in subjects with decompensated cardiopathy; choice of anesthetics is orientated towards neuroleptanalgesia or fluothane, and it is attempted to neutralize the adrenergic reaction by the use of beta-blocking substances. Furthermore, it is preferred to interrupt electrogenesis at the stage of polarization: depolarizing cardioplegic solutions rich in potassium and sodium are rejected and in preference membrane stabilizers are used (procaine, magnesium, tetrodoxine...) The ultramicroscopic analysis of the structural modifications leads to sparing of the integrity of the lysosomial membrane by corticoids and alkalines. The use of calcium is deferred, anti-calcium techniques are even proposed (washing poor in calcium, verapamil). Cellular edema is prevented and treated by solution (mannitol - sorbitol) whose osmolarity must be less than 300 M osm/l. A conditioning of the biochemical and physicial structures and of cardiac work is being more and more thought of which leads to the classification of beta stimulating substances as negative, and their indications must be seriously thought of and used with reserve. | [Drug protection of the myocardium during cardiac surgery]. During aortic clamping, drug protection of the myocardium, far from supplanting hypothermia, complements it, particularly in the case of left ventricular hypertrophy. Ultramicroscopy and new techniques of histobiological exploration of the myocite have enabled one to distinguish the lessions provoked by anoxia from those induced by reperfusion. At present, drug protection, extended to energetic solutions and electrolytes, aim at preserving energy metabolism by stocking of the substrate and at avoiding interferences which precipitate exhaustion of the adenosine triphosphate and phosphocreatinine reserves. In order to do this, hemodilution in particular is limited in subjects with decompensated cardiopathy; choice of anesthetics is orientated towards neuroleptanalgesia or fluothane, and it is attempted to neutralize the adrenergic reaction by the use of beta-blocking substances. Furthermore, it is preferred to interrupt electrogenesis at the stage of polarization: depolarizing cardioplegic solutions rich in potassium and sodium are rejected and in preference membrane stabilizers are used (procaine, magnesium, tetrodoxine...) The ultramicroscopic analysis of the structural modifications leads to sparing of the integrity of the lysosomial membrane by corticoids and alkalines. The use of calcium is deferred, anti-calcium techniques are even proposed (washing poor in calcium, verapamil). Cellular edema is prevented and treated by solution (mannitol - sorbitol) whose osmolarity must be less than 300 M osm/l. A conditioning of the biochemical and physicial structures and of cardiac work is being more and more thought of which leads to the classification of beta stimulating substances as negative, and their indications must be seriously thought of and used with reserve. | [
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|
PMID:16532 | [Shivering during recovery after cardiac surgery under extracorporeal circulation. Inconveniences and methods of prevention]. | Among 109 subjects who had undergone cardiac surgery under ECC, the authors recorded 50 (45 p. 100) who suffered from shivering during the coming round period. Comparing the series of patients who shivered, with that of the subjects who did not shiver, the authors demonstrate in the first case, an increase in cellular metabolism, the cardiac index, heart rate, central venous pressure and cardiac work. They subsequently note the apprearance of mixed acidosis and an increase in the lactate-pyruvate ratio. Certain patients, in whom the cardiac output did not keep up with the metabolic demand considerably increased the arterio-venous oxygen difference. Blood loss is increased as well as coagulation time showing a more intense heparin rebound. The study of the drugs used during anesthesia showed that the patients who had received chlorprotixene, as the neuroleptic, a neuroleptic with adrenolytic properties, had a very decreased frequency of shivering in comparison with those who had received droperidol. The placing of the patient at the end of the intervention on a heating mattress, combined with the administration of chlorprotixene during anesthesia, prevented the appearance of shivering. | [Shivering during recovery after cardiac surgery under extracorporeal circulation. Inconveniences and methods of prevention]. Among 109 subjects who had undergone cardiac surgery under ECC, the authors recorded 50 (45 p. 100) who suffered from shivering during the coming round period. Comparing the series of patients who shivered, with that of the subjects who did not shiver, the authors demonstrate in the first case, an increase in cellular metabolism, the cardiac index, heart rate, central venous pressure and cardiac work. They subsequently note the apprearance of mixed acidosis and an increase in the lactate-pyruvate ratio. Certain patients, in whom the cardiac output did not keep up with the metabolic demand considerably increased the arterio-venous oxygen difference. Blood loss is increased as well as coagulation time showing a more intense heparin rebound. The study of the drugs used during anesthesia showed that the patients who had received chlorprotixene, as the neuroleptic, a neuroleptic with adrenolytic properties, had a very decreased frequency of shivering in comparison with those who had received droperidol. The placing of the patient at the end of the intervention on a heating mattress, combined with the administration of chlorprotixene during anesthesia, prevented the appearance of shivering. | [
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|
PMID:16533 | [Preventive treatment of acute renal failure in cardiac surgery]. | The prevention of acute renal failure after cardiac surgery under extracorporeal circulation is possible during the pre-, per- and post-operative phases. During "ECC" the maintenance of "correct" renal perfusion is imperative, the same is also true of the post-operative period; the re-establishment of good hemodynamics is the best guarantee of maintenance of renal function. The prevention of infection is the second imperative. | [Preventive treatment of acute renal failure in cardiac surgery]. The prevention of acute renal failure after cardiac surgery under extracorporeal circulation is possible during the pre-, per- and post-operative phases. During "ECC" the maintenance of "correct" renal perfusion is imperative, the same is also true of the post-operative period; the re-establishment of good hemodynamics is the best guarantee of maintenance of renal function. The prevention of infection is the second imperative. | [
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PMID:16534 | [Deep hypothermia on the infant: physiopathology and technics of ECC]. | In 81 operations for correction of infants's cardiopathies, authors used, associated with E.C.C., a deep hypothermia allowing a circulatory arrest of an average duration of 52 minutes, according to the technics described by BARRAT-BOYES in 1971. From this experience, authors study the modifications brought to the organism by this hypothermia, and discuss the technical aspects in pre, per and post-operative periods. Mortality of this series is of 13,5 p. 100. It is in relation with the cardiopathy or it's correction, without anu possibility or directly charge the technique of hypothermia in its determinism. The early mortality includes a bilateral phrenic paralysis, an air embolism, three septic complications and two neurologic complications probably related to a poor thermic repartition. Advantages of this technique concern the possibility to operate in a bloodless field and a diminution of E.C.C. time. | [Deep hypothermia on the infant: physiopathology and technics of ECC]. In 81 operations for correction of infants's cardiopathies, authors used, associated with E.C.C., a deep hypothermia allowing a circulatory arrest of an average duration of 52 minutes, according to the technics described by BARRAT-BOYES in 1971. From this experience, authors study the modifications brought to the organism by this hypothermia, and discuss the technical aspects in pre, per and post-operative periods. Mortality of this series is of 13,5 p. 100. It is in relation with the cardiopathy or it's correction, without anu possibility or directly charge the technique of hypothermia in its determinism. The early mortality includes a bilateral phrenic paralysis, an air embolism, three septic complications and two neurologic complications probably related to a poor thermic repartition. Advantages of this technique concern the possibility to operate in a bloodless field and a diminution of E.C.C. time. | [
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|
PMID:16535 | [Cerebral arterial embolism during extracorporeal circulation]. | From October 1st 1970 to October 1st 1975, electrical and clinical post-operative observation of 1.700 operations under E.C.C. allowed record of E.E.G. and thus study incidents depending of cerebral embolism during their formation. 18 cases have been seen during E.C.C. and 2 at the stop of E.C.C. In 9 cases, it was an air embolus, in 4 others an atheromatous embolus. In the 7 remaining cases, origin of the embolus is uncertain, but probably gaseous. Semiology of the accident is first only E.E.G. In 10 cases, signs were minor, and moderate in 10 others, preceding a late but hard clinical symptomatology, frequently characterized by a delayed advent of epilepsy crisis. Later on, an annoying evolution of the accident was seen in 4 cases (1 death, 3 lasting neurologic deficiency). For the treatment, many observations confirm the highly beneficient part of early hyperbaric oxygen. | [Cerebral arterial embolism during extracorporeal circulation]. From October 1st 1970 to October 1st 1975, electrical and clinical post-operative observation of 1.700 operations under E.C.C. allowed record of E.E.G. and thus study incidents depending of cerebral embolism during their formation. 18 cases have been seen during E.C.C. and 2 at the stop of E.C.C. In 9 cases, it was an air embolus, in 4 others an atheromatous embolus. In the 7 remaining cases, origin of the embolus is uncertain, but probably gaseous. Semiology of the accident is first only E.E.G. In 10 cases, signs were minor, and moderate in 10 others, preceding a late but hard clinical symptomatology, frequently characterized by a delayed advent of epilepsy crisis. Later on, an annoying evolution of the accident was seen in 4 cases (1 death, 3 lasting neurologic deficiency). For the treatment, many observations confirm the highly beneficient part of early hyperbaric oxygen. | [
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|
PMID:16536 | [Brachial diplegia--a post ECC neurological complication of a specific type]. | Five cases of neurological disorders occurring after extra-corporeal circulation are presented owing to the singular nature of the clinical picture made up by the essential element of a progressive brachial diplegia, free from any sensory disorder. The topography of the lesion--single medullary lesion or bilateral encephalic--is discussed. An anatomic document enables the elimination of any médullary involvement in one of the cases, thus pointing to a bilateral central lesion. The physiopathological problems are looked at. | [Brachial diplegia--a post ECC neurological complication of a specific type]. Five cases of neurological disorders occurring after extra-corporeal circulation are presented owing to the singular nature of the clinical picture made up by the essential element of a progressive brachial diplegia, free from any sensory disorder. The topography of the lesion--single medullary lesion or bilateral encephalic--is discussed. An anatomic document enables the elimination of any médullary involvement in one of the cases, thus pointing to a bilateral central lesion. The physiopathological problems are looked at. | [
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PMID:16537 | [Early neurological complications after cardiac surgery under ECC]. | A non-trifling frequency (3,3 p. 100) of neurologic complications is observed after surgery under E.C.C. The part of some factors has been analysed and discussed, especially those played by the type of the system used, quality of the E.C.C., and the patients' conditions. Many problems are still unresolved. The actual gravity of observed troubles must bring a better harshness in preventive treatment, and to a more adjusted treatment when these troubles are noted. | [Early neurological complications after cardiac surgery under ECC]. A non-trifling frequency (3,3 p. 100) of neurologic complications is observed after surgery under E.C.C. The part of some factors has been analysed and discussed, especially those played by the type of the system used, quality of the E.C.C., and the patients' conditions. Many problems are still unresolved. The actual gravity of observed troubles must bring a better harshness in preventive treatment, and to a more adjusted treatment when these troubles are noted. | [
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|
PMID:16538 | [Pulmonary complications after extracorporeal circulation. ECC lung syndrome]. | Pulmonary complications after cardiac surgery under extracorporeal circulation remain frequent and sometimes grave, in spite of the great progress which has been made over the past 20 years in the methods of cardiorespiratory assistance. The authors analyse the clinical and radiological repercussions of perfusion on the lung, in 40 patients operated under ECC for coronary revascularisation. The simutaneous study of the arterial, and mixed venous blood gasses and of the alveolar gases, in 20 of these patients showed the constant occurrence of a shunt syndrome, without alveolar hypoventilation or disorders in peripheral circulatory flow. Ventilatory alcalosis, hypocapnia, hypoxemia and the rise in the alveolar arterial oxygen gradient is increased during the second post-operative day. Among the variables studied (duration of ECC, degree of hypothermia, duration of the intervention, duration of anesthesia, pleurotomy) only the latter intervened in a statistically significant manner in this study, in the increase in hypoxemia. 46 pulmonary biopsies carried out before and after ECC in 23 coronary patients were examined with the electron microscope. The initial alveolar involvement affects the septal microcirculation with signs of an increase in capillary permeability leading to an interstitial and epithelial destruction. The use of a membrane oxygenator prevents some of the alveolar lesions, as has been proved by the study of five pulmonary biopsies carried out in dogs submitted to ECC of long duration. Catherterization of the pulmonary artery carried out in 35 patients by means of a SWAN-GANZ catheter, before the intervention enabled supervision of the degree of importance and speed of the hemodynamic variations in the pulmonary circulation during the different phases of ECC (during the phase of ventricular fibrillation). The rise in the flow of left output can lead to the occurrence of negative pulmonary intravascular pressures which can be prejudicial for capillary trophicity. The syndrome of "ECC lung", a veritable "induced post-agressive lung" must be placed in the group of refractory hypoxemia of which it represents one of the most typical pictures. | [Pulmonary complications after extracorporeal circulation. ECC lung syndrome]. Pulmonary complications after cardiac surgery under extracorporeal circulation remain frequent and sometimes grave, in spite of the great progress which has been made over the past 20 years in the methods of cardiorespiratory assistance. The authors analyse the clinical and radiological repercussions of perfusion on the lung, in 40 patients operated under ECC for coronary revascularisation. The simutaneous study of the arterial, and mixed venous blood gasses and of the alveolar gases, in 20 of these patients showed the constant occurrence of a shunt syndrome, without alveolar hypoventilation or disorders in peripheral circulatory flow. Ventilatory alcalosis, hypocapnia, hypoxemia and the rise in the alveolar arterial oxygen gradient is increased during the second post-operative day. Among the variables studied (duration of ECC, degree of hypothermia, duration of the intervention, duration of anesthesia, pleurotomy) only the latter intervened in a statistically significant manner in this study, in the increase in hypoxemia. 46 pulmonary biopsies carried out before and after ECC in 23 coronary patients were examined with the electron microscope. The initial alveolar involvement affects the septal microcirculation with signs of an increase in capillary permeability leading to an interstitial and epithelial destruction. The use of a membrane oxygenator prevents some of the alveolar lesions, as has been proved by the study of five pulmonary biopsies carried out in dogs submitted to ECC of long duration. Catherterization of the pulmonary artery carried out in 35 patients by means of a SWAN-GANZ catheter, before the intervention enabled supervision of the degree of importance and speed of the hemodynamic variations in the pulmonary circulation during the different phases of ECC (during the phase of ventricular fibrillation). The rise in the flow of left output can lead to the occurrence of negative pulmonary intravascular pressures which can be prejudicial for capillary trophicity. The syndrome of "ECC lung", a veritable "induced post-agressive lung" must be placed in the group of refractory hypoxemia of which it represents one of the most typical pictures. | [
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|
PMID:16539 | [Technics of anesthesia and hypothermia for the infant. Choice of replacement fluid for the circuit]. | Sixty-five infants were submitted to complete repairment of a congenital cardiopathy under profound hypothermia and ECC. Description of the preparation of the young surgical patient, of the anesthesia, of the technique of ECC. The overall mortality was 35.5 p. 100. The hypothermia induced by ECC, does not introduce any supplementary risks as long as strict technical rules are respected. | [Technics of anesthesia and hypothermia for the infant. Choice of replacement fluid for the circuit]. Sixty-five infants were submitted to complete repairment of a congenital cardiopathy under profound hypothermia and ECC. Description of the preparation of the young surgical patient, of the anesthesia, of the technique of ECC. The overall mortality was 35.5 p. 100. The hypothermia induced by ECC, does not introduce any supplementary risks as long as strict technical rules are respected. | [
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PMID:16540 | [Use of a membrane oxygenator in extracorporeal circulation in the child. Preliminary conclusions]. | The comparison of two types of oxygenators, the bubble and membrane oxygenator, in cardiac surgery under ECC, in infants. The results were not subjected to a statistical study. However, it seems that the membrane oxygenator enables one to obtain a satisfactory hematosis in a simpler fashion (the addition of CO2 being avoided) than with the bubble oxygenator and leads to less hemolysis than the latter. In the cases of closed circuit ECC with recirculation, the use of the membrane oxygenator also gives greater security of manipulation of the blood mass. | [Use of a membrane oxygenator in extracorporeal circulation in the child. Preliminary conclusions]. The comparison of two types of oxygenators, the bubble and membrane oxygenator, in cardiac surgery under ECC, in infants. The results were not subjected to a statistical study. However, it seems that the membrane oxygenator enables one to obtain a satisfactory hematosis in a simpler fashion (the addition of CO2 being avoided) than with the bubble oxygenator and leads to less hemolysis than the latter. In the cases of closed circuit ECC with recirculation, the use of the membrane oxygenator also gives greater security of manipulation of the blood mass. | [
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|
PMID:16541 | [Fluid mass distribution during extracorporeal circulation]. | The author first recalls close relations existing in physiologic conditions between central venous pressure and blood mass. During E.C.C., this relation is out of truth through the action of venous correlations and of outout. Then studying distribution of blood mass in the different compartments, he notes that during E.C.C., the total organic fluid mass changes a little, but that the extracellular volume increases when the blood mass grows less. To these modifications shares in a seclusion of blood in the visceral compartment. | [Fluid mass distribution during extracorporeal circulation]. The author first recalls close relations existing in physiologic conditions between central venous pressure and blood mass. During E.C.C., this relation is out of truth through the action of venous correlations and of outout. Then studying distribution of blood mass in the different compartments, he notes that during E.C.C., the total organic fluid mass changes a little, but that the extracellular volume increases when the blood mass grows less. To these modifications shares in a seclusion of blood in the visceral compartment. | [
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|
PMID:16542 | [Proteins and blood volume after cardiac surgery under ECC and hemodilution]. | The variations in protein, bodyweight and circulating blood volume during operation are studied in 18 patients operated under ECC. The frequency of hypovolemia with hypoproteinemia and over hydration of the interstitial medium is confirmed. The prolongation of ECC beyond 120 minutes is accompanied by a considerable reduction in the plasma sector. The frequency of hypovolemia must render the use of diuretics prudent. The existence of hypoproteinemia and interstitial overload suggests the value of albumin perfusions. | [Proteins and blood volume after cardiac surgery under ECC and hemodilution]. The variations in protein, bodyweight and circulating blood volume during operation are studied in 18 patients operated under ECC. The frequency of hypovolemia with hypoproteinemia and over hydration of the interstitial medium is confirmed. The prolongation of ECC beyond 120 minutes is accompanied by a considerable reduction in the plasma sector. The frequency of hypovolemia must render the use of diuretics prudent. The existence of hypoproteinemia and interstitial overload suggests the value of albumin perfusions. | [
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PMID:16543 | [Direct action of extracorporeal circulation on platelets and coagulation factors]. | Concerning a study carried out in 250 patients, the authors confirm the classical notions concerning the fall in platelets, fibrinogenesis, factor II, XII AT3 and plasminogen during ECC. A more precise study of platelet levels shows important variations depending on the patients, whereas the length of time of ECC, the degree of importance of aspiration the first minutes of ECC, appear to be aggravating factors. There is no correlation between the type and the length of the circuit. Furthermore, from the morphological standpoint, thrombocytic changes are also noted. The same can be said of platelet function. In the last part of the work, the authors studied the causes of platelet consumption and their prevention. On the whole, and in practice, consumption of coagulation factors during ECC remains a little disturbing. It is, however, worth continuing to study their prevention. | [Direct action of extracorporeal circulation on platelets and coagulation factors]. Concerning a study carried out in 250 patients, the authors confirm the classical notions concerning the fall in platelets, fibrinogenesis, factor II, XII AT3 and plasminogen during ECC. A more precise study of platelet levels shows important variations depending on the patients, whereas the length of time of ECC, the degree of importance of aspiration the first minutes of ECC, appear to be aggravating factors. There is no correlation between the type and the length of the circuit. Furthermore, from the morphological standpoint, thrombocytic changes are also noted. The same can be said of platelet function. In the last part of the work, the authors studied the causes of platelet consumption and their prevention. On the whole, and in practice, consumption of coagulation factors during ECC remains a little disturbing. It is, however, worth continuing to study their prevention. | [
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|
PMID:16544 | [Coagulation deficits and hemorrhagic consequences after cardiac surgery under ECC]. | I--A statistical study of the results of tests of hemostasis was carried out in patients who had undergone major cardiac surgery with extra-corporeal circulation. There were two series of patients (1.504 and 547 operated) suffering mainly from congenital cardiopathies, valvulopathies or coronaritis. Bearing in mind the hematocrit and the total protein level, the following was studied before and after ECC and 24 hours after the intervation: the blood platelet level, fibrinogen, prothrombin and its cofactors, antithemophilic factors A and B, FDP amd fibrinolytic activity. The fall in platelet stickiness is specifically pointed out, and also the fall in the level of fibrin stablizing factor (factor XIII) which is met with after ECC, and which can explain the persistence of certain hemorrhagies. Furthermore, the fall in antithrombin III level then its rise can contribute to the "heparine rebound" occurring in certain cases after neutralization of heparinemia with protamine. II--The deficits in the quantitatively and qualitatively variable hemostatic factors do not necessarily lead to hemorrhage. Hemorrhage, due to biological causes, are met with in 5 to 6 p. 100 of the cases. Most of the time they are provoked by a residual hemorrhage or a "heparine rebound", deficits in coagulation factors, a DIVC syndrome, difficult to diagnose and to treat, or fibrinolysis, much more rarely nowadays, owing to the almost routine use of antiproteases. Sometimes, the check up of coagulation can be barely disturbed and local abnormalities in biological hemostasis which are still not well understood, are invoked in order to explain the hemorrhage. | [Coagulation deficits and hemorrhagic consequences after cardiac surgery under ECC]. I--A statistical study of the results of tests of hemostasis was carried out in patients who had undergone major cardiac surgery with extra-corporeal circulation. There were two series of patients (1.504 and 547 operated) suffering mainly from congenital cardiopathies, valvulopathies or coronaritis. Bearing in mind the hematocrit and the total protein level, the following was studied before and after ECC and 24 hours after the intervation: the blood platelet level, fibrinogen, prothrombin and its cofactors, antithemophilic factors A and B, FDP amd fibrinolytic activity. The fall in platelet stickiness is specifically pointed out, and also the fall in the level of fibrin stablizing factor (factor XIII) which is met with after ECC, and which can explain the persistence of certain hemorrhagies. Furthermore, the fall in antithrombin III level then its rise can contribute to the "heparine rebound" occurring in certain cases after neutralization of heparinemia with protamine. II--The deficits in the quantitatively and qualitatively variable hemostatic factors do not necessarily lead to hemorrhage. Hemorrhage, due to biological causes, are met with in 5 to 6 p. 100 of the cases. Most of the time they are provoked by a residual hemorrhage or a "heparine rebound", deficits in coagulation factors, a DIVC syndrome, difficult to diagnose and to treat, or fibrinolysis, much more rarely nowadays, owing to the almost routine use of antiproteases. Sometimes, the check up of coagulation can be barely disturbed and local abnormalities in biological hemostasis which are still not well understood, are invoked in order to explain the hemorrhage. | [
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|
PMID:16545 | [Variations in hemostasis in the infant under deep hypothermia]. | Effects on hemostasis of deep hypothermia on infant has been studied on 29 infants operated upon for a cardiopathy under deep hypothermia. Results of this study show a diminution of the coagulation factors rate, an augmentation of the fibrinolytic activity and an unforeseable variability of the residual heparin leading in all cases to a complement of the heparin neutralization by Protamine. | [Variations in hemostasis in the infant under deep hypothermia]. Effects on hemostasis of deep hypothermia on infant has been studied on 29 infants operated upon for a cardiopathy under deep hypothermia. Results of this study show a diminution of the coagulation factors rate, an augmentation of the fibrinolytic activity and an unforeseable variability of the residual heparin leading in all cases to a complement of the heparin neutralization by Protamine. | [
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PMID:16546 | [Physiopathology of low cardiac outputs after ECC and their treatment]. | Etiologic circumtances of low cardiac outputs are studied according as they concern a diminution of the precharge (hypovolemy of different reasons), an augmentation of the postcharge (by augmentation of aortic impedance or resistance to blood flow) or a cardiac deficiency. The latter can be of non-ischemic origin (effects of beta-blocking drugs, cardiac arrhytmias tamponade, deficience of myocardiac fiber, metabolic disease) or ischemic:--during E.C.C.: diminution of available oxygen (hypothermial), arterial pressure and output too low, clamping time or ventricular fibrillation too long;--after E.C.C.: insufficient surgical correction, coronary embolism lack of balance between apport and expense of oxygen. Therapeutics ways are discussed regarding the different etiologies. The central rule is that it is better to relieve an ischemic myocardia than lash it. But treatment of low cardiac outputs is most often an average solution which must be choose in regard to a well understood physiopathology. | [Physiopathology of low cardiac outputs after ECC and their treatment]. Etiologic circumtances of low cardiac outputs are studied according as they concern a diminution of the precharge (hypovolemy of different reasons), an augmentation of the postcharge (by augmentation of aortic impedance or resistance to blood flow) or a cardiac deficiency. The latter can be of non-ischemic origin (effects of beta-blocking drugs, cardiac arrhytmias tamponade, deficience of myocardiac fiber, metabolic disease) or ischemic:--during E.C.C.: diminution of available oxygen (hypothermial), arterial pressure and output too low, clamping time or ventricular fibrillation too long;--after E.C.C.: insufficient surgical correction, coronary embolism lack of balance between apport and expense of oxygen. Therapeutics ways are discussed regarding the different etiologies. The central rule is that it is better to relieve an ischemic myocardia than lash it. But treatment of low cardiac outputs is most often an average solution which must be choose in regard to a well understood physiopathology. | [
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|
PMID:16547 | [Hemodynamic aspect of post ECC cardiac failures. Study of 193 cases]. | The aim of this study is to define the hemodynamic characteristics of this "clinical model" of acute cardiac failure observed after cardiac surgery carried out under extra-corporeal circulation, which constitutes the essential cause of "post-operative low cardiac output syndrome". The 193 patients in this study make up a representative sample of patients operated, treated and studied according to a homogeneous methodology for a period of 1 year. The clinical analysis of the post-operative circulatory condition, after exclusion of non cardiogenic syndromes, led to grouping the cases into 5 classes of circulatory change of increasing severity, each corresponding to a specific "therapeutic necessity". The hemodynamic results (intra-vascular pressures, oxymetry, cardiac output by "Cardio-Green" dilution method) are given for each of the five classes, thus defining the "hemodynamic profile" and the statistical reliability of the main objective parameters. This gives proof of the therapeutic indications for the main therapeutic procedures actually known, for which we prevent the hemodynamic effects noted for each of them. Thus, three "degrees of cardiac failure" are found: less severe (classes I and II) call for simple metabolic equilibration and possibly diuretics: the systolic work is above 160 gm/m2. Decompensated circulatory failure (classes III and IV) corresponds to a more important reduction in systolic work (9) 15 gm/m2, i.e. between 20 et 40 p. 100 of the basal value), and call for sympatho-mimetic cardiotonic agents: isoprenaline and/or dopamine. Below this value, in spite of medical treatment, the hemodynamic situation can still be sometimes reversible under circulatory assistance (diastolic counter pressure by means of an aortic balloon). Confronted with the clinical picture, the hemodynamic study enables the quantification of the circulatory change, and specification of the cardiogenic part and thus especially helps the carrying out of the treatment. | [Hemodynamic aspect of post ECC cardiac failures. Study of 193 cases]. The aim of this study is to define the hemodynamic characteristics of this "clinical model" of acute cardiac failure observed after cardiac surgery carried out under extra-corporeal circulation, which constitutes the essential cause of "post-operative low cardiac output syndrome". The 193 patients in this study make up a representative sample of patients operated, treated and studied according to a homogeneous methodology for a period of 1 year. The clinical analysis of the post-operative circulatory condition, after exclusion of non cardiogenic syndromes, led to grouping the cases into 5 classes of circulatory change of increasing severity, each corresponding to a specific "therapeutic necessity". The hemodynamic results (intra-vascular pressures, oxymetry, cardiac output by "Cardio-Green" dilution method) are given for each of the five classes, thus defining the "hemodynamic profile" and the statistical reliability of the main objective parameters. This gives proof of the therapeutic indications for the main therapeutic procedures actually known, for which we prevent the hemodynamic effects noted for each of them. Thus, three "degrees of cardiac failure" are found: less severe (classes I and II) call for simple metabolic equilibration and possibly diuretics: the systolic work is above 160 gm/m2. Decompensated circulatory failure (classes III and IV) corresponds to a more important reduction in systolic work (9) 15 gm/m2, i.e. between 20 et 40 p. 100 of the basal value), and call for sympatho-mimetic cardiotonic agents: isoprenaline and/or dopamine. Below this value, in spite of medical treatment, the hemodynamic situation can still be sometimes reversible under circulatory assistance (diastolic counter pressure by means of an aortic balloon). Confronted with the clinical picture, the hemodynamic study enables the quantification of the circulatory change, and specification of the cardiogenic part and thus especially helps the carrying out of the treatment. | [
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|
PMID:16548 | [Acute renal failure after cardiac surgery under extracorporeal circulation]. | Acute renal failure (ARF) following cardiac surgery under extra-corporeal circulation is a grave but infrequent complication. Numerous physiopathological factors accounting for its origin are analyzed, those related to ECC and those of the immediate post-operative period. The course of these cares of ARF and the elements of the treatment are looked at. | [Acute renal failure after cardiac surgery under extracorporeal circulation]. Acute renal failure (ARF) following cardiac surgery under extra-corporeal circulation is a grave but infrequent complication. Numerous physiopathological factors accounting for its origin are analyzed, those related to ECC and those of the immediate post-operative period. The course of these cares of ARF and the elements of the treatment are looked at. | [
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|
PMID:16549 | [Kidney failure after ectracorporeal circulation in cardiac surgery]. | The renal function of 113 patients undergoing cardiac surgery under ECC was studied. In 32 p. 100 of the cases renal involvement was noted which was moderate in 18 p. 100 of the cases, severe in 10 p. 100 of the cases and anuric in 4 p. 100 of the cases. Valvular surgery was complicated once in every three cases by renal involvement, the repair of congenital malformations once out of every two cases, and coronary surgery in 17 p. 100 of the cases. The fall in renal perfusion represents the essential factor in this renal involvement, which should be avoided by the maintenace during ECC of a high output level and a satisfactory perfusion pressure and by the recovery of correct hemodynamics after the intervention. | [Kidney failure after ectracorporeal circulation in cardiac surgery]. The renal function of 113 patients undergoing cardiac surgery under ECC was studied. In 32 p. 100 of the cases renal involvement was noted which was moderate in 18 p. 100 of the cases, severe in 10 p. 100 of the cases and anuric in 4 p. 100 of the cases. Valvular surgery was complicated once in every three cases by renal involvement, the repair of congenital malformations once out of every two cases, and coronary surgery in 17 p. 100 of the cases. The fall in renal perfusion represents the essential factor in this renal involvement, which should be avoided by the maintenace during ECC of a high output level and a satisfactory perfusion pressure and by the recovery of correct hemodynamics after the intervention. | [
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|
PMID:16550 | L(+) lactate dehydrogenase activity from the electric organ of Electrophorus electricus (L.). | Properties of L(+) lactate dehydrogenase (LDH) of Electrophorus electricus (L.) electric organ were studied, comparing the substrates pyruvate and lactate. Electric organ LDH is a soluble enzyme with a pH optimum of 7.4 for pyruvate and 9.0 for lactate. The apparent Km was lower for pyruvate (Km = 2.5 X 10(-4) M) than for lactate (Km = 1.5 X 10(-2) M). With lactate as a substrate at pH 7.4, malonate, oxalate and pyruvate inhibited competitively. For pyruvate as substrate at pH 9.0 malonate inhibited non-competitively and oxalate shiwed uncompetitive inhibition. The different effects of the carboxylic acids on LDH activity suggest different stereospecificities of the two enzyme-coenzyme complexes in the forward and reserve reactions. The reactions of electric organ LDH with substrates and inhibitors are consistent with electrophoretic analysis suggesting that the enzyme is of the M-type. | L(+) lactate dehydrogenase activity from the electric organ of Electrophorus electricus (L.). Properties of L(+) lactate dehydrogenase (LDH) of Electrophorus electricus (L.) electric organ were studied, comparing the substrates pyruvate and lactate. Electric organ LDH is a soluble enzyme with a pH optimum of 7.4 for pyruvate and 9.0 for lactate. The apparent Km was lower for pyruvate (Km = 2.5 X 10(-4) M) than for lactate (Km = 1.5 X 10(-2) M). With lactate as a substrate at pH 7.4, malonate, oxalate and pyruvate inhibited competitively. For pyruvate as substrate at pH 9.0 malonate inhibited non-competitively and oxalate shiwed uncompetitive inhibition. The different effects of the carboxylic acids on LDH activity suggest different stereospecificities of the two enzyme-coenzyme complexes in the forward and reserve reactions. The reactions of electric organ LDH with substrates and inhibitors are consistent with electrophoretic analysis suggesting that the enzyme is of the M-type. | [
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|
PMID:16554 | Influence of reagent quality and reaction conditions on the determination of serum albumin by the bromcresol green dye-binding method. | In an age of reference methodologies and sophisticated quality control techniques it is surprising that so little attention is paid to the quality of the reagents that are used. This paper reports on an investigation of the bromcresol green dye-binding procedure for the estimation of serum albumin in which particular attention has been paid to changes in the reagent components that contribute to the performance of the method. It has been shown that detailed attention to the quality control of the reagents can improve the precision and interlaboratory comparison in the estimation of serum albumin. | Influence of reagent quality and reaction conditions on the determination of serum albumin by the bromcresol green dye-binding method. In an age of reference methodologies and sophisticated quality control techniques it is surprising that so little attention is paid to the quality of the reagents that are used. This paper reports on an investigation of the bromcresol green dye-binding procedure for the estimation of serum albumin in which particular attention has been paid to changes in the reagent components that contribute to the performance of the method. It has been shown that detailed attention to the quality control of the reagents can improve the precision and interlaboratory comparison in the estimation of serum albumin. | [
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|
PMID:16558 | [Endocrine polyadenomatosis associated with prolactin pituitary adenoma and an intrathyroidal parathyroid adenoma]. | A pituitary adenoma was removed transsphenoidally from a 20-yr-old woman with secondary amenorrhea, galactorrhea, and hyperprolactinemia. Light and electronic microscopy, immunocytology characterized a prolactin cell tumor. The patient also underwent three surgical explorations for hyperparathyroidism. Only after selective catheterization of thyroid veins with radioimmunoassay for parathormone, an intrathyroidal parathyroid adenoma was found. No other case of proven prolactin adenoma in Wermer's syndrome has been reported. | [Endocrine polyadenomatosis associated with prolactin pituitary adenoma and an intrathyroidal parathyroid adenoma]. A pituitary adenoma was removed transsphenoidally from a 20-yr-old woman with secondary amenorrhea, galactorrhea, and hyperprolactinemia. Light and electronic microscopy, immunocytology characterized a prolactin cell tumor. The patient also underwent three surgical explorations for hyperparathyroidism. Only after selective catheterization of thyroid veins with radioimmunoassay for parathormone, an intrathyroidal parathyroid adenoma was found. No other case of proven prolactin adenoma in Wermer's syndrome has been reported. | [
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|
PMID:16559 | Renal function during and following obstruction. | The effects of urinary-tract obstruction on renal function have been clarified using modern physiologic techniques in animal models. These effects are obviously dependent on the severity and duration of obstruction, together with the presence or absence of extrarenal factors, particularly uremia, as exemplified by the differences in renal function between bilateral and unilateral obstruction. The beneficial effects on the unilateral postobstructive kidney of volume expansion (5) and the importance of azotemia in determining POD (20, 21) have possible clinical applications. Further experimental work is required to understand the mechanism responsible for the altered renal hemodynamics and decreased GFR, as well as the abnormalities in medullary function resulting from obstruction. Improvement in the management of this common clinical problem may then be forthcoming. | Renal function during and following obstruction. The effects of urinary-tract obstruction on renal function have been clarified using modern physiologic techniques in animal models. These effects are obviously dependent on the severity and duration of obstruction, together with the presence or absence of extrarenal factors, particularly uremia, as exemplified by the differences in renal function between bilateral and unilateral obstruction. The beneficial effects on the unilateral postobstructive kidney of volume expansion (5) and the importance of azotemia in determining POD (20, 21) have possible clinical applications. Further experimental work is required to understand the mechanism responsible for the altered renal hemodynamics and decreased GFR, as well as the abnormalities in medullary function resulting from obstruction. Improvement in the management of this common clinical problem may then be forthcoming. | [
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|
PMID:16560 | Effect of anesthetic drugs on myocardial performance in man. | All potent CNS depressant drugs can depress cardiac function in man in a dose-dependent manner. The dose-effect curve is considerably flatter with several drugs (diethyl ether, cyclopropane, fluroxene, isoflurane, and ketamine), presumably from sympathetic nervous-system activation. Potent analgesics and tranquilizers appear to produce less depression, but have been incompletely studied. Neuromuscular blocking drugs and regional anesthesia produce minimal effects on the heart in healthy people. However, not as much is known about diseased man. For instance, nitrous oxide produces more depression in "muscle" function in IHD patients (43), while diazepam (28) and morphine (44) do not adversely affect pump function in this class of patients. Fluroxene (45) is more depressant in VHD patients, but nitrous oxide (46), morphine (30), fetanyl (46), and droperidol-fentanyl (46) seem to have equivalent effects to those seen in health patients. In any given patient, therefore, accurate prediction of the effect of any anesthetic drug on cardiac performance is not possible. Adequate monitoring and careful titration of drug dose offer the safest method of assuring a satisfactory response. | Effect of anesthetic drugs on myocardial performance in man. All potent CNS depressant drugs can depress cardiac function in man in a dose-dependent manner. The dose-effect curve is considerably flatter with several drugs (diethyl ether, cyclopropane, fluroxene, isoflurane, and ketamine), presumably from sympathetic nervous-system activation. Potent analgesics and tranquilizers appear to produce less depression, but have been incompletely studied. Neuromuscular blocking drugs and regional anesthesia produce minimal effects on the heart in healthy people. However, not as much is known about diseased man. For instance, nitrous oxide produces more depression in "muscle" function in IHD patients (43), while diazepam (28) and morphine (44) do not adversely affect pump function in this class of patients. Fluroxene (45) is more depressant in VHD patients, but nitrous oxide (46), morphine (30), fetanyl (46), and droperidol-fentanyl (46) seem to have equivalent effects to those seen in health patients. In any given patient, therefore, accurate prediction of the effect of any anesthetic drug on cardiac performance is not possible. Adequate monitoring and careful titration of drug dose offer the safest method of assuring a satisfactory response. | [
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|
PMID:16561 | [Synthetic medium for the biosynthesis of gentamicin]. | A synthetic medium for biosynthesis of gentamicin was developed. It includes maltose, gelatine, potassium phosphate, ammonium sulphate, cobalt chloride, sodium chloride, magnesium sulphate and zinc sulphate. The dynamics of the biochemical changes in the above medium was studied. | [Synthetic medium for the biosynthesis of gentamicin]. A synthetic medium for biosynthesis of gentamicin was developed. It includes maltose, gelatine, potassium phosphate, ammonium sulphate, cobalt chloride, sodium chloride, magnesium sulphate and zinc sulphate. The dynamics of the biochemical changes in the above medium was studied. | [
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|
PMID:16562 | [Penicillin amidase from E. coli. Some physicochemical properties of the soluble enzyme]. | Homogeneity of the enzyme was shown with the methods of gel filtration and disc electrophoresis. The molecular mass of penicillinamidase (PA) was determined. Sorption of PA by a carboxylic ion exchanger within a wide range of pH was studied. The values of pH in the ion exchanger phase under the conditions of the enzyme sorption were estimated. The ion exchange technique for determination of the isoelectric points of the proteins is described and the isoelectric point of PA is determined. It is proposed to use the method for estimation of close ionization constants of amphoteric an weak electrolites for interpretation of the bell-like pH dependence of kinetic and equilibrium parameters of the enzymatic reaction. The ionization constants of Michaelis complex of PA were evaluated. The activation energy of benzylpenicillin hydrolysis catalized by PA was determined. | [Penicillin amidase from E. coli. Some physicochemical properties of the soluble enzyme]. Homogeneity of the enzyme was shown with the methods of gel filtration and disc electrophoresis. The molecular mass of penicillinamidase (PA) was determined. Sorption of PA by a carboxylic ion exchanger within a wide range of pH was studied. The values of pH in the ion exchanger phase under the conditions of the enzyme sorption were estimated. The ion exchange technique for determination of the isoelectric points of the proteins is described and the isoelectric point of PA is determined. It is proposed to use the method for estimation of close ionization constants of amphoteric an weak electrolites for interpretation of the bell-like pH dependence of kinetic and equilibrium parameters of the enzymatic reaction. The ionization constants of Michaelis complex of PA were evaluated. The activation energy of benzylpenicillin hydrolysis catalized by PA was determined. | [
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|
PMID:16563 | [Penicillin amidase from E. coli. Some physicochemical properties of the enzyme incorporated into polyacrylamide gel]. | The physico-chemical properties of penicillinamidase (PA) immobilized in polyacrylamide gel (IPA) were investigated. It was shown that simple incorporation of PA into polyacrylamide gel was not effective because of gradual washing out of the enzyme. The use of a complex method for the immobilization (immobilization in the presence of a linking agent) resulted in higher stability of IPA, the choice of the optimal ratio of the reagents being of paramount importance. The mechanical strength of IPA was studied in model experiments. | [Penicillin amidase from E. coli. Some physicochemical properties of the enzyme incorporated into polyacrylamide gel]. The physico-chemical properties of penicillinamidase (PA) immobilized in polyacrylamide gel (IPA) were investigated. It was shown that simple incorporation of PA into polyacrylamide gel was not effective because of gradual washing out of the enzyme. The use of a complex method for the immobilization (immobilization in the presence of a linking agent) resulted in higher stability of IPA, the choice of the optimal ratio of the reagents being of paramount importance. The mechanical strength of IPA was studied in model experiments. | [
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|
PMID:16564 | Penicillin resistance and penicillinase production in clinical isolates of Bacteroides melaninogenicus. | The minimum inhibitory concentrations (MIC) of penicillin and six other antimicrobials were determined for 50 clinical isolates of Bacteroides melaninogenicus. Agar dilution susceptibilities were performed using supplemented brucella blood agar and the proposed National Committee for Clinical Laboratory Standards standard method for anaerobes; results with the two methods were comparable. A penicillin concentration >/=0.8 mug/ml was needed to inhibit 56% of the isolates, whereas 100% were susceptible to 0.1 mug of clindamycin per ml. All isolates with penicillin MIC values >/=0.8 mug/ml produced beta-lactamase using a slide method. A micro-iodometric assay was used to quantitate beta-lactamase production in six isolates. The beta-lactamase activity of B. melaninogenicus was comparable to that of a Staphylococcus aureus isolate but was not inducible, and the specific amount produced correlated only partially with penicillin MIC values. A clinical review of patients from whom the beta-lactamase-producing strains of B. melaninogenicus were isolated did not suggest any increased virulence in these strains or an unexpectedly poor clinical response to appropriate therapy. | Penicillin resistance and penicillinase production in clinical isolates of Bacteroides melaninogenicus. The minimum inhibitory concentrations (MIC) of penicillin and six other antimicrobials were determined for 50 clinical isolates of Bacteroides melaninogenicus. Agar dilution susceptibilities were performed using supplemented brucella blood agar and the proposed National Committee for Clinical Laboratory Standards standard method for anaerobes; results with the two methods were comparable. A penicillin concentration >/=0.8 mug/ml was needed to inhibit 56% of the isolates, whereas 100% were susceptible to 0.1 mug of clindamycin per ml. All isolates with penicillin MIC values >/=0.8 mug/ml produced beta-lactamase using a slide method. A micro-iodometric assay was used to quantitate beta-lactamase production in six isolates. The beta-lactamase activity of B. melaninogenicus was comparable to that of a Staphylococcus aureus isolate but was not inducible, and the specific amount produced correlated only partially with penicillin MIC values. A clinical review of patients from whom the beta-lactamase-producing strains of B. melaninogenicus were isolated did not suggest any increased virulence in these strains or an unexpectedly poor clinical response to appropriate therapy. | [
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|
PMID:16571 | Clinical and histological study of coal tar phototoxicity in humans. | Coal tars of different origin were compared with regard to their capacity to cause a phototoxic reaction in human skin. The photosensitizing potencies were found to differ. Tars that were partially refined had less activity than crude coal tar. An extract of tar, liquor carbonis detergens, was the least photosensitizing. The phototoxic reaction to coal tar was found to be a two-stage process, an immediate wheal associated with sharp burning, followed by a raised, red, infiltrated lesion peaking at 24 to 48 hours. The phototoxic reaction was completely prevented when arterial blood flow was cut off. The histological findings were prominently epidermal, with strong intracellular edema sometimes leading to microvesicles. It seems a possibility that assaying phototoxic potentiality may provide a convenient measure of therapeutic efficacy of materials derived from coal tar. | Clinical and histological study of coal tar phototoxicity in humans. Coal tars of different origin were compared with regard to their capacity to cause a phototoxic reaction in human skin. The photosensitizing potencies were found to differ. Tars that were partially refined had less activity than crude coal tar. An extract of tar, liquor carbonis detergens, was the least photosensitizing. The phototoxic reaction to coal tar was found to be a two-stage process, an immediate wheal associated with sharp burning, followed by a raised, red, infiltrated lesion peaking at 24 to 48 hours. The phototoxic reaction was completely prevented when arterial blood flow was cut off. The histological findings were prominently epidermal, with strong intracellular edema sometimes leading to microvesicles. It seems a possibility that assaying phototoxic potentiality may provide a convenient measure of therapeutic efficacy of materials derived from coal tar. | [
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|
PMID:16574 | Comparison of the effects of alclofenac, flurbiprofen, and prednisolone on acute inflammatory response in the rat. | The fluid and cellular phases of the inflammatory response were measured using a technique employing subcutaneous implantation of polyurethane foam cubes impregnated with heat-killed Mycobacterium tuberculosis. Fluribiprofen and prednisolone were equipotent and were capable of almost completely suppressing fluid and cellular responses, while alclofenac was less potent at nontoxic dose levels. Study of the patterns of cellular exudation by image analysing computer showed that alcofenac appears unique in that it produces a well-defined cell-free zone between the edge of the implanted cubes and a band of neutrophil polymorphs within the cubes. | Comparison of the effects of alclofenac, flurbiprofen, and prednisolone on acute inflammatory response in the rat. The fluid and cellular phases of the inflammatory response were measured using a technique employing subcutaneous implantation of polyurethane foam cubes impregnated with heat-killed Mycobacterium tuberculosis. Fluribiprofen and prednisolone were equipotent and were capable of almost completely suppressing fluid and cellular responses, while alclofenac was less potent at nontoxic dose levels. Study of the patterns of cellular exudation by image analysing computer showed that alcofenac appears unique in that it produces a well-defined cell-free zone between the edge of the implanted cubes and a band of neutrophil polymorphs within the cubes. | [
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|
PMID:16576 | Alpha-Isopropylmalate synthase from Alcaligenes eutrophus H 16 I. Purification and general properties. | alpha-Isopropylmalate (IPM) synthase, the first enzyme in the biosynthesis of L-leucine, was purified to a specific activity of 12 micronmole/min x mg protein from the valine-isoleucine double auxotrophic mutant A-81 of the hydrogen bacterium Alcaligenes eutrophus H16. The activity in crude extracts of derepressed cells was 0.106 micronmoles of isopropylmalate formed per min and per mg protein. Gel electrophoresis and regel electrophoresis of the isolated main band resulted in several distinct bands, which were not altered by the additions of substrate alpha-ketoisovalerate, feedback inhibitor leucine or other effectors. The isoelectric points of the enzyme protein was between 3.9 and 4.0. The molecular weight was 114 500 daltons and 100 000 respectively in the absence and presence of the feedback inhibitor leucine. The enzyme activity depended strongly on the pH, the optimum is at pH 8.2. The enzyme was could labile and exhibits temperature anomalies. | Alpha-Isopropylmalate synthase from Alcaligenes eutrophus H 16 I. Purification and general properties. alpha-Isopropylmalate (IPM) synthase, the first enzyme in the biosynthesis of L-leucine, was purified to a specific activity of 12 micronmole/min x mg protein from the valine-isoleucine double auxotrophic mutant A-81 of the hydrogen bacterium Alcaligenes eutrophus H16. The activity in crude extracts of derepressed cells was 0.106 micronmoles of isopropylmalate formed per min and per mg protein. Gel electrophoresis and regel electrophoresis of the isolated main band resulted in several distinct bands, which were not altered by the additions of substrate alpha-ketoisovalerate, feedback inhibitor leucine or other effectors. The isoelectric points of the enzyme protein was between 3.9 and 4.0. The molecular weight was 114 500 daltons and 100 000 respectively in the absence and presence of the feedback inhibitor leucine. The enzyme activity depended strongly on the pH, the optimum is at pH 8.2. The enzyme was could labile and exhibits temperature anomalies. | [
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|
PMID:16577 | Adenosine-5'-phosphosulfate (APS) as sulfate donor for assimilatory sulfate reduction in Rhodospirillum rubrum. | Crude extracts of Rhodospirillum rubrum catalyzed the formation of acid-volatile radioactivity from (35S) sulfate, (35S) adenosine-5'-phosphosulfate, and (35S) 3'-phosphoadenosine-5'-phosphosulfate. An enzyme fraction similar to APS-sulfotransferases from plant sources was purified 228-fold from Rhodospirillum rubrum. It is suggested here that this enzyme is specific for adenosine-5'-phosphosulfate, because the purified enzyme fraction metabolized adenosine-5'-phosphosulfate; 3'-phosphoadenosine-5'-phosphosulfate, however, only at a rate of 1/10 of that with adenosine-5'-phosphosulfate. Further, the reaction with 3'-phosphoadenosine-5'-phosphosulfate was inhibited with 3'-phosphoadenosine-5'-phosphate whereas this nucleotide had no effect on the reaction with adenosine-5'-phosphosulfate. For this activity with adenosine-5'-phosphosulfate the name APS-sulfotransferase is suggested. This APS-sulfotransferase needs thiols for activity; good rates were obtained with either dithioerythritol or reduced glutathione; other thiols like cysteine, 2'-3'-dimercaptopropanol or mercaptoethanol are less effective. The electron donor methylviologen did not catalyze this reaction. The pH-optimum was about 9.0; the apparent Km for adenosine-5'phosphosulfate was determined to be 0.05 mM with this so far purified enzyme fraction. Enzyme activity was increased with K2SO4 and Na2SO4 and was inhibited by 5'-AMP. These properties are similar to assimilatory APS-sulfotransferases from spinach and Chlorella. | Adenosine-5'-phosphosulfate (APS) as sulfate donor for assimilatory sulfate reduction in Rhodospirillum rubrum. Crude extracts of Rhodospirillum rubrum catalyzed the formation of acid-volatile radioactivity from (35S) sulfate, (35S) adenosine-5'-phosphosulfate, and (35S) 3'-phosphoadenosine-5'-phosphosulfate. An enzyme fraction similar to APS-sulfotransferases from plant sources was purified 228-fold from Rhodospirillum rubrum. It is suggested here that this enzyme is specific for adenosine-5'-phosphosulfate, because the purified enzyme fraction metabolized adenosine-5'-phosphosulfate; 3'-phosphoadenosine-5'-phosphosulfate, however, only at a rate of 1/10 of that with adenosine-5'-phosphosulfate. Further, the reaction with 3'-phosphoadenosine-5'-phosphosulfate was inhibited with 3'-phosphoadenosine-5'-phosphate whereas this nucleotide had no effect on the reaction with adenosine-5'-phosphosulfate. For this activity with adenosine-5'-phosphosulfate the name APS-sulfotransferase is suggested. This APS-sulfotransferase needs thiols for activity; good rates were obtained with either dithioerythritol or reduced glutathione; other thiols like cysteine, 2'-3'-dimercaptopropanol or mercaptoethanol are less effective. The electron donor methylviologen did not catalyze this reaction. The pH-optimum was about 9.0; the apparent Km for adenosine-5'phosphosulfate was determined to be 0.05 mM with this so far purified enzyme fraction. Enzyme activity was increased with K2SO4 and Na2SO4 and was inhibited by 5'-AMP. These properties are similar to assimilatory APS-sulfotransferases from spinach and Chlorella. | [
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|
PMID:16578 | Allohydroxy-D-proline dehydrogenase. An inducible membrane-bound enzyme in Pseudomonas aeruginosa PA01. | Growth of Pseudomonas aeruginosa PA01 on isomers of hydroxyproline induced the synthesis of an allohydroxy-D-proline dehydrogenase. The enzyme resembled the D-alanine dehydrogenase of this organism in its association with the particulate fraction and its linkage to oxygen through a cytochrome-containing respiratory chain, but differed from this and other bacterial D-amino acid dehydrogenases in its high substrate specificity and low Km. | Allohydroxy-D-proline dehydrogenase. An inducible membrane-bound enzyme in Pseudomonas aeruginosa PA01. Growth of Pseudomonas aeruginosa PA01 on isomers of hydroxyproline induced the synthesis of an allohydroxy-D-proline dehydrogenase. The enzyme resembled the D-alanine dehydrogenase of this organism in its association with the particulate fraction and its linkage to oxygen through a cytochrome-containing respiratory chain, but differed from this and other bacterial D-amino acid dehydrogenases in its high substrate specificity and low Km. | [
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|
PMID:16580 | Neurophysiologic and pathologic aspects of acute and chronic pain. | Acute pain produced by disease or injury is the net effect of highly complex interactions of various neural systems and psychological factors. Through the interaction of the afferent systems and neocortical processes, the individual is provided perceptual information regarding location, magnitude, and spatial and temporal properties of the noxious stimulus that activates motivational tendencies toward escape or attack and permits analysis of multimodal information, past experience, and probability of outcome of different response strategies. In contrast, chronic pain is a malefic force that taxes the physical, emotional, and economic resources of the patient, his famiily, and society. Moreover, chronic pain is characterized by physiological affective and behavioral responses that are quite different than those of acute pain. The clinician must keep these differences in mind in order to provide patients with optimal relief of their pain. | Neurophysiologic and pathologic aspects of acute and chronic pain. Acute pain produced by disease or injury is the net effect of highly complex interactions of various neural systems and psychological factors. Through the interaction of the afferent systems and neocortical processes, the individual is provided perceptual information regarding location, magnitude, and spatial and temporal properties of the noxious stimulus that activates motivational tendencies toward escape or attack and permits analysis of multimodal information, past experience, and probability of outcome of different response strategies. In contrast, chronic pain is a malefic force that taxes the physical, emotional, and economic resources of the patient, his famiily, and society. Moreover, chronic pain is characterized by physiological affective and behavioral responses that are quite different than those of acute pain. The clinician must keep these differences in mind in order to provide patients with optimal relief of their pain. | [
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|
PMID:16581 | [Ultrastructure of the parietal cells of the gastric mucosa in ulcer disease of the duodenum with a hyperacid syndrome (ultrastructurometric study)]. | An electron-microscopy investigation and morphometric analysis were carried out in 30 specimens of bioptic material of the fundal part of the stomach in patients with duodenal ulcer with the hyperacid syndrome. At all levels of the Major gastric glands parietal cells with morphological signs of intensive secretory activity prevailed, which was one of the causes (apart from the increase in the mass of parietal cells) of considerable intensification of secretion of hydrochloric acid. It was suggested that a considerably increased (as compared with the norm) area of the surface of the crysts of mitochondria with simultaneous reduction of the coefficient of their fragmentation was the morphological substrate of a high functional activity of parietal cells of the gastric mucosa in the hyperacid syndrome. | [Ultrastructure of the parietal cells of the gastric mucosa in ulcer disease of the duodenum with a hyperacid syndrome (ultrastructurometric study)]. An electron-microscopy investigation and morphometric analysis were carried out in 30 specimens of bioptic material of the fundal part of the stomach in patients with duodenal ulcer with the hyperacid syndrome. At all levels of the Major gastric glands parietal cells with morphological signs of intensive secretory activity prevailed, which was one of the causes (apart from the increase in the mass of parietal cells) of considerable intensification of secretion of hydrochloric acid. It was suggested that a considerably increased (as compared with the norm) area of the surface of the crysts of mitochondria with simultaneous reduction of the coefficient of their fragmentation was the morphological substrate of a high functional activity of parietal cells of the gastric mucosa in the hyperacid syndrome. | [
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|
PMID:16582 | Parkinson's disease. | The classical clinical picture of Parkinson's disease is all too frequently encountered in the elderly patient. The modern classification of causes of Parkinson's disease lists 'idiopathic', and 'post-encephalitic forms', the latter being uncommon in this community. | Parkinson's disease. The classical clinical picture of Parkinson's disease is all too frequently encountered in the elderly patient. The modern classification of causes of Parkinson's disease lists 'idiopathic', and 'post-encephalitic forms', the latter being uncommon in this community. | [
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|
PMID:16579 | [Carbohydrate-dependent lipidogenesis. Review of the literature and experimental study]. | The literature on glycide-induced lipidogenesis is reviewed. This is an important question also because of its relation to the pathogenesis of pathological conditions such as ketoacidosis, obesity and hypertriglyceridaemia. Doubt is expressed concerning the interpretation of some experimental procedures used in determining the extent of lipidogenesis in man. The questions raised are fully discussed. Their solution is sought via an experiment on the rat involving the comparison of tissue and plasma lipid metabolites values following infusion of a labelled glucose bolus. Little correlation was noted, low plasma levels being found with high tissue radioactivity. It is emphasized that it is very difficult to ideate a valid experimental approach in order to investigate the extent of lipidogenesis in man in vivo: in this respect, the long term risk arising from the use of tracers with a very long half-life (e.g. 14C) in man must be carefully valuated. | [Carbohydrate-dependent lipidogenesis. Review of the literature and experimental study]. The literature on glycide-induced lipidogenesis is reviewed. This is an important question also because of its relation to the pathogenesis of pathological conditions such as ketoacidosis, obesity and hypertriglyceridaemia. Doubt is expressed concerning the interpretation of some experimental procedures used in determining the extent of lipidogenesis in man. The questions raised are fully discussed. Their solution is sought via an experiment on the rat involving the comparison of tissue and plasma lipid metabolites values following infusion of a labelled glucose bolus. Little correlation was noted, low plasma levels being found with high tissue radioactivity. It is emphasized that it is very difficult to ideate a valid experimental approach in order to investigate the extent of lipidogenesis in man in vivo: in this respect, the long term risk arising from the use of tracers with a very long half-life (e.g. 14C) in man must be carefully valuated. | [
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|
PMID:16583 | Survival test of submersible life support systems. | An experiment to validate predictions concerning submersible survivability was performed in December, 1975, by members of the Canadian Forces in the CF Submersible Lockout Vehicle SDL-1 in Halifax Harbour in water of 4 degrees C temperature at a depth of 40 ft. Data was collected relevant to the life support equipment to determine if it would operate for a simulated 6-h mission followed by a 24-h immobility period, at the end of which rescue was presumed to have occurred. Physiological data was collected from the submersible occupants in order to assess the degree of thermal stress experienced in this exercise. The experiment was terminated after a duration of approximately 25 h at 1 atm internal pressure due to exhaustion of two of the three on-board power supplies, causing the CO2 scrubbers to be inoperative and the CO2 content in the breathing gas to increase to toxic levels. Only two of the three submersible occupants experienced cold stress, one in the forward sphere and one in the aft sphere. At the end of 24 h, the core temperatures of both individuals had decreased by 0.5 degrees C and, during this time, skin temperatures, particularly of the extremities, had steadily and slowly decreased. Neither individual was hypothermic, but it was considered likely that after a 3-d exposure, at least two of the crew members would have had core temperatures of 35 degrees C or lower, assuming that CO2 poisoning had not occurred earlier. | Survival test of submersible life support systems. An experiment to validate predictions concerning submersible survivability was performed in December, 1975, by members of the Canadian Forces in the CF Submersible Lockout Vehicle SDL-1 in Halifax Harbour in water of 4 degrees C temperature at a depth of 40 ft. Data was collected relevant to the life support equipment to determine if it would operate for a simulated 6-h mission followed by a 24-h immobility period, at the end of which rescue was presumed to have occurred. Physiological data was collected from the submersible occupants in order to assess the degree of thermal stress experienced in this exercise. The experiment was terminated after a duration of approximately 25 h at 1 atm internal pressure due to exhaustion of two of the three on-board power supplies, causing the CO2 scrubbers to be inoperative and the CO2 content in the breathing gas to increase to toxic levels. Only two of the three submersible occupants experienced cold stress, one in the forward sphere and one in the aft sphere. At the end of 24 h, the core temperatures of both individuals had decreased by 0.5 degrees C and, during this time, skin temperatures, particularly of the extremities, had steadily and slowly decreased. Neither individual was hypothermic, but it was considered likely that after a 3-d exposure, at least two of the crew members would have had core temperatures of 35 degrees C or lower, assuming that CO2 poisoning had not occurred earlier. | [
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|
PMID:16584 | Systematic desensitization of a phobia for flying with the use of suggestion. | This case study describes the successful treatment of a phobia for flying in an active-duty United States Marine helicopter crew chief by using systematic desensitization. Systematic desensitization is briefly described as a treatment technique which incorporates relaxation exercises paired with the visualization of anxiety-producing images--in this case, images associated with flying. The patient and the therapist constructed a hierarchy of 32 items which were then rank ordered from least to most anxiety producing with the first item being "Ordering parts to repair a helicopter" and the last item being "A routine helicopter landing". Treatment consisted of having the patient visualize the scenes from the list while achieving a state of deep relaxation. The patient was unique in that he possessed an extraordinary ability to experience olfactory, tactile, auditory, and kinesthetic cues as well as vivid visualizations when imagining the items. The patient moved to the next item on the list only after he could feel relaxed while visualizing the previously anxiety-arousing scene of the preceding item. After progressing through the entire list, the patient initiated an actual helicopter flight. The patient participated in a 6-month follow-up helicopter flight with the therapist and experienced an appropriate, manageable level of anxiety. The presentation concludes with a brief discussion concerning the protential usefulness of routinely incorporating relaxation exercises into flight training as a preventative approach to anxiety- and stress-related illness frequently found in aviators. | Systematic desensitization of a phobia for flying with the use of suggestion. This case study describes the successful treatment of a phobia for flying in an active-duty United States Marine helicopter crew chief by using systematic desensitization. Systematic desensitization is briefly described as a treatment technique which incorporates relaxation exercises paired with the visualization of anxiety-producing images--in this case, images associated with flying. The patient and the therapist constructed a hierarchy of 32 items which were then rank ordered from least to most anxiety producing with the first item being "Ordering parts to repair a helicopter" and the last item being "A routine helicopter landing". Treatment consisted of having the patient visualize the scenes from the list while achieving a state of deep relaxation. The patient was unique in that he possessed an extraordinary ability to experience olfactory, tactile, auditory, and kinesthetic cues as well as vivid visualizations when imagining the items. The patient moved to the next item on the list only after he could feel relaxed while visualizing the previously anxiety-arousing scene of the preceding item. After progressing through the entire list, the patient initiated an actual helicopter flight. The patient participated in a 6-month follow-up helicopter flight with the therapist and experienced an appropriate, manageable level of anxiety. The presentation concludes with a brief discussion concerning the protential usefulness of routinely incorporating relaxation exercises into flight training as a preventative approach to anxiety- and stress-related illness frequently found in aviators. | [
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|
PMID:16587 | The intracellular pH and the buffer capacity of the heart. | The intracellular buffering (delta HCO3-/delta pH) in rats is lowest in skeletal muscle, intermediate in the diaphragm and highest in cardiac muscle. In the hypertrophic heart due to aortic constriction or to the Goldblatt mechanism the buffer value increases markedly during the first weeks, but returns to normal or even subnormal values during stable hypertrophy. There is an electrochemical disequilibrium for hydrogen ions caused by an active transport of ions across the cell membrane, which is possibly correlated to the myocardial activity. | The intracellular pH and the buffer capacity of the heart. The intracellular buffering (delta HCO3-/delta pH) in rats is lowest in skeletal muscle, intermediate in the diaphragm and highest in cardiac muscle. In the hypertrophic heart due to aortic constriction or to the Goldblatt mechanism the buffer value increases markedly during the first weeks, but returns to normal or even subnormal values during stable hypertrophy. There is an electrochemical disequilibrium for hydrogen ions caused by an active transport of ions across the cell membrane, which is possibly correlated to the myocardial activity. | [
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|
PMID:16618 | Lymphocytotoxic antibodies. HLA antigen associations, disease associations, and family studies. | Lymphocytotoxic antibodies (LCTAB) were sought in sera of patients with rheumatic diseases and in family members. Patients with SLE and cutaneous necrotizing venulitis and family members of JRA patients had an increased frequency of LCTAB; JRA patients and family members of SLE patients did not. The only association between LCTAB and the HLA phenotype of persons with LCTAB was a decreased frequency of LCTAB in individuals with HLA-B27. | Lymphocytotoxic antibodies. HLA antigen associations, disease associations, and family studies. Lymphocytotoxic antibodies (LCTAB) were sought in sera of patients with rheumatic diseases and in family members. Patients with SLE and cutaneous necrotizing venulitis and family members of JRA patients had an increased frequency of LCTAB; JRA patients and family members of SLE patients did not. The only association between LCTAB and the HLA phenotype of persons with LCTAB was a decreased frequency of LCTAB in individuals with HLA-B27. | [
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|
PMID:16619 | Determination of flunitrazepam, desmethylflunitrazepam and clonazepam in plasma by gas liquid chromatography with an internal standard. | A method is developed for gas-chromatographic determination of flunitrazepam, desmethylflunitrazepam and clonazepam in plasma, using methylclonazepam as internal standard. Following extraction of the benzodiazepines and their hydrolysis, the benzophenones are analyzed by gas-chromatography, with a glass column filled with 3% OV-225 on Gas Chrom Q and a 63Ni electron capture detector. The technique has a good selectivity. Its limit of sensitivity is about 0.5 ng/ml of plasma. It is suitable for investigations on pharmacokinetics and bioavailability as well as for monitoring the correlation between plasma level and therapeutic efficacy and toxicology. | Determination of flunitrazepam, desmethylflunitrazepam and clonazepam in plasma by gas liquid chromatography with an internal standard. A method is developed for gas-chromatographic determination of flunitrazepam, desmethylflunitrazepam and clonazepam in plasma, using methylclonazepam as internal standard. Following extraction of the benzodiazepines and their hydrolysis, the benzophenones are analyzed by gas-chromatography, with a glass column filled with 3% OV-225 on Gas Chrom Q and a 63Ni electron capture detector. The technique has a good selectivity. Its limit of sensitivity is about 0.5 ng/ml of plasma. It is suitable for investigations on pharmacokinetics and bioavailability as well as for monitoring the correlation between plasma level and therapeutic efficacy and toxicology. | [
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|
PMID:16620 | [Studies on the reactability of chlordiazepoxide to its N-nitrosos derivative in physiological conditions (author's transl)]. | It is shown that chlordiazepoxide readily reacts with sodium nitrite in an aqueous HCl solution as well as in human gastric juice to N-nitrosochlordiazepoxide with a high yield (up to 75%). For this reaction the pH optimum has been determined to be 1.4. After oral application of chlordiazepoxide alone or in combination with nitrite to rats, the drug as well as its N-nitroso derivative were recovered from serum and analysed by high-pressure liquid chromatography. | [Studies on the reactability of chlordiazepoxide to its N-nitrosos derivative in physiological conditions (author's transl)]. It is shown that chlordiazepoxide readily reacts with sodium nitrite in an aqueous HCl solution as well as in human gastric juice to N-nitrosochlordiazepoxide with a high yield (up to 75%). For this reaction the pH optimum has been determined to be 1.4. After oral application of chlordiazepoxide alone or in combination with nitrite to rats, the drug as well as its N-nitroso derivative were recovered from serum and analysed by high-pressure liquid chromatography. | [
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|
PMID:16621 | Serum gonadotropins in the rat after prenatal damage to the testes by busulfan and their reaction to cryptorchidism, castration and administration of testosterone. | Adult male rats prenatally treated with 1,4-bis-(methanesulfonyloxy)-butane (busulfan), which damages the gonocytes, undergo cryptorchidization, castration or testosterone treatment and the FSH, LH and testosterone levels in serum are measured. Basal values of these hormones do not differ from those of controls. After cryptorchidization FSH levels rise but the LH levels do not. Following orchidectomy both hormone levels increase significantly. Application of testosterone in various doses increases FSH in normal animals but not in busulfan treated rats 24 h post infectionem. FSH and LH levels 7 days after administration do not differ from controls. According to the hypothesis that the FSH release depends on an inhibin from the testes, these experiments show evidence for inhibin being produced only in the Sertoli cells. | Serum gonadotropins in the rat after prenatal damage to the testes by busulfan and their reaction to cryptorchidism, castration and administration of testosterone. Adult male rats prenatally treated with 1,4-bis-(methanesulfonyloxy)-butane (busulfan), which damages the gonocytes, undergo cryptorchidization, castration or testosterone treatment and the FSH, LH and testosterone levels in serum are measured. Basal values of these hormones do not differ from those of controls. After cryptorchidization FSH levels rise but the LH levels do not. Following orchidectomy both hormone levels increase significantly. Application of testosterone in various doses increases FSH in normal animals but not in busulfan treated rats 24 h post infectionem. FSH and LH levels 7 days after administration do not differ from controls. According to the hypothesis that the FSH release depends on an inhibin from the testes, these experiments show evidence for inhibin being produced only in the Sertoli cells. | [
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PMID:16622 | Double-blind cross-over clinical comparison of two 2'-chloro benzodiazepines: 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (chlordesmethyldiazepam) versus 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) in neurotic anxiety. | A group of 20 female neurotic inpatients has been treated with 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one-(chlordesmethyldiazepan)- 7-chloro-5(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) according to a double-blind cross-over design. For each drug clinical evaluations were performed by means of Hamilton's rating scale for anxiety states and of Overall and Gorham's brief psychiatric rating scale, at the beginning, after the first week and at the end of the two-week period of treatment, in opposite sequence. A statistically greater efficacy of chlordesmethyldiazepam in comparison to lorazepam was observed. Results are discussed with regard to benzodiazepine structure-activity relationships. | Double-blind cross-over clinical comparison of two 2'-chloro benzodiazepines: 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (chlordesmethyldiazepam) versus 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) in neurotic anxiety. A group of 20 female neurotic inpatients has been treated with 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one-(chlordesmethyldiazepan)- 7-chloro-5(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) according to a double-blind cross-over design. For each drug clinical evaluations were performed by means of Hamilton's rating scale for anxiety states and of Overall and Gorham's brief psychiatric rating scale, at the beginning, after the first week and at the end of the two-week period of treatment, in opposite sequence. A statistically greater efficacy of chlordesmethyldiazepam in comparison to lorazepam was observed. Results are discussed with regard to benzodiazepine structure-activity relationships. | [
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|
PMID:16623 | [Psychic drugs: predicting therapeutic effects and doses by test models with normal subjects (author's transl)]. | Pharmacopsychology is concerned with the effects of drugs on "psychic" processes. It is attempted to demonstrate approaches which meet the criteria of scientific methodology. These approaches are based upon observation of somatic and/or behavioral changes. The steps from "naive" observation to the generation of objective data consist mainly of strict control of the observational situation and of technical refinement of the observation methods. Two kinds of pharmacopsychological models in healthy volunteers are described: models of normal and models of abnormal behaviour. Their relevance for the prediction of therapeutic drug effects and dosage is discussed. Possible new approaches are demonstrated: a) utilization of feedback form clinical investigation to control the relevance of pharmacopsychological models and, b) the concept of symptomatic volunteers, who are shown to be more suitable models than non-selected subjects. | [Psychic drugs: predicting therapeutic effects and doses by test models with normal subjects (author's transl)]. Pharmacopsychology is concerned with the effects of drugs on "psychic" processes. It is attempted to demonstrate approaches which meet the criteria of scientific methodology. These approaches are based upon observation of somatic and/or behavioral changes. The steps from "naive" observation to the generation of objective data consist mainly of strict control of the observational situation and of technical refinement of the observation methods. Two kinds of pharmacopsychological models in healthy volunteers are described: models of normal and models of abnormal behaviour. Their relevance for the prediction of therapeutic drug effects and dosage is discussed. Possible new approaches are demonstrated: a) utilization of feedback form clinical investigation to control the relevance of pharmacopsychological models and, b) the concept of symptomatic volunteers, who are shown to be more suitable models than non-selected subjects. | [
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|
PMID:16624 | Destruction of endogenous low density lipoprotein in incubated intima. | The effect of incubation on the content of endogenous intact plasma lipoprotein (LP) has been examined in minced samples of normal intima and lesions from 38 patients. Both the electrophoretically mobile and the immobilized LP fractions decreased on incubation, and the rate of destruction was proportional to LP concentration (r=0.832, p less than 0.001). Mincing the intima with EDTA before incubation increased the rate of destruction about 4-fold in fibrous lesions but not in lesions containing numerous fat-filled cells. The destruction of LP was highly dependent on pH; the rate was highest below pH 5.5 and destruction was almost completely inhibited above pH 6.4. In standard cathepsin assays haemoglobin substrate was hydrolysed at a rate comparable to the rate of destruction of LP. The results suggest that LP may be degraded by a lysosomal cathepsin in intima. | Destruction of endogenous low density lipoprotein in incubated intima. The effect of incubation on the content of endogenous intact plasma lipoprotein (LP) has been examined in minced samples of normal intima and lesions from 38 patients. Both the electrophoretically mobile and the immobilized LP fractions decreased on incubation, and the rate of destruction was proportional to LP concentration (r=0.832, p less than 0.001). Mincing the intima with EDTA before incubation increased the rate of destruction about 4-fold in fibrous lesions but not in lesions containing numerous fat-filled cells. The destruction of LP was highly dependent on pH; the rate was highest below pH 5.5 and destruction was almost completely inhibited above pH 6.4. In standard cathepsin assays haemoglobin substrate was hydrolysed at a rate comparable to the rate of destruction of LP. The results suggest that LP may be degraded by a lysosomal cathepsin in intima. | [
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PMID:16625 | Effect of prostaglandins E1 and F1alpha on the activities of cholesteryl ester synthetase and cholesteryl ester hydrolases of pigeon aorta in vitro. | The in vitro effects of prostaglandins E1 and F1alpha on the activity of cholesteryl ester synthetase and cholesteryl ester hydrolase activities of the pigeon aorta were examined. It was found that prostaglandin E1 markedly inhibited the cholesteryl ester hydrolase activity in the supernatant fraction and slightly inhibited the cholesteryl ester synthetase activity. Prostaglandin F1alpha, however, modestly stimulated the cholesteryl ester hydrolase activity both in the microsomal and in the supernatant fraction of the aorta. These observations strongly warrant further studies on the role of prostaglandins in atherogenesis. | Effect of prostaglandins E1 and F1alpha on the activities of cholesteryl ester synthetase and cholesteryl ester hydrolases of pigeon aorta in vitro. The in vitro effects of prostaglandins E1 and F1alpha on the activity of cholesteryl ester synthetase and cholesteryl ester hydrolase activities of the pigeon aorta were examined. It was found that prostaglandin E1 markedly inhibited the cholesteryl ester hydrolase activity in the supernatant fraction and slightly inhibited the cholesteryl ester synthetase activity. Prostaglandin F1alpha, however, modestly stimulated the cholesteryl ester hydrolase activity both in the microsomal and in the supernatant fraction of the aorta. These observations strongly warrant further studies on the role of prostaglandins in atherogenesis. | [
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|
PMID:16632 | Comparative beta-adrenoceptor blocking effects and pharmacokinetics of penbutolol and propranolol in man. | 1 The beta-adrenoceptor blocking effects of penbutolol were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 7 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and plasma levels of penbutolol and propranolol were determined. 3 Penbutolol proved to be a non-cardioselective beta-adrenoceptor blocking drug, antagonizing exercise-induced tachycardia, reducing exercise-induced increase in PEFR and decreasing PRA. The beta-adrenolytic potency of penbutolol was shown to be four-fold that of propranolol but the duration of its effect was similar. 4 The peak plasma level of penbutolol was reached 1 h after administration and its half-life was 4.5 h. 5 Comparison of plasma levels and biological activity of penbutolol revealed that after oral administration this drug is transformed into an active metabolite in man. | Comparative beta-adrenoceptor blocking effects and pharmacokinetics of penbutolol and propranolol in man. 1 The beta-adrenoceptor blocking effects of penbutolol were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 7 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and plasma levels of penbutolol and propranolol were determined. 3 Penbutolol proved to be a non-cardioselective beta-adrenoceptor blocking drug, antagonizing exercise-induced tachycardia, reducing exercise-induced increase in PEFR and decreasing PRA. The beta-adrenolytic potency of penbutolol was shown to be four-fold that of propranolol but the duration of its effect was similar. 4 The peak plasma level of penbutolol was reached 1 h after administration and its half-life was 4.5 h. 5 Comparison of plasma levels and biological activity of penbutolol revealed that after oral administration this drug is transformed into an active metabolite in man. | [
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PMID:16633 | Measurement of thioridazine in blood and urine. | 1 Thioridazine can be specifically, simply, and reliably measured in plasma and urine by gas chromatography using hexane extraction and prochlorperazine as internal standard; fluorimetry is non-specific. 2 The method can also measure thioridazine ring sulphoxide, and mesoridazine-plus-sulphoridazine (M/S). 3 After single doses plasma sometimes shows M/S in addition to thioridazine itself; it always does so on continued treatment. There is great individual variation in both components, and evidence of changes in metabolism during the early weeks. 4 Urinary excretion may be influenced by pH, but between pH 6.0-7.0 about 1% of the daily dose appears in 24 h urine as the following: free thioridazine in microng quantities, M/S and ring sulphoxide each in mg amounts. 5 Patients attain steady state conditions, although plasma levels rise considerably after each dose and settle again in about 10 h. After chronic treatment is stopped to half-life is at about 30 h. 6 Plasma levels cannot be related to therapeutic response when this is slow, as in schizophrenia, but interpretations are complicated by the production of clinically active metabolites, and by plasma protein binding. | Measurement of thioridazine in blood and urine. 1 Thioridazine can be specifically, simply, and reliably measured in plasma and urine by gas chromatography using hexane extraction and prochlorperazine as internal standard; fluorimetry is non-specific. 2 The method can also measure thioridazine ring sulphoxide, and mesoridazine-plus-sulphoridazine (M/S). 3 After single doses plasma sometimes shows M/S in addition to thioridazine itself; it always does so on continued treatment. There is great individual variation in both components, and evidence of changes in metabolism during the early weeks. 4 Urinary excretion may be influenced by pH, but between pH 6.0-7.0 about 1% of the daily dose appears in 24 h urine as the following: free thioridazine in microng quantities, M/S and ring sulphoxide each in mg amounts. 5 Patients attain steady state conditions, although plasma levels rise considerably after each dose and settle again in about 10 h. After chronic treatment is stopped to half-life is at about 30 h. 6 Plasma levels cannot be related to therapeutic response when this is slow, as in schizophrenia, but interpretations are complicated by the production of clinically active metabolites, and by plasma protein binding. | [
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|
PMID:16634 | The metabolism, distribution and elimination of chlorphentermine in man. | 1 A gas-liquid chromatography procedure for the determination of chlorphentermine (I), N-hydroxychlorphentermine (II) and alpha,alpha-dimethyl-alpha-nitro-beta-(4-chlorophenyl)ethane (IV) in urine has been developed. Also methods are reported to determine conjugated II and the total N-oxidized metabolites of I, i.e. II, conjugated II, alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and IV in urine. 2 The synthesis of alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and its properties are reported. 3 The kinetics of urinary excretion of I and its metabolic products after the oral administration of I to a human subject on separate occasions have been studied. Under normal conditions of urinary pH, metabolism by N-oxidation was the main elimination route of I; acidifying the urine increased the urinary excretion of unchanged I at the expense of the N-oxidized products. 4 The importance of the N-oxidation metabolic route in the distribution of chlorphentermine (I) in man is discussed. | The metabolism, distribution and elimination of chlorphentermine in man. 1 A gas-liquid chromatography procedure for the determination of chlorphentermine (I), N-hydroxychlorphentermine (II) and alpha,alpha-dimethyl-alpha-nitro-beta-(4-chlorophenyl)ethane (IV) in urine has been developed. Also methods are reported to determine conjugated II and the total N-oxidized metabolites of I, i.e. II, conjugated II, alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and IV in urine. 2 The synthesis of alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and its properties are reported. 3 The kinetics of urinary excretion of I and its metabolic products after the oral administration of I to a human subject on separate occasions have been studied. Under normal conditions of urinary pH, metabolism by N-oxidation was the main elimination route of I; acidifying the urine increased the urinary excretion of unchanged I at the expense of the N-oxidized products. 4 The importance of the N-oxidation metabolic route in the distribution of chlorphentermine (I) in man is discussed. | [
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|
PMID:16635 | A repeated dose comparison of dichloralphenazone, flunitrazepam and amylobarbitone sodium on some aspects of sleep and early morning behaviour in normal subjects. | 1 Seven normal subjects were given three different hypnotics (flunitrazepam 1 mg, amylobarbitone sodium 100 mg and dichloralphenazone 1300 mg) for four consecutive nights each. 2 All three substances improved subjective assessment of the ease of getting to sleep. Flunitrazepam was rated as better than eithr dichloralphenazone or amylobarbitone sodium in this respect. 3 The perceived quality of induced sleep was not altered by any of the preparations. 4 There was a disturbance of the subjective ratings of getting to sleep following cessation of treatment with dichloralphenazone, giving tentative support to the existence of a 'rebound' effect. 5 Dichloralphenazone produced an impairment in psychomotor performance as measured on a complex reaction time test following four nights medication with the drug. | A repeated dose comparison of dichloralphenazone, flunitrazepam and amylobarbitone sodium on some aspects of sleep and early morning behaviour in normal subjects. 1 Seven normal subjects were given three different hypnotics (flunitrazepam 1 mg, amylobarbitone sodium 100 mg and dichloralphenazone 1300 mg) for four consecutive nights each. 2 All three substances improved subjective assessment of the ease of getting to sleep. Flunitrazepam was rated as better than eithr dichloralphenazone or amylobarbitone sodium in this respect. 3 The perceived quality of induced sleep was not altered by any of the preparations. 4 There was a disturbance of the subjective ratings of getting to sleep following cessation of treatment with dichloralphenazone, giving tentative support to the existence of a 'rebound' effect. 5 Dichloralphenazone produced an impairment in psychomotor performance as measured on a complex reaction time test following four nights medication with the drug. | [
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PMID:16637 | Localized scleroderma-like lesions after bone marrow transplantation in man. A chronic graft versus host reaction. | Localized scleroderma-like skin lesions which developed in two children, from 8 to 10 months after successful bone marrow transplantation for aplastic anaemia, showed histopathological features resembling those of scleroderma. This finding, like the animal models described in the literature, provides additional support for the auto-immune nature of scleroderma. | Localized scleroderma-like lesions after bone marrow transplantation in man. A chronic graft versus host reaction. Localized scleroderma-like skin lesions which developed in two children, from 8 to 10 months after successful bone marrow transplantation for aplastic anaemia, showed histopathological features resembling those of scleroderma. This finding, like the animal models described in the literature, provides additional support for the auto-immune nature of scleroderma. | [
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PMID:16638 | Proton nuclear magnetic resonance study of the effect of pH on tRNA structure. | The low-field 220-MHz proton nuclear magnetic resonance (NMR) spectra of four tRNA molecules, Escherichia coli tRNAPhe, tRNA1Val, and tRNAfMet1, and yeast tRNAPhe, at neutral and mildly acidic pH are compared. We find a net increase in the number of resonances contributing to the -9.9-ppm peak (downfield from sodium 4,4-dimethyl-4-silapentanesulfonate) in three of these tRNAs at pH 6, while tRNAfMet1 does not clearly exhibit this behavior. The increase in intensity at this resonance position is half-completed at pH 6.2 in the case of yeast tRNAPhe. An alteration at the 5'-phosphate terminus is not involved, since removal of the terminal phosphate does not affect the gain in intensity at -9.9 ppm. Based on a survey of the tertiary interactions in the four molecules, assuming that they possess tertiary structures like that of yeast tRNAPhe at neutral pH, we tentatively attribute this altered resonance in E. coli and yeast tRNAPhe to the protonation of the N3 of the adenine residue at position 9 which results in the stabilization of the tertiary triple A23-U12-A9. This intepretation is supported by model studies on the lowfield proton NMR spectrum of AN oligomers at acid pH, which reveal an exchanging proton resonance at -9.4 ppm if the chain length N greater than or equal to 6. | Proton nuclear magnetic resonance study of the effect of pH on tRNA structure. The low-field 220-MHz proton nuclear magnetic resonance (NMR) spectra of four tRNA molecules, Escherichia coli tRNAPhe, tRNA1Val, and tRNAfMet1, and yeast tRNAPhe, at neutral and mildly acidic pH are compared. We find a net increase in the number of resonances contributing to the -9.9-ppm peak (downfield from sodium 4,4-dimethyl-4-silapentanesulfonate) in three of these tRNAs at pH 6, while tRNAfMet1 does not clearly exhibit this behavior. The increase in intensity at this resonance position is half-completed at pH 6.2 in the case of yeast tRNAPhe. An alteration at the 5'-phosphate terminus is not involved, since removal of the terminal phosphate does not affect the gain in intensity at -9.9 ppm. Based on a survey of the tertiary interactions in the four molecules, assuming that they possess tertiary structures like that of yeast tRNAPhe at neutral pH, we tentatively attribute this altered resonance in E. coli and yeast tRNAPhe to the protonation of the N3 of the adenine residue at position 9 which results in the stabilization of the tertiary triple A23-U12-A9. This intepretation is supported by model studies on the lowfield proton NMR spectrum of AN oligomers at acid pH, which reveal an exchanging proton resonance at -9.4 ppm if the chain length N greater than or equal to 6. | [
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|
PMID:16639 | Sodium-dependent methyl 1-thio-beta-D-galactopyranoside transport in membrane vesicles isolated from Salmonella typhimurium. | Membrane vesicles isolated from Salmonella typhimurium G-30 grown in the presence of melibiose catalyze methyl 1-thio-beta-D-galactopyranoside (TMG) transport in the presence of sodium or lithium, as shown initially with intact cells by Stock and Roseman (Stock, J., and Roseman, S. (1971), Biochem. Biophys. Res. Commun. 44, 132). TMG-dependent sodium uptake is also observed, but only when a potassium diffusion potential (interior negative) is induced across the vesicle membrane. Cation-dependent TMG accumulation varies with the electrochemical gradient of protons generated as a result of D-lactate oxidation, and the vesicles catalyze D-lactate-dependent sodium efflux in a manner which is consistent with the operation of a proton-sodium exchange mechanism. Although the stoichiometry between sodium and TMG appears to be 1:1 when transport is induced by a potassium diffusion potential, evidence is presented which indicates that the relationship may exceed unity under certain conditions. The results are explained in terms of a model in which TMG-sodium (lithium) symport is driven by an electrochemical gradient of protons which functions to maintain a low intravesicular sodium or lithium concentration through proton--sodium (lithium) antiport. | Sodium-dependent methyl 1-thio-beta-D-galactopyranoside transport in membrane vesicles isolated from Salmonella typhimurium. Membrane vesicles isolated from Salmonella typhimurium G-30 grown in the presence of melibiose catalyze methyl 1-thio-beta-D-galactopyranoside (TMG) transport in the presence of sodium or lithium, as shown initially with intact cells by Stock and Roseman (Stock, J., and Roseman, S. (1971), Biochem. Biophys. Res. Commun. 44, 132). TMG-dependent sodium uptake is also observed, but only when a potassium diffusion potential (interior negative) is induced across the vesicle membrane. Cation-dependent TMG accumulation varies with the electrochemical gradient of protons generated as a result of D-lactate oxidation, and the vesicles catalyze D-lactate-dependent sodium efflux in a manner which is consistent with the operation of a proton-sodium exchange mechanism. Although the stoichiometry between sodium and TMG appears to be 1:1 when transport is induced by a potassium diffusion potential, evidence is presented which indicates that the relationship may exceed unity under certain conditions. The results are explained in terms of a model in which TMG-sodium (lithium) symport is driven by an electrochemical gradient of protons which functions to maintain a low intravesicular sodium or lithium concentration through proton--sodium (lithium) antiport. | [
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PMID:16640 | Determination of the rate-limiting steps and chemical mechanism of fructokinase by isotope exchange, isotope partitioning, and pH studies. | Isotope exchange studies show that beef liver fructokinase has a random kinetic mechanism in which release of fructose from the enzyme is slower than that catalytic reaction. The stickiness of fructose in the presence of MgATP is confirmed by isotope partition studies, which show it to be released 0.53 times as fast as V1/Et in the presence, and 80--130 times as fast in the absence of MgATP. Fructose-1-P release from it binary complex is not at all rate limiting in the forward direction since no exchange of MgADP back into MgATP could be observed during the forward reaction. Failure to find any isotope effect by the equilibrium perturbation method with [1-18O]fructose (upper limit, 1.003, shows that P--O bond cleavage or formation is not rate limiting. The pH profiles for the forward reaction show a group (probably carboxyl with pK 5.7-6.0 and deltaHion = 0) that must be ionized and a group (perhaps lysine, with pK 9--10, and deltaHion 5-9 kcal/mol) which must be protonated for activity. The profile for the back reaction shows only a group with pK 5.5--6 that must be protonated for activity. A chemical mechanism is proposed in which a carboxyl group on the enzyme accepts a proton from the 1-hydroxyl of fructose during the forward reaction and donates it back during the reverse reaction. | Determination of the rate-limiting steps and chemical mechanism of fructokinase by isotope exchange, isotope partitioning, and pH studies. Isotope exchange studies show that beef liver fructokinase has a random kinetic mechanism in which release of fructose from the enzyme is slower than that catalytic reaction. The stickiness of fructose in the presence of MgATP is confirmed by isotope partition studies, which show it to be released 0.53 times as fast as V1/Et in the presence, and 80--130 times as fast in the absence of MgATP. Fructose-1-P release from it binary complex is not at all rate limiting in the forward direction since no exchange of MgADP back into MgATP could be observed during the forward reaction. Failure to find any isotope effect by the equilibrium perturbation method with [1-18O]fructose (upper limit, 1.003, shows that P--O bond cleavage or formation is not rate limiting. The pH profiles for the forward reaction show a group (probably carboxyl with pK 5.7-6.0 and deltaHion = 0) that must be ionized and a group (perhaps lysine, with pK 9--10, and deltaHion 5-9 kcal/mol) which must be protonated for activity. The profile for the back reaction shows only a group with pK 5.5--6 that must be protonated for activity. A chemical mechanism is proposed in which a carboxyl group on the enzyme accepts a proton from the 1-hydroxyl of fructose during the forward reaction and donates it back during the reverse reaction. | [
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|
PMID:16641 | Carbon-13 nuclear magnetic resonance probe of active-site ionizations in human carbonic anhydrase B. | Human carbonic anhydrase B (HCAB), prepared by a new affinity chromatography procedure, was carboxymethylated exclusively at NT of its active-site histidine-200 using 90% [1-13C]bromoacetate. The 13C nuclear magnetic resonance signal of the covalently attached carboxylate was easily detected over the natural abundance background due to the other carbonyl and carboxyl carbons of this 29 000 molecular weight zinc metalloenzyme. Its chemical shift proved very sensitive to the presence of inhibitors in the active site and to variations in pH. Two perturbing groups with pKa values of 6.0 and 9.2 were assigned to the modified histidine-200 itself and the zinc-bound water ligand, respectively, making use of 13C NMR titration data on Nr- and Nr-carboxymethyl-L-histidine model compounds. The results rule out histidine-200 as the critical group whose ionization controls the catalytic activity. They also strongly suggest an interaction of the carboxylate of the carboxymethyl group with either the zinc or its water ligand around pH 8, possibly explaining the basis for the major differences between HCAB and CmHCAB. | Carbon-13 nuclear magnetic resonance probe of active-site ionizations in human carbonic anhydrase B. Human carbonic anhydrase B (HCAB), prepared by a new affinity chromatography procedure, was carboxymethylated exclusively at NT of its active-site histidine-200 using 90% [1-13C]bromoacetate. The 13C nuclear magnetic resonance signal of the covalently attached carboxylate was easily detected over the natural abundance background due to the other carbonyl and carboxyl carbons of this 29 000 molecular weight zinc metalloenzyme. Its chemical shift proved very sensitive to the presence of inhibitors in the active site and to variations in pH. Two perturbing groups with pKa values of 6.0 and 9.2 were assigned to the modified histidine-200 itself and the zinc-bound water ligand, respectively, making use of 13C NMR titration data on Nr- and Nr-carboxymethyl-L-histidine model compounds. The results rule out histidine-200 as the critical group whose ionization controls the catalytic activity. They also strongly suggest an interaction of the carboxylate of the carboxymethyl group with either the zinc or its water ligand around pH 8, possibly explaining the basis for the major differences between HCAB and CmHCAB. | [
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|
PMID:16642 | Comparison of solubility properties of alpha-paramyosin, beta-paramyosin and acid-extracted paramyosin. | The solubility properties of paramyosin in the zones of pH and ionic strength in which aggregation occurs were initially studied using preparations isolated by a method originally described by Bailey (Bailey, K. (1956), Pubbl. Stn. Zool. Napoli 29, 26). Other preparations yielding apparently different protein components have been described by Hodge (Hodge, A.J. (1952), Proc. Natl. Acad. Sci., U.S.A. 38, 850) using acid conditions, and Stafford and Yphantis (Stafford, W.F., AND Yphantis, D. (1972), Biochem. Biophys. Res. Commun. 49, 848) have identified alpha-, beta-, and gamma-paramyosin using various times and temperatures of extraction with or without ethylenediaminetetraacetic acid. We have found that acid-extracted paramyosin is very similar if not identical to alpha-paramyosin, but that both acid and alpha forms differ considerably from beta- and gamma-paramyosin. Beta-Paramyosin precipitates abruptly from solution in narrow zone of pH below neutrality, and increases in ionic strength shift the zone of precipitation toward lower pH values. In contrast, both acid and alpha-paramyosin show gradual aggregation with changing pH at lowerionic strength (less than 0.3) but sharp transitions similar to beta-paramyosin at higher ionic strength (greater than 0.3). Transitions were also found at lower pH (ca. 4.0) which were not mirror images of transitions at higher pH (ca. 7.0). Viscosity measurements show that acid extracted paramyosin is close in behavior to a native extract obtained by extraction in mild, nondenaturing media containing mixed antibiotics. Each of these extracts differed considerably from beta-paramyosin. Mild, nonhydrolytic procedures employed by others to remove small, noncovalent bonded components or to separate protein complexes were not effective in converting alpha- to beta-paramyosin. Comparison of extraction procedures strongly supports the suggestion of Stafford and Yphantis that beta- and gamma-paramyosin are hydrolytic products of alpha-paramyosin and that the proteases responsible may be of bacterial origin. | Comparison of solubility properties of alpha-paramyosin, beta-paramyosin and acid-extracted paramyosin. The solubility properties of paramyosin in the zones of pH and ionic strength in which aggregation occurs were initially studied using preparations isolated by a method originally described by Bailey (Bailey, K. (1956), Pubbl. Stn. Zool. Napoli 29, 26). Other preparations yielding apparently different protein components have been described by Hodge (Hodge, A.J. (1952), Proc. Natl. Acad. Sci., U.S.A. 38, 850) using acid conditions, and Stafford and Yphantis (Stafford, W.F., AND Yphantis, D. (1972), Biochem. Biophys. Res. Commun. 49, 848) have identified alpha-, beta-, and gamma-paramyosin using various times and temperatures of extraction with or without ethylenediaminetetraacetic acid. We have found that acid-extracted paramyosin is very similar if not identical to alpha-paramyosin, but that both acid and alpha forms differ considerably from beta- and gamma-paramyosin. Beta-Paramyosin precipitates abruptly from solution in narrow zone of pH below neutrality, and increases in ionic strength shift the zone of precipitation toward lower pH values. In contrast, both acid and alpha-paramyosin show gradual aggregation with changing pH at lowerionic strength (less than 0.3) but sharp transitions similar to beta-paramyosin at higher ionic strength (greater than 0.3). Transitions were also found at lower pH (ca. 4.0) which were not mirror images of transitions at higher pH (ca. 7.0). Viscosity measurements show that acid extracted paramyosin is close in behavior to a native extract obtained by extraction in mild, nondenaturing media containing mixed antibiotics. Each of these extracts differed considerably from beta-paramyosin. Mild, nonhydrolytic procedures employed by others to remove small, noncovalent bonded components or to separate protein complexes were not effective in converting alpha- to beta-paramyosin. Comparison of extraction procedures strongly supports the suggestion of Stafford and Yphantis that beta- and gamma-paramyosin are hydrolytic products of alpha-paramyosin and that the proteases responsible may be of bacterial origin. | [
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PMID:16650 | Cotransport of phosphate and sodium by yeast. | Phosphate uptake by yeast at pH 7.2 is mediated by two mechanisms, one of which has a Km of 30 micronM and is independent of sodium, and a sodium-dependent mechanism with a Km of 0.6 micronM, both Km values with respect to monovalent phosphate. The sodium-dependent mechanism has two sites with affinity for Na+, with affinity constants of 0.04 and 29 mM. Also lithium enhances phosphate uptake; the affinity constants for lithium are 0.3 and 36 mM. Other alkali ions do not stimulate phosphate uptake at pH 7.2. Ribidium has no effect on the stimulation of phosphate uptake by sodium. Phosphate and arsenate enhance sodium uptake at pH 7.2. The Km of this stimulation with regard to monovalent orthophosphate is about equal to that of the sodium-dependent phosphate uptake. The properties of the cation binding sites of the phosphate uptake mechanism and those of the phosphate-dependent cation transport mechanism have been compared. The existence of a separate sodium-phosphate cotransport system is proposed. | Cotransport of phosphate and sodium by yeast. Phosphate uptake by yeast at pH 7.2 is mediated by two mechanisms, one of which has a Km of 30 micronM and is independent of sodium, and a sodium-dependent mechanism with a Km of 0.6 micronM, both Km values with respect to monovalent phosphate. The sodium-dependent mechanism has two sites with affinity for Na+, with affinity constants of 0.04 and 29 mM. Also lithium enhances phosphate uptake; the affinity constants for lithium are 0.3 and 36 mM. Other alkali ions do not stimulate phosphate uptake at pH 7.2. Ribidium has no effect on the stimulation of phosphate uptake by sodium. Phosphate and arsenate enhance sodium uptake at pH 7.2. The Km of this stimulation with regard to monovalent orthophosphate is about equal to that of the sodium-dependent phosphate uptake. The properties of the cation binding sites of the phosphate uptake mechanism and those of the phosphate-dependent cation transport mechanism have been compared. The existence of a separate sodium-phosphate cotransport system is proposed. | [
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|
PMID:16651 | Intracellular distribution of ribonuclease activity during erythroid cell development. | Five ribonuclease activities, separable by polyacrylamide gel electrophoresis, have been detected in erythroid bone marrow cells from anaemic rabbits. Their intracellular distribution has been investigated and compared with that of the ribonucleases in reticulocytes. Both the acid and alkaline ribonuclease activities of reticulocytes are much lower (30--50 fold) than those of bone marrow erythroid cells. The most marked decrease in enzyme activity occurs in the fractions containing ribosomes and mitochondria plus lysosomes. In these subcellular organelles there was also a qualitative change in the ribonuclease electrophoretic pattern, whereas the cytosol enzymes of marrow erythroid cells and reticulocytes remained largely unchanged. Several ribonucleases released from reticulocyte membranes with urea were similar to those present in the lysosomal plus mitochondrial fraction, as shown by detection of enzyme activity after polyacrylamide gel electrophoresis. The decline in ribonuclease activity was found to begin in the orthochromatic cells, which have a highly condensed nucleus and are no longer active in DNA and RNA synthesis, and to coincide with a decrease in acid phosphatase activity and loss of lysosomes. | Intracellular distribution of ribonuclease activity during erythroid cell development. Five ribonuclease activities, separable by polyacrylamide gel electrophoresis, have been detected in erythroid bone marrow cells from anaemic rabbits. Their intracellular distribution has been investigated and compared with that of the ribonucleases in reticulocytes. Both the acid and alkaline ribonuclease activities of reticulocytes are much lower (30--50 fold) than those of bone marrow erythroid cells. The most marked decrease in enzyme activity occurs in the fractions containing ribosomes and mitochondria plus lysosomes. In these subcellular organelles there was also a qualitative change in the ribonuclease electrophoretic pattern, whereas the cytosol enzymes of marrow erythroid cells and reticulocytes remained largely unchanged. Several ribonucleases released from reticulocyte membranes with urea were similar to those present in the lysosomal plus mitochondrial fraction, as shown by detection of enzyme activity after polyacrylamide gel electrophoresis. The decline in ribonuclease activity was found to begin in the orthochromatic cells, which have a highly condensed nucleus and are no longer active in DNA and RNA synthesis, and to coincide with a decrease in acid phosphatase activity and loss of lysosomes. | [
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|
PMID:16652 | The essential activated carboxyl group of inorganic pyrophosphatase. | 1. A carboxyl group of high reactivity has been found in inorganic pyrophosphatase (pyrophosphate phosphohydrolase, EC 3.6.1.1) from yeast. This group interacts with agents which react neither with carboxyl groups of low molecular weight compounds nor with other carboxyl groups of the protein. 2. The reaction of this activated carboxyl group with inorganic phosphate, hydroxylamine, N-methyl- and O-methylhydroxylamines, and glycine methyl ester has been studied. 3. Homoserine and homoserine lactone were found in the hydrolyzate of phosphorylated and NaBH4-reduced pyrophosphatase, indicating that an aspartyl residue is phosphorylated. 4. Hydroxylamine and other nucleophilic agents cause inactivation of pyrophosphatase as a result of interaction with a carboxyl group. Both diaminobutyric and diaminopropionic acids were seen in the acid hydrolyzate of the protein treated with hydroxylamine and subjected to rearrangement in the presence of carbodiimide. 5. The ways in which the activation of a carboxyl group in the enzyme is achieved and the presumed mechanism of action of inorganic pyrophosphatase are discussed. | The essential activated carboxyl group of inorganic pyrophosphatase. 1. A carboxyl group of high reactivity has been found in inorganic pyrophosphatase (pyrophosphate phosphohydrolase, EC 3.6.1.1) from yeast. This group interacts with agents which react neither with carboxyl groups of low molecular weight compounds nor with other carboxyl groups of the protein. 2. The reaction of this activated carboxyl group with inorganic phosphate, hydroxylamine, N-methyl- and O-methylhydroxylamines, and glycine methyl ester has been studied. 3. Homoserine and homoserine lactone were found in the hydrolyzate of phosphorylated and NaBH4-reduced pyrophosphatase, indicating that an aspartyl residue is phosphorylated. 4. Hydroxylamine and other nucleophilic agents cause inactivation of pyrophosphatase as a result of interaction with a carboxyl group. Both diaminobutyric and diaminopropionic acids were seen in the acid hydrolyzate of the protein treated with hydroxylamine and subjected to rearrangement in the presence of carbodiimide. 5. The ways in which the activation of a carboxyl group in the enzyme is achieved and the presumed mechanism of action of inorganic pyrophosphatase are discussed. | [
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|
PMID:16653 | The stereospecificity of nitrate reductase for hydrogen removal from reduced pyridine nucleotides. | The stereospecificity of the hydrogen removal from reduced pyridine nucleotides catalyzed by nitrate reductase (NADH : nitrate oxidoreductase, EC 1.6.6.1, and NAD(P)H : nitrate oxidoreductase, EC 1.6.6.2) was investigated. A high degree of enzyme purification was required to obtain conclusive results. Improvements are described for the purification of nitrate reductase from Chlorella fusca and from spinach (Spinacea oleracea, L.) leaves. The latter enzyme is shown to contain a cytochrome. With highly purified nitrate reductase preparations from Cl. fusca, Neurospora crassa, Rhodotorula glutinis and spinach leaves the stereospecificity of the reaction was determined to be predominantly of the A-type in all cases. | The stereospecificity of nitrate reductase for hydrogen removal from reduced pyridine nucleotides. The stereospecificity of the hydrogen removal from reduced pyridine nucleotides catalyzed by nitrate reductase (NADH : nitrate oxidoreductase, EC 1.6.6.1, and NAD(P)H : nitrate oxidoreductase, EC 1.6.6.2) was investigated. A high degree of enzyme purification was required to obtain conclusive results. Improvements are described for the purification of nitrate reductase from Chlorella fusca and from spinach (Spinacea oleracea, L.) leaves. The latter enzyme is shown to contain a cytochrome. With highly purified nitrate reductase preparations from Cl. fusca, Neurospora crassa, Rhodotorula glutinis and spinach leaves the stereospecificity of the reaction was determined to be predominantly of the A-type in all cases. | [
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|
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