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PMID:8633 | A quantitative study of metiamide, a histamine H2-antagonist, on the isolated whole rat stomach. | 1. An isolated whole stomach preparation from immature rats is described. The lumen of the stomach was perfused and the hydrogen ion activity of the perfusate recorded continuously. 2. The mean basal acid secretion before stimulation was 4-19 +/- 0-31 X 10 (-8) mol min-1. Metiamide did not significantly reduce this spontaneous secretion. 3. The preparation gave dose-dependent responses to histomine (10(-5)-10(-4)M) which were readily reversed on washing. 4. The effect of metiamide on histamine-stimulated acid secretion was investigated. Metamide, at doses of 3 X 10(-6)M, and 3 X 10(-5)M, caused a parallel displacement of the histamine dose-response curve, indicating competitive antagonism. These dose-response curves were used to calculate dose ratios (DR) for metiamide. 5. A plot of log10 (DR - 1) against log 10 [antagonist] gave a pA2 value for metiamide of 5-91. | A quantitative study of metiamide, a histamine H2-antagonist, on the isolated whole rat stomach. 1. An isolated whole stomach preparation from immature rats is described. The lumen of the stomach was perfused and the hydrogen ion activity of the perfusate recorded continuously. 2. The mean basal acid secretion before stimulation was 4-19 +/- 0-31 X 10 (-8) mol min-1. Metiamide did not significantly reduce this spontaneous secretion. 3. The preparation gave dose-dependent responses to histomine (10(-5)-10(-4)M) which were readily reversed on washing. 4. The effect of metiamide on histamine-stimulated acid secretion was investigated. Metamide, at doses of 3 X 10(-6)M, and 3 X 10(-5)M, caused a parallel displacement of the histamine dose-response curve, indicating competitive antagonism. These dose-response curves were used to calculate dose ratios (DR) for metiamide. 5. A plot of log10 (DR - 1) against log 10 [antagonist] gave a pA2 value for metiamide of 5-91. | [
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PMID:8634 | Evidence that brain prostaglandin synthesis is not essential in fever. | 1. We have tested the hypothesis that a fever caused by pyrogen depends upon the synthesis of prostaglandin E in the brain and that the prostaglandin in turn acts on the hypothalamus to produce fever. 2. In rabbits, fever was produced by the injection of leucocyte pyrogen in a lateral cerebral ventricle. The latency, rate of rise and magnitude of the fever was unaffected by the simultaneous intraventricular injection of two prostaglandin antagonists, SC 19220 and HR 546. 3. Both antagonists effectively attenuated the fever caused by the intraventricular injection of prostaglandin E2. 4. This evidence is not consistent with the hypothesis that prostaglandin E is the principal mediator of fever. | Evidence that brain prostaglandin synthesis is not essential in fever. 1. We have tested the hypothesis that a fever caused by pyrogen depends upon the synthesis of prostaglandin E in the brain and that the prostaglandin in turn acts on the hypothalamus to produce fever. 2. In rabbits, fever was produced by the injection of leucocyte pyrogen in a lateral cerebral ventricle. The latency, rate of rise and magnitude of the fever was unaffected by the simultaneous intraventricular injection of two prostaglandin antagonists, SC 19220 and HR 546. 3. Both antagonists effectively attenuated the fever caused by the intraventricular injection of prostaglandin E2. 4. This evidence is not consistent with the hypothesis that prostaglandin E is the principal mediator of fever. | [
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PMID:8636 | Non-uniform probabilities of quantal release at the crayfish neuromuscular junction. | 1. Transmitter release at the neuromuscular junction of the crayfish walking leg has been found to deviate from binomial predictions immediately after the onset of repetitive stimulation of the presynaptic nerve at frequencies of at least 15 Hz. 2. After several minutes of continuous stimulation, and at lower rates of stimulation, however, the number of quanta released could be described quite well by binomial or Poisson statistics. 3. Deviations from the theoretical expectations were characterized by (a) fewer release failures than predicted, (b) occasions in which the number of quanta released was more than the estimated number of quanta available for release, and (c) a tendency for the data to be underdispersed. 4. Each of these three characteristics are consistent with the hypothesis that different releasable quanta may have different probabilities of responding to a nerve impulse. 5. Using two different methods, different values of the non-uniform probabilities were estimated from the data. At each synaptic site at least one of the estimated probabilities was very high. 6. The need for caution in interpreting statistical description of quantal release is emphasized. | Non-uniform probabilities of quantal release at the crayfish neuromuscular junction. 1. Transmitter release at the neuromuscular junction of the crayfish walking leg has been found to deviate from binomial predictions immediately after the onset of repetitive stimulation of the presynaptic nerve at frequencies of at least 15 Hz. 2. After several minutes of continuous stimulation, and at lower rates of stimulation, however, the number of quanta released could be described quite well by binomial or Poisson statistics. 3. Deviations from the theoretical expectations were characterized by (a) fewer release failures than predicted, (b) occasions in which the number of quanta released was more than the estimated number of quanta available for release, and (c) a tendency for the data to be underdispersed. 4. Each of these three characteristics are consistent with the hypothesis that different releasable quanta may have different probabilities of responding to a nerve impulse. 5. Using two different methods, different values of the non-uniform probabilities were estimated from the data. At each synaptic site at least one of the estimated probabilities was very high. 6. The need for caution in interpreting statistical description of quantal release is emphasized. | [
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PMID:8637 | Caudate stimulation and substantia nigra activity in the rat. | 1. The responses of spontaneously active single neurones in the substantia nigra and overlying mesencephalic reticular formation have been analysed during the electrical stimulation of the ipsilateral caudate nucleus. Experiments were performed in rats anaesthetized with urethane or pentobarbitone. All recordings were made extracellularly with multi-barrelled glass micropipettes which were also used to test neuronal responsiveness to electrophoretically administered substances. The micropipette tip position was marked and the distribution of neurones studied has been analysed. 2. Single shock stimulation of the caudate nucleus inhibited neuronal activity in the substantia nigra (270/320 cells: mean latency 5-4 msec) and in the mesencephalic reticular formation (62/72 cells: mean latency 16-6 msec). However, these effects were often accompanied by periods of excitation. In pentobarbitone anaesthetized animals the latency and duration of these substantia nigra inhibitions was increased. 3. Compared with the zona reticulata, fewer neurones in the zona compacta of the substantia nigra responded to caudate stimulation in both urethane or pentobarbitone anaesthetized animals. 4. The activity of most cells was depressed by electrophoretically administered GABA or glycine and increased by acetylcholine or glutamate. Neurones of the mesencephalic reticular formation were less sensitive to GABA and glycine than substantia nigra neurones. Within the substantia nigra, both zona compacta and zona reticulata neurones were more sensitive to GABA than to glycine. Over-all, glutamate was a more potent excitant than acetylcholine (ACh). 5. Electrophoretic bicuculline methochloride (BMC) consistently reduced GABA but not glycine depression of substantia nigra neurones. Approximately twice as much BMC was required to reduce the endogenous inhibition of the same substantia nigra neurones and the amplitude of concomitantly evoked positive field potential as was required to abolish exogenous GABA responses. Some evoked substantia nigra inhibitions were resistant to BMC. 6. Electrophoretic strychnine consistently reduced glycine but not GABA depression of substantia nigra neurones, and did not modify caudate evoked inhibition of these neurones or the accompanying field potential. 7. The results support the concept of a slowly conducting caudato-nigral pathway which has both facilitatory and inhibitory components. The inhibitory pathway uses GABA as the neurotransmitter. The identity of the possible excitatory transmitter is unknown. The monosynaptic nature of this pathway is uncertain and the possible contribution of other bicuculline insensitive nigral inhibitory processes is discussed. | Caudate stimulation and substantia nigra activity in the rat. 1. The responses of spontaneously active single neurones in the substantia nigra and overlying mesencephalic reticular formation have been analysed during the electrical stimulation of the ipsilateral caudate nucleus. Experiments were performed in rats anaesthetized with urethane or pentobarbitone. All recordings were made extracellularly with multi-barrelled glass micropipettes which were also used to test neuronal responsiveness to electrophoretically administered substances. The micropipette tip position was marked and the distribution of neurones studied has been analysed. 2. Single shock stimulation of the caudate nucleus inhibited neuronal activity in the substantia nigra (270/320 cells: mean latency 5-4 msec) and in the mesencephalic reticular formation (62/72 cells: mean latency 16-6 msec). However, these effects were often accompanied by periods of excitation. In pentobarbitone anaesthetized animals the latency and duration of these substantia nigra inhibitions was increased. 3. Compared with the zona reticulata, fewer neurones in the zona compacta of the substantia nigra responded to caudate stimulation in both urethane or pentobarbitone anaesthetized animals. 4. The activity of most cells was depressed by electrophoretically administered GABA or glycine and increased by acetylcholine or glutamate. Neurones of the mesencephalic reticular formation were less sensitive to GABA and glycine than substantia nigra neurones. Within the substantia nigra, both zona compacta and zona reticulata neurones were more sensitive to GABA than to glycine. Over-all, glutamate was a more potent excitant than acetylcholine (ACh). 5. Electrophoretic bicuculline methochloride (BMC) consistently reduced GABA but not glycine depression of substantia nigra neurones. Approximately twice as much BMC was required to reduce the endogenous inhibition of the same substantia nigra neurones and the amplitude of concomitantly evoked positive field potential as was required to abolish exogenous GABA responses. Some evoked substantia nigra inhibitions were resistant to BMC. 6. Electrophoretic strychnine consistently reduced glycine but not GABA depression of substantia nigra neurones, and did not modify caudate evoked inhibition of these neurones or the accompanying field potential. 7. The results support the concept of a slowly conducting caudato-nigral pathway which has both facilitatory and inhibitory components. The inhibitory pathway uses GABA as the neurotransmitter. The identity of the possible excitatory transmitter is unknown. The monosynaptic nature of this pathway is uncertain and the possible contribution of other bicuculline insensitive nigral inhibitory processes is discussed. | [
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PMID:8639 | Eye protection from light radiation. | It appears that green absorptive lenses are highly desirable for the purposes of shielding the eyes against light radiation from molten metal during the casting and soldering procedures. The dental laboratory technicians have experienced no after-images, less eye fatigue, and no adverse symptoms when using these lenses, as were reported previously. The lenses not only effectively protect the eyes from the injurious light wavelengths, but they also provide for enough normal (as well as individually corrected) vision to accomplish any procedure necessary in the dental laboratory. We propose that the green absorptive lenses, with individual corrections if needed, be considered for dental laboratory technicians during dental laboratory procedures when needed, such as during casting and soldering, to protect their eyes from light radiation. | Eye protection from light radiation. It appears that green absorptive lenses are highly desirable for the purposes of shielding the eyes against light radiation from molten metal during the casting and soldering procedures. The dental laboratory technicians have experienced no after-images, less eye fatigue, and no adverse symptoms when using these lenses, as were reported previously. The lenses not only effectively protect the eyes from the injurious light wavelengths, but they also provide for enough normal (as well as individually corrected) vision to accomplish any procedure necessary in the dental laboratory. We propose that the green absorptive lenses, with individual corrections if needed, be considered for dental laboratory technicians during dental laboratory procedures when needed, such as during casting and soldering, to protect their eyes from light radiation. | [
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] |
PMID:8644 | Giant cell arteritis in general practice. | The clinical syndrome of polymyalgia rheumatica is reviewed. The relationship of this disease with temporal arteritis is discussed, and I consider both syndromes have a pathological basis of generalised giant cell arteritis.Seven cases of polymyalgia and four cases of temporal arteritis were recorded during the six-year period (1969-1975) in one general practice.The outlines of management are discussed, with a plea for earlier recognition of the syndromes of polymyalgia rheumatica and temporal arteritis in general practice. | Giant cell arteritis in general practice. The clinical syndrome of polymyalgia rheumatica is reviewed. The relationship of this disease with temporal arteritis is discussed, and I consider both syndromes have a pathological basis of generalised giant cell arteritis.Seven cases of polymyalgia and four cases of temporal arteritis were recorded during the six-year period (1969-1975) in one general practice.The outlines of management are discussed, with a plea for earlier recognition of the syndromes of polymyalgia rheumatica and temporal arteritis in general practice. | [
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PMID:8643 | [Arteriography in polyarteritis nodosa. 15 cases (author's transl)]. | Despite its imperfections, arteriography, when it demonstrates aneurysms, is an important element in diagnosis in all those cases in which histological findings are not definitive. It should be carried out before renal biopsy, given the risk of traumatic rupture of a possible aneurysm. The discovery of isolated distal arterial stenoses is not characteristic, though in the presence of a suggestive clinical picture, amy be considered as an argument in favour of the diagnosis. They occur frequently in the arteries of the digestive tract even in the absence of any abdominal symptoms or signs. Arteriography also has a prognostic value in establishing the extent of arterial lesions and, finally, is useful in the diagnosis of certain complications such as visceral haematomas and digestive haemorrhages. We thus feel that polyarteritis nodosa should be the object of a complete vascular exploration, including aortography with selective renal studies but also coelio-mesenteric opacification. In the light of the clinical context, the distal limb arteries may also be explored. Thus the diagnosis of polyarteritis nodosa is not purely histological but also arteriographic. | [Arteriography in polyarteritis nodosa. 15 cases (author's transl)]. Despite its imperfections, arteriography, when it demonstrates aneurysms, is an important element in diagnosis in all those cases in which histological findings are not definitive. It should be carried out before renal biopsy, given the risk of traumatic rupture of a possible aneurysm. The discovery of isolated distal arterial stenoses is not characteristic, though in the presence of a suggestive clinical picture, amy be considered as an argument in favour of the diagnosis. They occur frequently in the arteries of the digestive tract even in the absence of any abdominal symptoms or signs. Arteriography also has a prognostic value in establishing the extent of arterial lesions and, finally, is useful in the diagnosis of certain complications such as visceral haematomas and digestive haemorrhages. We thus feel that polyarteritis nodosa should be the object of a complete vascular exploration, including aortography with selective renal studies but also coelio-mesenteric opacification. In the light of the clinical context, the distal limb arteries may also be explored. Thus the diagnosis of polyarteritis nodosa is not purely histological but also arteriographic. | [
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PMID:8646 | Bifidobacteria in the intestinal tract of infants: an in-vivo study. | Weekly faecal specimens from 18 babies were examined during the first 8 weeks of life. Eight infants were breast fed, ten were bottle-fed. All suckling infants received supplementary feeds for the first 8 days. A buffer consisting of acetic acid and acetate was demonstrated in the faeces of all the breast-fed infants at some time during the period of examination. This buffer was rarely detected during the 1st week of life when supplementary feeds were given, and buffer already present gradually disappeared with the introduction of mixed feeding. In contrast, at no time was an acetate buffer demonstrated in the faeces of bottle-fed infants. Babies receiving breast milk produced faeces with low pH, high counts of saccharolytic organisms including bifidobacteria and Streptococcus faecium, and low counts of Escherichia coli, bacteroides and clostridia. Bottle-fed infants on the other hand produced faeces with a high pH and high counts of E. coli and putrefactive bacteria, but with low counts of bifidobacteria. | Bifidobacteria in the intestinal tract of infants: an in-vivo study. Weekly faecal specimens from 18 babies were examined during the first 8 weeks of life. Eight infants were breast fed, ten were bottle-fed. All suckling infants received supplementary feeds for the first 8 days. A buffer consisting of acetic acid and acetate was demonstrated in the faeces of all the breast-fed infants at some time during the period of examination. This buffer was rarely detected during the 1st week of life when supplementary feeds were given, and buffer already present gradually disappeared with the introduction of mixed feeding. In contrast, at no time was an acetate buffer demonstrated in the faeces of bottle-fed infants. Babies receiving breast milk produced faeces with low pH, high counts of saccharolytic organisms including bifidobacteria and Streptococcus faecium, and low counts of Escherichia coli, bacteroides and clostridia. Bottle-fed infants on the other hand produced faeces with a high pH and high counts of E. coli and putrefactive bacteria, but with low counts of bifidobacteria. | [
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PMID:8647 | Bifidobacteria in the intestinal tract of infants: an in-vitro study. | In-vitro studies showed that a number of factors are likely to influence the production and maintenance of a bifidobacillary flora and low pH in the faeces of newborn infants. Considerable importance is attached to the nature of the end products of bacterial metabolism in the large intestine. Thus, there is evidence to suggest that acetic acid and other metabolites of intraluminal bacterial growth suppress the growth of gram-negative organisms, but are without effect upon that of bifidobacteria. This mechanism in turn is controlled by the nature of the feed; important factors in breast milk include high lactose, low protein and low phosphate content. | Bifidobacteria in the intestinal tract of infants: an in-vitro study. In-vitro studies showed that a number of factors are likely to influence the production and maintenance of a bifidobacillary flora and low pH in the faeces of newborn infants. Considerable importance is attached to the nature of the end products of bacterial metabolism in the large intestine. Thus, there is evidence to suggest that acetic acid and other metabolites of intraluminal bacterial growth suppress the growth of gram-negative organisms, but are without effect upon that of bifidobacteria. This mechanism in turn is controlled by the nature of the feed; important factors in breast milk include high lactose, low protein and low phosphate content. | [
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PMID:8649 | Post-traumatic hepatic dysfunction as a major etiology in post-traumatic jaundice. | Thirty-eight patients who had sustained acute trauma, profound hemorrhagic shock, and massive transfusion were studied prospectively to determine the predominant etiologic factors in the development of post-traumatic jaundice. An analysis of clinical and biochemical factors occurring in association with each bilirubin peak in the postoperative course found the jaundice related to transfusion and surgery in 11 instances, to sepsis and septicemia in 15 instances, and to hepatic dysfunction in 23 instances. Results indicated that admission estimates of SGOT and LDH levels, the height of the bilirubin peak and the postoperative day on which it occurs, and the white cell count and GGT at the time of the peak may be of use in the differential diagnosis. Four case reports were used to emphasize the fluctuating pattern of jaundice and the different etiologic factors that may predominate. Light and electron microscopy from three patients illustrated the structural alterations that accompany the biochemical impairment of liver function and enable a more precise appreciation of this syndrome. Hepatic dysfunction appears to be implicated in a high proportion of patients who develop post-traumatic jaundice, which frequently occurs as part of a spectrum of multiple organ failure. | Post-traumatic hepatic dysfunction as a major etiology in post-traumatic jaundice. Thirty-eight patients who had sustained acute trauma, profound hemorrhagic shock, and massive transfusion were studied prospectively to determine the predominant etiologic factors in the development of post-traumatic jaundice. An analysis of clinical and biochemical factors occurring in association with each bilirubin peak in the postoperative course found the jaundice related to transfusion and surgery in 11 instances, to sepsis and septicemia in 15 instances, and to hepatic dysfunction in 23 instances. Results indicated that admission estimates of SGOT and LDH levels, the height of the bilirubin peak and the postoperative day on which it occurs, and the white cell count and GGT at the time of the peak may be of use in the differential diagnosis. Four case reports were used to emphasize the fluctuating pattern of jaundice and the different etiologic factors that may predominate. Light and electron microscopy from three patients illustrated the structural alterations that accompany the biochemical impairment of liver function and enable a more precise appreciation of this syndrome. Hepatic dysfunction appears to be implicated in a high proportion of patients who develop post-traumatic jaundice, which frequently occurs as part of a spectrum of multiple organ failure. | [
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PMID:8650 | Bacterial infection and the asplenic host: a review. | The risk of bacterial sepsis in the surgically or functionally asplenic host is reviewed. The lowest morbidity occurs in patients splenectomized because of trauma to the spleen; the highest morbidity occurs in patients splenectomized for thalassemia. There is approximately a 50% mortality associated with sepsis secondary to asplenia and the pneumococcus is responsible for over 50% of the cases. Normal spleen function and alteration in host defense occurring as a consequence of asplenia is discussed. Finally, alternatives to and indications for splenectomy as well as prophylactic measures are considered. It is concluded that, at the present time, antibiotic coverage for an indefinite period of time may be indicated for surgically or functionally asplenic patients. | Bacterial infection and the asplenic host: a review. The risk of bacterial sepsis in the surgically or functionally asplenic host is reviewed. The lowest morbidity occurs in patients splenectomized because of trauma to the spleen; the highest morbidity occurs in patients splenectomized for thalassemia. There is approximately a 50% mortality associated with sepsis secondary to asplenia and the pneumococcus is responsible for over 50% of the cases. Normal spleen function and alteration in host defense occurring as a consequence of asplenia is discussed. Finally, alternatives to and indications for splenectomy as well as prophylactic measures are considered. It is concluded that, at the present time, antibiotic coverage for an indefinite period of time may be indicated for surgically or functionally asplenic patients. | [
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PMID:8651 | Some biological and physical properties of molluscum contagiosum virus propagated in cell culture. | Molluscum contagiosum virus propagated in FL cells of human amnion origin has a one-step growth cycle time of 12 to 14 h. The appearance and exponential increase of intracellular virus preceded the release of extracellular virus by approximately 2 h. Demonstration of comparable titers of extracellular and intracellular virus at the end of the replication cycle indicated that a substantial amount of virus remained associated with cells exhibiting cytopathogenic changes. Mean buoyant density values of virus in sucrose ranged from 1.275 to 1.278 g/cm3, but in CsCl the virus banded at densities at 1.325 to 1.340 and 1.261 to 1.281 g/cm3. Although virus infectivity was not affected by high concentrations of CsCl, it was found by polyacrylamide gel electrophoresis that the salt removed several nonglycosylated polypeptides with estimated molecular weights of 15,000 to 60,000. This suggested that the high-density band (1.325 to 1.340) may reflect the loss of these structural components. The half-life of virus infectivity was approximately 26.5 h at 26 degrees C and 11.2 h at 37 degrees C. Although the virus was rapidly inactivated at 50 degrees C, it could be stabilized at this temperature by the presence of 1.0 M MgCl2. Virus did not agglutinate newborn chick, adult chicken, or type "0" human erythrocytes. Virus infectivity was found to be sensitive to acid pH but resistant to treatment with diethyl ether or chloroform. The replication of molluscum virus in FL cells was not inhibited by 5-iodo-2'-deoxyuridine, 5-bromo-2'-deoxyuridine, or cytosine arabinonucleoside in noncytotoxic concentrations of 200 to 400 mug/ml, but greater than 99% reduction in the yield of herpes simplex virus or vaccinia virus in FL cells was obtained with 200 mug of these compounds per ml. Guanidinium chloride in concentrations of 100 to 200 mug/ml reduced molluscum virus yields by more than 99.9%. | Some biological and physical properties of molluscum contagiosum virus propagated in cell culture. Molluscum contagiosum virus propagated in FL cells of human amnion origin has a one-step growth cycle time of 12 to 14 h. The appearance and exponential increase of intracellular virus preceded the release of extracellular virus by approximately 2 h. Demonstration of comparable titers of extracellular and intracellular virus at the end of the replication cycle indicated that a substantial amount of virus remained associated with cells exhibiting cytopathogenic changes. Mean buoyant density values of virus in sucrose ranged from 1.275 to 1.278 g/cm3, but in CsCl the virus banded at densities at 1.325 to 1.340 and 1.261 to 1.281 g/cm3. Although virus infectivity was not affected by high concentrations of CsCl, it was found by polyacrylamide gel electrophoresis that the salt removed several nonglycosylated polypeptides with estimated molecular weights of 15,000 to 60,000. This suggested that the high-density band (1.325 to 1.340) may reflect the loss of these structural components. The half-life of virus infectivity was approximately 26.5 h at 26 degrees C and 11.2 h at 37 degrees C. Although the virus was rapidly inactivated at 50 degrees C, it could be stabilized at this temperature by the presence of 1.0 M MgCl2. Virus did not agglutinate newborn chick, adult chicken, or type "0" human erythrocytes. Virus infectivity was found to be sensitive to acid pH but resistant to treatment with diethyl ether or chloroform. The replication of molluscum virus in FL cells was not inhibited by 5-iodo-2'-deoxyuridine, 5-bromo-2'-deoxyuridine, or cytosine arabinonucleoside in noncytotoxic concentrations of 200 to 400 mug/ml, but greater than 99% reduction in the yield of herpes simplex virus or vaccinia virus in FL cells was obtained with 200 mug of these compounds per ml. Guanidinium chloride in concentrations of 100 to 200 mug/ml reduced molluscum virus yields by more than 99.9%. | [
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PMID:8652 | Characterization of some pneumococcal bacteriophages. | The growth of pneumococcal phages at high cell and phage densities is enhanced strongly by the substitution of potassium for sodium in the medium. Initial titers of 2 X 10(10) to 4 X 10(10) PFU/ml are readily obtained, and concentrated stocks are stable in a storage buffer described here. The mechanism of the cation effect is obscure. Phages omega3 and omega8 each have linear double-stranded DNA of 33 X 10(6) daltons per particle, with an apparent guanine plus cytosine content of 47 to 49 mol%, as determined by buoyancy and melting temperature, but with an unusual absorbance spectrum. Efficiency of plating is high if sufficient time is allowed for a relatively slow adsorption, which differs several-fold in rate between the two phages. Morphologically, these and other pneumococcal phages are similar to coliphage lambda but with a longer tail and tail fiber. Upon UV inactivation, omega3 and omega8 have D37 values of 33 and 55 J/m2, respectively, and each shows multiplicity reactivation. A total of 13 ts mutants have been isolated from the two phages, representing only two complementation groups; complementation and recombination occur between omega3 and omega8 mutants. Both phages provoke high-titer antisera with extensive cross-reactivity against a number of newly isolated pneumococcal phages. | Characterization of some pneumococcal bacteriophages. The growth of pneumococcal phages at high cell and phage densities is enhanced strongly by the substitution of potassium for sodium in the medium. Initial titers of 2 X 10(10) to 4 X 10(10) PFU/ml are readily obtained, and concentrated stocks are stable in a storage buffer described here. The mechanism of the cation effect is obscure. Phages omega3 and omega8 each have linear double-stranded DNA of 33 X 10(6) daltons per particle, with an apparent guanine plus cytosine content of 47 to 49 mol%, as determined by buoyancy and melting temperature, but with an unusual absorbance spectrum. Efficiency of plating is high if sufficient time is allowed for a relatively slow adsorption, which differs several-fold in rate between the two phages. Morphologically, these and other pneumococcal phages are similar to coliphage lambda but with a longer tail and tail fiber. Upon UV inactivation, omega3 and omega8 have D37 values of 33 and 55 J/m2, respectively, and each shows multiplicity reactivation. A total of 13 ts mutants have been isolated from the two phages, representing only two complementation groups; complementation and recombination occur between omega3 and omega8 mutants. Both phages provoke high-titer antisera with extensive cross-reactivity against a number of newly isolated pneumococcal phages. | [
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PMID:8659 | Mechanism of action of some bitter-tasting compounds on frog taste cells. | Effects of some bitter-tasting compounds on frog taste receptors were examined by recording glossopharyngeal nerve responses. The order of effectiveness of the compounds was quinine greater than brucine greater than formanilide greater than caffeine greater than urea. When the effects of quinine, brucine and caffeine on electrical responses in taste cells were examined, they all produced a depolarization associated with an increased input resistance. The action of the three compounds on taste receptors therefore, operates with a similar mechanism. The electrical responses in cells, produced by quinine, progressed slowly with time. Such effects with quinine are similar to those with procaine. After adaptation to quinine, the nerve responses to various chemical stimuli were gradually reduced in magnitude, while the electrical responses in taste cells during stimulation by chemicals became smaller. The mechanism of the effects of bitter stimuli are discussed in light of recent findings on the interaction of bitter stimuli with lipid monolayers and the extraction of lipid from bovine taste papillae by bitter stimuli. | Mechanism of action of some bitter-tasting compounds on frog taste cells. Effects of some bitter-tasting compounds on frog taste receptors were examined by recording glossopharyngeal nerve responses. The order of effectiveness of the compounds was quinine greater than brucine greater than formanilide greater than caffeine greater than urea. When the effects of quinine, brucine and caffeine on electrical responses in taste cells were examined, they all produced a depolarization associated with an increased input resistance. The action of the three compounds on taste receptors therefore, operates with a similar mechanism. The electrical responses in cells, produced by quinine, progressed slowly with time. Such effects with quinine are similar to those with procaine. After adaptation to quinine, the nerve responses to various chemical stimuli were gradually reduced in magnitude, while the electrical responses in taste cells during stimulation by chemicals became smaller. The mechanism of the effects of bitter stimuli are discussed in light of recent findings on the interaction of bitter stimuli with lipid monolayers and the extraction of lipid from bovine taste papillae by bitter stimuli. | [
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PMID:8660 | Evidences for alpha excitatory action of catecholamines on the electrical activity of the guinea-pig stomach. | Effects of catecholamines and their inhibitors on the electrical activity of the smooth muscle of the guinea-pig stomach were studied by using pressure electrodes. The spontaneous electrical activity of antrum and corpus preparations consisted of slow waves with or without superimposed spikes. In quiescent fundus preparations, the spike activity and slow waves were generated by TEA. Catecholamines (noradrenaline, isoprenaline and adrenaline) suppressed or blocked the spike discharges and the generation of slow waves. However, the spike activity was enhanced at a higher concentration of phenylephrine in the antrumand fundus preparations. Inhibitory responses of the smooth muscles from whole regions to adrenaline, noradrenaline or isoprenaline were antagonized by propranolol or DCI but not by phentolamine or phenoxybenzamine. Therefore, inhibitory actions of these amines appear to involve beta-adrenoceptors. After treatment with tetrodotoxin, noradrenaline and isoprenaline blocked the spike activity and the generation of slow waves. Phenylephrine or adrenaline potentiated the spike activity in the presence of tetrodotoxin. After treatment with DCI or propranolol, phenylephrine potentiated the spike activity of the antrum and fundus preparations. These excitatory effects were antagonized by phentolamine or phenoxybenzamine. It is concluded that excitatory actions of these amines are mediated by alpha-adrenoceptors rather than via a nervous pathway. | Evidences for alpha excitatory action of catecholamines on the electrical activity of the guinea-pig stomach. Effects of catecholamines and their inhibitors on the electrical activity of the smooth muscle of the guinea-pig stomach were studied by using pressure electrodes. The spontaneous electrical activity of antrum and corpus preparations consisted of slow waves with or without superimposed spikes. In quiescent fundus preparations, the spike activity and slow waves were generated by TEA. Catecholamines (noradrenaline, isoprenaline and adrenaline) suppressed or blocked the spike discharges and the generation of slow waves. However, the spike activity was enhanced at a higher concentration of phenylephrine in the antrumand fundus preparations. Inhibitory responses of the smooth muscles from whole regions to adrenaline, noradrenaline or isoprenaline were antagonized by propranolol or DCI but not by phentolamine or phenoxybenzamine. Therefore, inhibitory actions of these amines appear to involve beta-adrenoceptors. After treatment with tetrodotoxin, noradrenaline and isoprenaline blocked the spike activity and the generation of slow waves. Phenylephrine or adrenaline potentiated the spike activity in the presence of tetrodotoxin. After treatment with DCI or propranolol, phenylephrine potentiated the spike activity of the antrum and fundus preparations. These excitatory effects were antagonized by phentolamine or phenoxybenzamine. It is concluded that excitatory actions of these amines are mediated by alpha-adrenoceptors rather than via a nervous pathway. | [
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PMID:8661 | The electrogenesis of adrenaline-hyperpolarization of sympathetic ganglion cells in bullfrogs. | Bullfrog sympathetic ganglion cells produced hyperpolarizing (Ad-hyperpolarization) and depolarizing (Ad-depolarization) responses when adrenaline (Ad) was directly applied to ganglia. The nature of Ad-hyperpolarization recorded by the sucrose-gap method was analysed in the present experiment, in order to clarify its electrogenesis. The amplitude of Ad-hyperpolarization was increased or decreased while ganglion cell membranes were hyperpolarized or depolarized, respectively, by applying a moderate conditioning current to the ganglia. The Ad-hyperpolarization was depressed in K+-rich solutions as well as in K+-deficient solutions. It was not significantly altered by replacing the extracellular total Cl ions by equimolar glutamate or thiosulfate ions. Ad-hyperpolarization was depressed and finally abolished in the Na+-free Tris solution, and was reversibly eliminated in the solution where Na ions were totally replaced by equimolar Li ions. It was enhanced when a preparation was previously perfused in the K+-free, Na+-rich solution for certain periods, during which the intracellular Na+ concentration might be increased. Ad-hyperpolarization was depressed by lowering the temperature and by the action of ouabain, and the amplitude of Ad-hyperpolarization was markedly increased in the presence of TEA. The ionic mechanism underlying the generation of Ad-hyperpolarization was discussed on the basis of these present experimental results, and it was suggested that Ad-hyperpolarization might be generated by an electrogenic sodium pump. | The electrogenesis of adrenaline-hyperpolarization of sympathetic ganglion cells in bullfrogs. Bullfrog sympathetic ganglion cells produced hyperpolarizing (Ad-hyperpolarization) and depolarizing (Ad-depolarization) responses when adrenaline (Ad) was directly applied to ganglia. The nature of Ad-hyperpolarization recorded by the sucrose-gap method was analysed in the present experiment, in order to clarify its electrogenesis. The amplitude of Ad-hyperpolarization was increased or decreased while ganglion cell membranes were hyperpolarized or depolarized, respectively, by applying a moderate conditioning current to the ganglia. The Ad-hyperpolarization was depressed in K+-rich solutions as well as in K+-deficient solutions. It was not significantly altered by replacing the extracellular total Cl ions by equimolar glutamate or thiosulfate ions. Ad-hyperpolarization was depressed and finally abolished in the Na+-free Tris solution, and was reversibly eliminated in the solution where Na ions were totally replaced by equimolar Li ions. It was enhanced when a preparation was previously perfused in the K+-free, Na+-rich solution for certain periods, during which the intracellular Na+ concentration might be increased. Ad-hyperpolarization was depressed by lowering the temperature and by the action of ouabain, and the amplitude of Ad-hyperpolarization was markedly increased in the presence of TEA. The ionic mechanism underlying the generation of Ad-hyperpolarization was discussed on the basis of these present experimental results, and it was suggested that Ad-hyperpolarization might be generated by an electrogenic sodium pump. | [
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PMID:8662 | Simplified operative technique for the long-segment atypical coarctation of the aorta. | Simplified operative technique for the long-segment atypical coarctation of the aorta was described. The main objective of this technique is to gain quick access to both thoracic and abdominal aorta with minimal blood loss, and preservation of diaphragmatic function. This procedure consists of standard thoracotomy and pararectal incision with an entry into the retroperitoneal space. Long prosthetic graft was anastomosed in an end-to-side fashion to bypass the coarctated aorta. The graft is placed through peripheral circumference of the left hemidiaphragm, where phrenic nerve injury is not likely to occur. This technique was successfully applied to two cases of long-segment atypical coarctation of the aorta due to Takayasu's aortitis. Retroperitoneal placement of the graft prevents fatal hemorrhage due to direct contact with the graft. Contamination with transintestinal exudate can also be avoided. Results of the ten-year follow-up of the similar procedure in the literature is encouraging. | Simplified operative technique for the long-segment atypical coarctation of the aorta. Simplified operative technique for the long-segment atypical coarctation of the aorta was described. The main objective of this technique is to gain quick access to both thoracic and abdominal aorta with minimal blood loss, and preservation of diaphragmatic function. This procedure consists of standard thoracotomy and pararectal incision with an entry into the retroperitoneal space. Long prosthetic graft was anastomosed in an end-to-side fashion to bypass the coarctated aorta. The graft is placed through peripheral circumference of the left hemidiaphragm, where phrenic nerve injury is not likely to occur. This technique was successfully applied to two cases of long-segment atypical coarctation of the aorta due to Takayasu's aortitis. Retroperitoneal placement of the graft prevents fatal hemorrhage due to direct contact with the graft. Contamination with transintestinal exudate can also be avoided. Results of the ten-year follow-up of the similar procedure in the literature is encouraging. | [
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PMID:8663 | [Interrelations between blood pressure, blood volume, plasma renin and urinary catecholamines during beta-blockade in essential hypertension (author's transl)]. | Studies in 55 patients with benign essential hypertension showed that the beta-blockers bufuralol (22 patients) and propranolol (33 patients) at a dose ratio of 1:4, possess comparable antihypertensive efficacy despite different properties regarding intrinsic sympathomimetic activity. Beta-blocker-monotherapy normalized blood pressure ( less than 140/90 mm Hg) in one fourth of the patients. Body weight and plasma and blood volumes remained unchanged during beta-blockade of four to six weeks duration, the mean plasma potassium was slightly increased. The inhibition of plasma renin activity (PRA) was more pronounced with propranolol (-69%) than with bufuralol (-47%). Wirth both beta-blockers decreases in blood pressure correlated inversely with pre-treatment PRA (p less than 0.05). Propranolol-induced changes in blood pressure correlated also with associated changes in PRA (p less than 0.005); in contrast, no such relationship was observed with bufuralol. The blood pressure effects of bufuralol, however, correlated significantly with changes in urinary noradrenaline excretion (r=0.41; p less than 0.05). Patient sub-groups with low, normal or high pre-treatment PRA in the average showed a comparable pattern of pre-treatment noradrenaline excretion and patients with normal renin levels exreted more adrenaline than those with low renin levels (p less than 0.001). These data are consistent with the concept that in untreated essential hypertension PRA may be an index of adrenergic activiity, the latter representing an important determinant of blood pressure response to beta-blockade. The blood pressure lowering effects of bufuralol in benign essential hypertension seem to be independent of renin and may be related, at least partly, to diminished free peripheral noradrenaline levels. | [Interrelations between blood pressure, blood volume, plasma renin and urinary catecholamines during beta-blockade in essential hypertension (author's transl)]. Studies in 55 patients with benign essential hypertension showed that the beta-blockers bufuralol (22 patients) and propranolol (33 patients) at a dose ratio of 1:4, possess comparable antihypertensive efficacy despite different properties regarding intrinsic sympathomimetic activity. Beta-blocker-monotherapy normalized blood pressure ( less than 140/90 mm Hg) in one fourth of the patients. Body weight and plasma and blood volumes remained unchanged during beta-blockade of four to six weeks duration, the mean plasma potassium was slightly increased. The inhibition of plasma renin activity (PRA) was more pronounced with propranolol (-69%) than with bufuralol (-47%). Wirth both beta-blockers decreases in blood pressure correlated inversely with pre-treatment PRA (p less than 0.05). Propranolol-induced changes in blood pressure correlated also with associated changes in PRA (p less than 0.005); in contrast, no such relationship was observed with bufuralol. The blood pressure effects of bufuralol, however, correlated significantly with changes in urinary noradrenaline excretion (r=0.41; p less than 0.05). Patient sub-groups with low, normal or high pre-treatment PRA in the average showed a comparable pattern of pre-treatment noradrenaline excretion and patients with normal renin levels exreted more adrenaline than those with low renin levels (p less than 0.001). These data are consistent with the concept that in untreated essential hypertension PRA may be an index of adrenergic activiity, the latter representing an important determinant of blood pressure response to beta-blockade. The blood pressure lowering effects of bufuralol in benign essential hypertension seem to be independent of renin and may be related, at least partly, to diminished free peripheral noradrenaline levels. | [
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PMID:8664 | [Specific and non-specific effects of beta-adreno-receptor blocking drugs in man (author's transl)]. | The effect of tyramine infusion or exercise on catecholamine concentration and dopamine-beta-hydroxylase activity in plasma of normal volunteers has been studied. Whereas the increase in plasma catecholamine concentrations by tyramine infusion was not changed 90 min after oral application of a single dose of beta-adrenoceptor blocking drugs (penbutolol, practolol, I.C.I. 66082), the increase in blood pressure was diminished. However, the increase in plasma catecholamine, concentration, i.e. the adrenergic response to exercise was significantly enhanced during beta-adrenoceptor blockade. On the other hand, dopamine-beta-hydroxylase activity was not further increased during beta-adrenoceptor blockade. - The non-specific membrane activity of the beta-adrenoceptor blocking drugs wass assessed by the degree of inhibition of serotonin uptake by human platelets in vitro. Their order of potency, according to IC 50 values estimated from the dose response curves was: propranolol less than penbutolol less than practolol less than I.C.I. 66082. The inhibitory activity of these drugs in vivo was also studied by measuring serotonin uptake by platelets isolated 90 min after oral administration. Due to the high dose only propranolol showed a marked membrane activity. | [Specific and non-specific effects of beta-adreno-receptor blocking drugs in man (author's transl)]. The effect of tyramine infusion or exercise on catecholamine concentration and dopamine-beta-hydroxylase activity in plasma of normal volunteers has been studied. Whereas the increase in plasma catecholamine concentrations by tyramine infusion was not changed 90 min after oral application of a single dose of beta-adrenoceptor blocking drugs (penbutolol, practolol, I.C.I. 66082), the increase in blood pressure was diminished. However, the increase in plasma catecholamine, concentration, i.e. the adrenergic response to exercise was significantly enhanced during beta-adrenoceptor blockade. On the other hand, dopamine-beta-hydroxylase activity was not further increased during beta-adrenoceptor blockade. - The non-specific membrane activity of the beta-adrenoceptor blocking drugs wass assessed by the degree of inhibition of serotonin uptake by human platelets in vitro. Their order of potency, according to IC 50 values estimated from the dose response curves was: propranolol less than penbutolol less than practolol less than I.C.I. 66082. The inhibitory activity of these drugs in vivo was also studied by measuring serotonin uptake by platelets isolated 90 min after oral administration. Due to the high dose only propranolol showed a marked membrane activity. | [
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PMID:8669 | The absorption of warfarin from the rat stomach in situ. | The absorption of warfarin from rat stomach was studied in situ by measuring the warfarin concentration in the gastric fluid, plasma, and the gastric wall concurrently. The warfarin concentrations in gastric fluid with initially acidic pH (pH 3 and pH 5) declined more rapidly than in initially neutral (pH 7) or basic (pH 8) fluid. However, the concurrent measurement of warfarin concentrations in plasma revealed that the absorption from initially neutral or basic fluids was faster in comparison with that measured from initially acidic milieu. This discrepancy resulted from a substantial accumulation of warfarin in the gastric wall mainly on mucosa due to the precipitation of the drug in acidic environment. | The absorption of warfarin from the rat stomach in situ. The absorption of warfarin from rat stomach was studied in situ by measuring the warfarin concentration in the gastric fluid, plasma, and the gastric wall concurrently. The warfarin concentrations in gastric fluid with initially acidic pH (pH 3 and pH 5) declined more rapidly than in initially neutral (pH 7) or basic (pH 8) fluid. However, the concurrent measurement of warfarin concentrations in plasma revealed that the absorption from initially neutral or basic fluids was faster in comparison with that measured from initially acidic milieu. This discrepancy resulted from a substantial accumulation of warfarin in the gastric wall mainly on mucosa due to the precipitation of the drug in acidic environment. | [
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PMID:8670 | Regional changes in [3H]-noradrenaline uptake, catecholamines and catecholamine synthetic and catabolic enzymes in rat brain following neonatal 6-hydroxydopamine treatment. | 6-Hydroxydopamine (6-OH-DA) treatment of rats at birth (with the analyses conducted in the adult stage) produced marked regional variations in changes in endogenous noradrenaline (NA) and [3H]NA uptake in the CNS. The most pronounced reductions were seen in the cerebral cortex, hippocampus and the spinal cord. Moderate changes or none at all were seen in the hypothalamus, septum and thalamus. Marked increases in endogenous NA and [3H]NA uptake were seen in the mesencephalon and the pons-medulla oblongata. There was in general a close correlation between the changes in endogenous NA and [3H]NA uptake. The results from the cerebellum varied, depending on the developmental stage at which the 6-OH-DA treatment was performed. 6-OH-DA treatment up to three days after birth generally led to a marked increase in both endogenous NA and [3H]NA uptake, while continuing the treatment caused a marked reduction of both parameters. The 6-OH-DA treatment caused no changes in endogenous dopamine (DA) in all regions analysed. Enzyme activity assays showed that DA-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) were greatly reduced in the cerebral cortex, while the activity of both enzymes was almost double in the pons-medulla. No changes in the activity of phenylethanol-amine N-methyltransferase (PNMT), DOPA decarboxylase, COMT and MAO were seen after 6-OH-DA at birth. Measurements of choline acetyltransferase activity displayed only minute changes. The present results strongly support the view that 6-OH-DA treatment in the neonate stage produces a very selective action on NA neurones belonging to the locus coeruleus system from a structural standpoint, leaving DA- and PNMT-containing neurones unaffected. [3H]NA uptake in whole CNS was almost unchanged, despite the marked regional variations. The results have been interpreted as being due to a 'pruning effect', where the permanent NA denervation in distant nerve terminal projections (e.g. cerebral cortex) leads to a compensatory sprouting and increased outgrowth of NA terminal projections in areas close to the perikarya (e.g. pons-medulla). Furthermore, the results support the view that the growing locus coeruleus neurones are strictly programmed to produce a certain quantity of nerve terminal volume and arborization during the postnatal development. | Regional changes in [3H]-noradrenaline uptake, catecholamines and catecholamine synthetic and catabolic enzymes in rat brain following neonatal 6-hydroxydopamine treatment. 6-Hydroxydopamine (6-OH-DA) treatment of rats at birth (with the analyses conducted in the adult stage) produced marked regional variations in changes in endogenous noradrenaline (NA) and [3H]NA uptake in the CNS. The most pronounced reductions were seen in the cerebral cortex, hippocampus and the spinal cord. Moderate changes or none at all were seen in the hypothalamus, septum and thalamus. Marked increases in endogenous NA and [3H]NA uptake were seen in the mesencephalon and the pons-medulla oblongata. There was in general a close correlation between the changes in endogenous NA and [3H]NA uptake. The results from the cerebellum varied, depending on the developmental stage at which the 6-OH-DA treatment was performed. 6-OH-DA treatment up to three days after birth generally led to a marked increase in both endogenous NA and [3H]NA uptake, while continuing the treatment caused a marked reduction of both parameters. The 6-OH-DA treatment caused no changes in endogenous dopamine (DA) in all regions analysed. Enzyme activity assays showed that DA-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) were greatly reduced in the cerebral cortex, while the activity of both enzymes was almost double in the pons-medulla. No changes in the activity of phenylethanol-amine N-methyltransferase (PNMT), DOPA decarboxylase, COMT and MAO were seen after 6-OH-DA at birth. Measurements of choline acetyltransferase activity displayed only minute changes. The present results strongly support the view that 6-OH-DA treatment in the neonate stage produces a very selective action on NA neurones belonging to the locus coeruleus system from a structural standpoint, leaving DA- and PNMT-containing neurones unaffected. [3H]NA uptake in whole CNS was almost unchanged, despite the marked regional variations. The results have been interpreted as being due to a 'pruning effect', where the permanent NA denervation in distant nerve terminal projections (e.g. cerebral cortex) leads to a compensatory sprouting and increased outgrowth of NA terminal projections in areas close to the perikarya (e.g. pons-medulla). Furthermore, the results support the view that the growing locus coeruleus neurones are strictly programmed to produce a certain quantity of nerve terminal volume and arborization during the postnatal development. | [
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PMID:8671 | [Stellate ganglion blocks and vasodilator drugs in the treatment of perceptive deafness (author's transl)]. | The results in the treatment of the idiopathetic perceptive deafness by means of stellate ganglion blocks and vasodilator drugs have been recorded. From 89 treated ears, 54% showed an improvement (some of them to a considerable degree). However, in 46% of the cases no significant improvement was effected. | [Stellate ganglion blocks and vasodilator drugs in the treatment of perceptive deafness (author's transl)]. The results in the treatment of the idiopathetic perceptive deafness by means of stellate ganglion blocks and vasodilator drugs have been recorded. From 89 treated ears, 54% showed an improvement (some of them to a considerable degree). However, in 46% of the cases no significant improvement was effected. | [
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PMID:8697 | Chlorate toxicity in Aspergillus nidulans. Studies of mutants altered in nitrate assimilation. | It had previously been held that chlorate is not itself toxic, but is rendered toxic as a result of nitrate reductase-catalysed conversion to chlorite. This however cannot be the explanation of chlorate toxicity in Aspergillus nidulans, even though nitrate reductase is known to have chlorate reductase activity. Among other evidence against the classical theory for the mechanism of chlorate toxicity, is the finding that not all mutants lacking nitrate reductase are clorate resistant. Both chlorate-sensitive and resistant mutants lacking nitrate reductase, also lack chlorate reductase. Data is presented which implicates not only nitrate reductase but also the product of the nirA gene, a positive regulator gene for nitrate assimilation, in the mediation of chlorate toxicity. Alternative mechanisms for chlorate toxicity are considered. It is unlikely that chlorate toxicity results from the involvement of nitrate reductase and the nirA gene product in the regulation either of nitrite reductase, or of the pentose phosphate pathway. Although low pH has an effect similar to chlorate, chorate is not likely to be toxic because it lowers the pH; low pH and chlorate may instead have similar effects. A possible explanation for chlorate toxicity is that it mimics nitrate in mediating, via nitrate reductase and the nirA gene product, a shut-down of nitrogen catabolism. As chlorate cannot act as a nitrogen source, nitrogen starvation ensues. | Chlorate toxicity in Aspergillus nidulans. Studies of mutants altered in nitrate assimilation. It had previously been held that chlorate is not itself toxic, but is rendered toxic as a result of nitrate reductase-catalysed conversion to chlorite. This however cannot be the explanation of chlorate toxicity in Aspergillus nidulans, even though nitrate reductase is known to have chlorate reductase activity. Among other evidence against the classical theory for the mechanism of chlorate toxicity, is the finding that not all mutants lacking nitrate reductase are clorate resistant. Both chlorate-sensitive and resistant mutants lacking nitrate reductase, also lack chlorate reductase. Data is presented which implicates not only nitrate reductase but also the product of the nirA gene, a positive regulator gene for nitrate assimilation, in the mediation of chlorate toxicity. Alternative mechanisms for chlorate toxicity are considered. It is unlikely that chlorate toxicity results from the involvement of nitrate reductase and the nirA gene product in the regulation either of nitrite reductase, or of the pentose phosphate pathway. Although low pH has an effect similar to chlorate, chorate is not likely to be toxic because it lowers the pH; low pH and chlorate may instead have similar effects. A possible explanation for chlorate toxicity is that it mimics nitrate in mediating, via nitrate reductase and the nirA gene product, a shut-down of nitrogen catabolism. As chlorate cannot act as a nitrogen source, nitrogen starvation ensues. | [
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PMID:8702 | Some properties of the adenosine triphosphatase systems of two yeast species, Saccharomyces cerevisiae and Rhodotorula glutinis. | 1. Total ATPase levels were determined in homogenate fractions of baker's yeast, Saccharomyces cerevisiae K and Rhodotorula glutinis. The maximum ATPase activities in 8000 X g supernatant of the three yeast strains were 6.0, 1.9, and 2.2 mmol Pih-1 (gDS)-1, respectively; the activities in the sediment were somewhat higher. Exponential cells of S. cerevisiae K and R. glutinis exhibited higher ATPase levels than did the stationary cells. 2. The total ATPase activity in both yeast species showed a maximum at ph 6.8 a minimum at pH 7.2, and another broader masimum around pH 8.0. 3. No significant NaK-ATPase activity was detected in baker's yeast, in either the exponential or the stationary cells of R. glutinis, and in exponential S. cerevisiae K cells in the pH range of 6.0-9.3. 4. Stationary cells of S. cerevisiae K exhibited, at pH 7.0-8.5, A Na,K-ATPase activity attaining 9% of total ATPase level. 5.3 X 10(-3) M phenylmethyl sulphonyl fluoride had no effect on the total ATPase level in S. cerevisiae and inhibited the activity in R. glutinis by 25%; it did not bring forth any Na,K-ATPase activity apart from that found in its absence. 6. 1.5 M urea lowered the ATPase activity in R. glutinis by 68% but had no effect on S. cerevisiae cells. 10(-5) M dicyclohexylcarbodiimide suppressed the ATPase activity in S. cerevisiae and R. glutinis by 74 and 79%, respectively. Neither agent revealed and additional Na,K-ATPase activity. 7. The comparison of Na,K-ATPase activities with data on K+ fluxes across the yeast plasma membrane suggested that even with the lower flux values the Na,K-ATPase, even if present, would account for a mere 40% of transported ions. The results imply that the active ion transport in yeasts is energized by mechanisms other than the Na,K-ATPase. | Some properties of the adenosine triphosphatase systems of two yeast species, Saccharomyces cerevisiae and Rhodotorula glutinis. 1. Total ATPase levels were determined in homogenate fractions of baker's yeast, Saccharomyces cerevisiae K and Rhodotorula glutinis. The maximum ATPase activities in 8000 X g supernatant of the three yeast strains were 6.0, 1.9, and 2.2 mmol Pih-1 (gDS)-1, respectively; the activities in the sediment were somewhat higher. Exponential cells of S. cerevisiae K and R. glutinis exhibited higher ATPase levels than did the stationary cells. 2. The total ATPase activity in both yeast species showed a maximum at ph 6.8 a minimum at pH 7.2, and another broader masimum around pH 8.0. 3. No significant NaK-ATPase activity was detected in baker's yeast, in either the exponential or the stationary cells of R. glutinis, and in exponential S. cerevisiae K cells in the pH range of 6.0-9.3. 4. Stationary cells of S. cerevisiae K exhibited, at pH 7.0-8.5, A Na,K-ATPase activity attaining 9% of total ATPase level. 5.3 X 10(-3) M phenylmethyl sulphonyl fluoride had no effect on the total ATPase level in S. cerevisiae and inhibited the activity in R. glutinis by 25%; it did not bring forth any Na,K-ATPase activity apart from that found in its absence. 6. 1.5 M urea lowered the ATPase activity in R. glutinis by 68% but had no effect on S. cerevisiae cells. 10(-5) M dicyclohexylcarbodiimide suppressed the ATPase activity in S. cerevisiae and R. glutinis by 74 and 79%, respectively. Neither agent revealed and additional Na,K-ATPase activity. 7. The comparison of Na,K-ATPase activities with data on K+ fluxes across the yeast plasma membrane suggested that even with the lower flux values the Na,K-ATPase, even if present, would account for a mere 40% of transported ions. The results imply that the active ion transport in yeasts is energized by mechanisms other than the Na,K-ATPase. | [
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PMID:8703 | Oxidation of S-e-carboxymethyl-selenocysteine by L-aminoacid oxidase and by D-aspartate oxidase. | Se-Carboxymethyl-DL-selnocysteine (CMSeC) has been prepared in a pure crystalline form from selenocysteine and monochloracetic acid. It has been shown that CMSeC is a substrate for the L-aminoacid oxidase form snake venom and for the D-aspartate oxidase from beef kidney. Oxygen consumption and ammonia production indicate that only the L or the D form of CMSeC ar acted upon respectively by one or the other of the above enzymes. No noticeable differences were shown in the oxidation rate of CMSeC and S-carboxymethylcysteine, an indication that the substitution of a selenium for a sulfur atom in the molecule does not greatly affect the substrate specificity of the two enzymes. Data have been obtained suggesting that the product of the oxidative deamination of CMSeC Is Se-carboxymethyl-selenopyruvic acid. | Oxidation of S-e-carboxymethyl-selenocysteine by L-aminoacid oxidase and by D-aspartate oxidase. Se-Carboxymethyl-DL-selnocysteine (CMSeC) has been prepared in a pure crystalline form from selenocysteine and monochloracetic acid. It has been shown that CMSeC is a substrate for the L-aminoacid oxidase form snake venom and for the D-aspartate oxidase from beef kidney. Oxygen consumption and ammonia production indicate that only the L or the D form of CMSeC ar acted upon respectively by one or the other of the above enzymes. No noticeable differences were shown in the oxidation rate of CMSeC and S-carboxymethylcysteine, an indication that the substitution of a selenium for a sulfur atom in the molecule does not greatly affect the substrate specificity of the two enzymes. Data have been obtained suggesting that the product of the oxidative deamination of CMSeC Is Se-carboxymethyl-selenopyruvic acid. | [
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PMID:8704 | Studies on selenium-related compounds. V. Cytogenetic effect and reactivity with DNA. | Five selenium compounds, Na2Se04, H2Se04, Na2Se03, H2Se03 and Se02, were tested for their capacity to induce chromosome aberrations in cultured human leukocytes and for their reactivity with DNA by a rec-assay system and inactivation of transforming activity in Bacillus subtilis. Chromosome-breaking activity was significantly higher for the compounds with four-valent than with six-valent selenium, the efficiency being in the decreasing order H2S03 greater than Na2Se03 greater than Se02 greater than H2Se04 greater than Na2Se04. Rec assay using B. subtilis with different recombination capacities suggested that damage to DNA was produced by selenites but not by selenates. The reactivity of selenites with DNA was also indicated by a significant loss of transformation of the tryptophan marker of B. subtilis DNA treated with H2Se03 and Se02. | Studies on selenium-related compounds. V. Cytogenetic effect and reactivity with DNA. Five selenium compounds, Na2Se04, H2Se04, Na2Se03, H2Se03 and Se02, were tested for their capacity to induce chromosome aberrations in cultured human leukocytes and for their reactivity with DNA by a rec-assay system and inactivation of transforming activity in Bacillus subtilis. Chromosome-breaking activity was significantly higher for the compounds with four-valent than with six-valent selenium, the efficiency being in the decreasing order H2S03 greater than Na2Se03 greater than Se02 greater than H2Se04 greater than Na2Se04. Rec assay using B. subtilis with different recombination capacities suggested that damage to DNA was produced by selenites but not by selenates. The reactivity of selenites with DNA was also indicated by a significant loss of transformation of the tryptophan marker of B. subtilis DNA treated with H2Se03 and Se02. | [
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PMID:8706 | New method for evaluation of freshness degree in fish and its products. | The method is based on the determination of the content of fish meat of soluble, non-heat-precipitable protein which is brought in relation to the total amount of sarcoplasmic protein. The method is also suited to evaluate the freshness of iced fish where other procedures sometimes fail, which is due to the interference of the melted ice. | New method for evaluation of freshness degree in fish and its products. The method is based on the determination of the content of fish meat of soluble, non-heat-precipitable protein which is brought in relation to the total amount of sarcoplasmic protein. The method is also suited to evaluate the freshness of iced fish where other procedures sometimes fail, which is due to the interference of the melted ice. | [
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PMID:8714 | [Dry matter losses in mushroom (Lactarius rufus) by blanching]. | According to recommended international standards edible fungi are blanched before salting and freezing. A study was conducted on the solution losses of Lactarius rufus due to blanching. Weight losses, changes of dry matter, raw fat, total nitrogen, amino nitrogen and ash contents as well as the pH value were determined when various methods of blanching were used. 3 min blanching at 95-100 degrees C was able to inactivate catalase and peroxydase while 6 min blanching was needed for inactivating polyphenoloxydase totally. After blanching there were 1/10 - 1/100 of spores left. During the 3 min blanching in water five times the quantity of mushrooms the losses of dry matter were about 10%; when doubling the quantity of blanching water the losses increased to 2-3 fold. The doubling of blanching time had no significant influence on the losses. The soluble dry matter content of blanched mushrooms was less than 50% of that of the fresh. Total nitrogen of fresh mushrooms was equal to that of the blanched but the amino nitrogen decreased to one tenth by blanching. The mineral element content of blanched mushrooms was about the half of that of the fresh. Blanching caused a slight decrease in the pH value. The necessity of the blanching of all edible fungi before freezing was discussed. | [Dry matter losses in mushroom (Lactarius rufus) by blanching]. According to recommended international standards edible fungi are blanched before salting and freezing. A study was conducted on the solution losses of Lactarius rufus due to blanching. Weight losses, changes of dry matter, raw fat, total nitrogen, amino nitrogen and ash contents as well as the pH value were determined when various methods of blanching were used. 3 min blanching at 95-100 degrees C was able to inactivate catalase and peroxydase while 6 min blanching was needed for inactivating polyphenoloxydase totally. After blanching there were 1/10 - 1/100 of spores left. During the 3 min blanching in water five times the quantity of mushrooms the losses of dry matter were about 10%; when doubling the quantity of blanching water the losses increased to 2-3 fold. The doubling of blanching time had no significant influence on the losses. The soluble dry matter content of blanched mushrooms was less than 50% of that of the fresh. Total nitrogen of fresh mushrooms was equal to that of the blanched but the amino nitrogen decreased to one tenth by blanching. The mineral element content of blanched mushrooms was about the half of that of the fresh. Blanching caused a slight decrease in the pH value. The necessity of the blanching of all edible fungi before freezing was discussed. | [
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PMID:8716 | [Complex gels of proteins and acid polysaccharides]. | The authors studied the thermomechanical properties of complex gels of gelatin and sodium alginate which had been produced on the basis of their insoluble (type I) and soluble (type II) complexes. Compared to gelatin gels of the same concentration, the complex gels I have higher melting points. The latter depend on the pH value at which the insoluble complexes of gelatin and sodium alginate were separated. Up to temperatures from 70 degrees--80 degrees C., no melting of the complex gels II was observed. The aging time and the composition of the soluble complexes of gelatin and sodium alginate exert no marked effects on the properties of the complex gels II. The soluble complexes of gelatin and sodium alginate can form gels in 7 M urea solutions. | [Complex gels of proteins and acid polysaccharides]. The authors studied the thermomechanical properties of complex gels of gelatin and sodium alginate which had been produced on the basis of their insoluble (type I) and soluble (type II) complexes. Compared to gelatin gels of the same concentration, the complex gels I have higher melting points. The latter depend on the pH value at which the insoluble complexes of gelatin and sodium alginate were separated. Up to temperatures from 70 degrees--80 degrees C., no melting of the complex gels II was observed. The aging time and the composition of the soluble complexes of gelatin and sodium alginate exert no marked effects on the properties of the complex gels II. The soluble complexes of gelatin and sodium alginate can form gels in 7 M urea solutions. | [
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PMID:8717 | [Structure and properties of complex gels of gelatin and pectin]. | The authors studied the effects of aging time and composition on the thermomechanical properties of complex gels of gelatin and pectin which had been produced on the basis of complexes obtained at pH values below the isoelectric point of gelatin. With aging for up to 7 days, the elasticity of the gels decreases and the melting points are raised by 2--4degreesC. An increase in the relative content of pectin in the complex leads to a considerable rise of the melting point of the complex gel. The increase in heat stability of these gels is explained by the development of an ion lattice, which is due to the interaction of the oppositely charged groups of the pectin and the gelatin. Furthermore, hydrophobic interactions between the non-polar groups of the components might be involved. | [Structure and properties of complex gels of gelatin and pectin]. The authors studied the effects of aging time and composition on the thermomechanical properties of complex gels of gelatin and pectin which had been produced on the basis of complexes obtained at pH values below the isoelectric point of gelatin. With aging for up to 7 days, the elasticity of the gels decreases and the melting points are raised by 2--4degreesC. An increase in the relative content of pectin in the complex leads to a considerable rise of the melting point of the complex gel. The increase in heat stability of these gels is explained by the development of an ion lattice, which is due to the interaction of the oppositely charged groups of the pectin and the gelatin. Furthermore, hydrophobic interactions between the non-polar groups of the components might be involved. | [
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PMID:8718 | [Significance of starter cultures for raw sausage aging in view of food and nutrition hygiene]. | The authors studied the effects of liquid starter cultures on the survival of pathogenic germs. It was found that the foreign bacteria tested differed in growth limitation which is obviously dependent on acidity and the amount of lactic acid produced by fermentation. Since the pathogenic bacteria differ in the ability to survive, it is imperative to observe strict hygienic measures in preparing starter cultures and to use absolutely sterile monocultures for raw sausage ageing. | [Significance of starter cultures for raw sausage aging in view of food and nutrition hygiene]. The authors studied the effects of liquid starter cultures on the survival of pathogenic germs. It was found that the foreign bacteria tested differed in growth limitation which is obviously dependent on acidity and the amount of lactic acid produced by fermentation. Since the pathogenic bacteria differ in the ability to survive, it is imperative to observe strict hygienic measures in preparing starter cultures and to use absolutely sterile monocultures for raw sausage ageing. | [
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PMID:8719 | [Rheology and spinning of alkaline solution of field bean protein and casein]. | From field bean protein and a mixture of field bean protein with casein to equal parts are prepared with sodium hydroxide high protein-containing alkaline solutions, which show pseudoplastic flow. The flow curves of the pseudoplastic field bean protein-casein (I:I)-solutions are described mathematically with the Ostwaldian power statement. In a suitable scope of spinning of this solutions are carried out complete factorial experiments, which guide to regression equations of lg k and n. g k depends on the concentration of protein; an effect of the sodium hydroxide concentration exists lonly about interactions. On the other hand the flow exponent n depends on the hydroxide concentration. The properties of the spun field bean protein/casein (I:I) fibres are described. | [Rheology and spinning of alkaline solution of field bean protein and casein]. From field bean protein and a mixture of field bean protein with casein to equal parts are prepared with sodium hydroxide high protein-containing alkaline solutions, which show pseudoplastic flow. The flow curves of the pseudoplastic field bean protein-casein (I:I)-solutions are described mathematically with the Ostwaldian power statement. In a suitable scope of spinning of this solutions are carried out complete factorial experiments, which guide to regression equations of lg k and n. g k depends on the concentration of protein; an effect of the sodium hydroxide concentration exists lonly about interactions. On the other hand the flow exponent n depends on the hydroxide concentration. The properties of the spun field bean protein/casein (I:I) fibres are described. | [
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PMID:8722 | [Effects of technological additives and heating range on some chemical and physical changes in canned meat. 2. Changes in redox potentials and selected quality characteristics]. | The influence of technological additives and the range of heating on the redox potential, as well as on some quality features of canned meat was examined. The experiments showed, that the time of storage and the degree of heating of model preserves of meat influence on the redox potential. The technological additions as polyphosphates, ascorbic acid, gelatine and mixtures of these substances influence less on the redox potential. The analysis of each experimental factor showed, that on the secretion of meat juice occurring during can pasteurization or sterilization influence all experimental factors, as the kind of heating, the time of storage as well as the kind and the quantity of technological additives. The highest secretion of meat juice was found in cans with addition of ascorbic acid. Cans with addition of gelatine had the smallest content of jelly and consequently the lowest secretion of meat juice. It was also found a certain relation between the level of redox potential and the tested quality features of the model meat preserves. | [Effects of technological additives and heating range on some chemical and physical changes in canned meat. 2. Changes in redox potentials and selected quality characteristics]. The influence of technological additives and the range of heating on the redox potential, as well as on some quality features of canned meat was examined. The experiments showed, that the time of storage and the degree of heating of model preserves of meat influence on the redox potential. The technological additions as polyphosphates, ascorbic acid, gelatine and mixtures of these substances influence less on the redox potential. The analysis of each experimental factor showed, that on the secretion of meat juice occurring during can pasteurization or sterilization influence all experimental factors, as the kind of heating, the time of storage as well as the kind and the quantity of technological additives. The highest secretion of meat juice was found in cans with addition of ascorbic acid. Cans with addition of gelatine had the smallest content of jelly and consequently the lowest secretion of meat juice. It was also found a certain relation between the level of redox potential and the tested quality features of the model meat preserves. | [
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PMID:8723 | [Characterization and spinning of alkaline solutions of wheat protein and casein]. | The viscosity behaviour of alkaline solutions of mixtures from different wheat glutens with casein in dependence on the concentration of the whole protein, wheat protein, sodium hydroxide, sodium chloride and on the temperature, time and the effect of treatment of wet wheat gluten with sodium chloride or sodium hydroxide on the properties of the spun wheat protein/casein fibers are described. Based on this model experiments the rheological behaviour of alkaline solutions of wheat protein/casein (I:2) and proceed from the parameters of the spinning process the properties of the corresponding spun fibers are represented. | [Characterization and spinning of alkaline solutions of wheat protein and casein]. The viscosity behaviour of alkaline solutions of mixtures from different wheat glutens with casein in dependence on the concentration of the whole protein, wheat protein, sodium hydroxide, sodium chloride and on the temperature, time and the effect of treatment of wet wheat gluten with sodium chloride or sodium hydroxide on the properties of the spun wheat protein/casein fibers are described. Based on this model experiments the rheological behaviour of alkaline solutions of wheat protein/casein (I:2) and proceed from the parameters of the spinning process the properties of the corresponding spun fibers are represented. | [
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PMID:8729 | Intracellular pH and activation of sea urchin eggs after fertilisation. | The intracellular pH of the sea urchin embryo increases 0.3 pH units between 1 and 4 min after fertilisation. The increase in pH is required for initiating development. The increase results from an exchange of extracellular Na+ for intracellular H+. | Intracellular pH and activation of sea urchin eggs after fertilisation. The intracellular pH of the sea urchin embryo increases 0.3 pH units between 1 and 4 min after fertilisation. The increase in pH is required for initiating development. The increase results from an exchange of extracellular Na+ for intracellular H+. | [
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PMID:8732 | Formation of stable crystalline enzyme-substrate intermediates at sub-zero temperatures. | Sub-zero temperatures can be used to trap intermediates in enzyme-catalysed reactions using suitable cryosolvents. The feasibility of obtaining such intermediates in the crystalline state for X-ray diffraction studies has been demonstrated with several proteases, using specific substrates and optimal pH. | Formation of stable crystalline enzyme-substrate intermediates at sub-zero temperatures. Sub-zero temperatures can be used to trap intermediates in enzyme-catalysed reactions using suitable cryosolvents. The feasibility of obtaining such intermediates in the crystalline state for X-ray diffraction studies has been demonstrated with several proteases, using specific substrates and optimal pH. | [
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PMID:8734 | Central action of a catechol-amide seizure-inducing agent: opposing effect on tyrosine and tryptophan hydroxylase activity in vivo. | The audiogenic seizure-inducing drug H13/04 was found to elicit opposing effects on the in vivo accumulation of 5-HTP (5-hydroxytryptophan) and DOPA (3,4-dihydroxyphenylalanine) in the brain following inhibition of L-amino acid decarboxylase. In strains of mice that normally do not exhibit audiogenic seizures, H13/04 retarded the accumulation of 5-HTP in the telencephalon, diencephalon and brainstem and enhanced the accumulation DOPA in the diencephalon and brainstem. The duration of the biochemical action of H13/04-correlated with the duration of the behavioral effect. When H13/04 is administered to strains of mice with a genetically-determined susceptibility to audiogenic seizures, but at an age when they are developing resistance to seizures, H13/04 does not alter the incidence of sound-induced seizures. The effect on the accumulation of 5-HTP and DOPA was similar to that noted in the genetically-resistant strain; a retardation of the accumulation of 5-HTP in the telencephalon and brainstem and an enhancement of DOPA accumulation in the brainstem. Since the rate of accumulation of 5-HTP and DOPA is a measure of the in vivo rates of tryptophan and tyrosine hydroxylase, respectively, the results may reflect changes in neural activity with consequent effects on the synthesizing enzymes. These results emphasize the usefulness of the drug in analyzing central mechanisms underlying audiogenic seizure activity and in studying functional properties and interactions of the central catechol-and indoleamine systems. | Central action of a catechol-amide seizure-inducing agent: opposing effect on tyrosine and tryptophan hydroxylase activity in vivo. The audiogenic seizure-inducing drug H13/04 was found to elicit opposing effects on the in vivo accumulation of 5-HTP (5-hydroxytryptophan) and DOPA (3,4-dihydroxyphenylalanine) in the brain following inhibition of L-amino acid decarboxylase. In strains of mice that normally do not exhibit audiogenic seizures, H13/04 retarded the accumulation of 5-HTP in the telencephalon, diencephalon and brainstem and enhanced the accumulation DOPA in the diencephalon and brainstem. The duration of the biochemical action of H13/04-correlated with the duration of the behavioral effect. When H13/04 is administered to strains of mice with a genetically-determined susceptibility to audiogenic seizures, but at an age when they are developing resistance to seizures, H13/04 does not alter the incidence of sound-induced seizures. The effect on the accumulation of 5-HTP and DOPA was similar to that noted in the genetically-resistant strain; a retardation of the accumulation of 5-HTP in the telencephalon and brainstem and an enhancement of DOPA accumulation in the brainstem. Since the rate of accumulation of 5-HTP and DOPA is a measure of the in vivo rates of tryptophan and tyrosine hydroxylase, respectively, the results may reflect changes in neural activity with consequent effects on the synthesizing enzymes. These results emphasize the usefulness of the drug in analyzing central mechanisms underlying audiogenic seizure activity and in studying functional properties and interactions of the central catechol-and indoleamine systems. | [
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PMID:8735 | The cardiovascular effects of intraventricularly administered histamine in the anaesthetised rat. | In urethane-anaestetised rats intraventricular (i.c.v.) injections of histamine (0.1-10.0mug) elicited dose-related rises in both the resting blood pressure and heart rate. These cardiovascular effects of histamine were antagonised in a dose-dependent manner by i.c.v. pretreatments with the histamine H1-receptor antagonists mepyramine (10, 50 and 100 mug) and diphenylpyraline (100 and 200mug). Pretreatment with the histamine H2-receptor antagonist metiamide (100 and 200 mug i.c.v.) failed to modify either of the responses. A dose-related antagonism of the hypertensive response to histamine i.c.v. was elicited by phentolamine (100 and 200 mug i.c.v.) but the positive chronotropic effect was not modified by this pretreatment. The cardiovascular responses to histamine i.c.v. were abolished by mecamylamine (5.0 mg/kg i.v.) and greatly reduced by 6-hydroxydopamine (3 X 250 mug i.c.v.), but only the tachycardia was significantly modified by atropine (100 mug i.c.v.) and propranolol (1 mg/kg i.v.). Propranolol (100 mug i.c.v.), bilateral vagotomy, or acute bilateral adrenal demedullation failed to modify the cardiovascular responses to histamine i.c.v. The results suggest that histamine is able to modify the resting blood pressure and heart rate by independent central modes of action, which involve central adrenergic and cholinergic mechanisms. | The cardiovascular effects of intraventricularly administered histamine in the anaesthetised rat. In urethane-anaestetised rats intraventricular (i.c.v.) injections of histamine (0.1-10.0mug) elicited dose-related rises in both the resting blood pressure and heart rate. These cardiovascular effects of histamine were antagonised in a dose-dependent manner by i.c.v. pretreatments with the histamine H1-receptor antagonists mepyramine (10, 50 and 100 mug) and diphenylpyraline (100 and 200mug). Pretreatment with the histamine H2-receptor antagonist metiamide (100 and 200 mug i.c.v.) failed to modify either of the responses. A dose-related antagonism of the hypertensive response to histamine i.c.v. was elicited by phentolamine (100 and 200 mug i.c.v.) but the positive chronotropic effect was not modified by this pretreatment. The cardiovascular responses to histamine i.c.v. were abolished by mecamylamine (5.0 mg/kg i.v.) and greatly reduced by 6-hydroxydopamine (3 X 250 mug i.c.v.), but only the tachycardia was significantly modified by atropine (100 mug i.c.v.) and propranolol (1 mg/kg i.v.). Propranolol (100 mug i.c.v.), bilateral vagotomy, or acute bilateral adrenal demedullation failed to modify the cardiovascular responses to histamine i.c.v. The results suggest that histamine is able to modify the resting blood pressure and heart rate by independent central modes of action, which involve central adrenergic and cholinergic mechanisms. | [
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PMID:8736 | The haemolytic effect of phallolysin. | Phallolysin from the toadstool, Amanita phalloides, is a basic protein that causes direct haemolysis of red cells. The dose-response curve is steep; the pH optimum is in the weakly acid range. The rate of haemolysis increases with the concentration of the lysin, the optimal temperature is 20 degrees C. The percentage haemolysis-time curves are S-shaped. Haemolysis is of the non-osmotic type. Ca2+ is not required but inhibits haemolysis in a concentration-dependent fashion, as do Mg2+ and Zn2+. The red cell sensitivity of various animal species decreases in the following sequence:mouse greater than rabbit = guniea pig greater than rat greater than man greater than dog approximately or equal to pig greater than sheep = cattle. Red cells of cattle and sheep are largely resistant. Phallolysin is virtually not consumed on haemalysis: the amount of haemoglobin released increases with the number of red cells applied; on repeated addition of fresh red cells the haemolysate retains its full activity. Phallolysin is not inhibited by serum, albumin, cholesterol, lecithin, cephalin or sphingomyelin; inhibition by red cell ghosts of phallolysin haemolysis is considerably less than that of digitonin haemolysis. At sublytic concentrations phallolysin, unlike benzalkonium chloride, liberates practically no membrane lipids from human red cells. Surface activity of phallolysin does not exceed that of bovine serum albumin.-A saponin-like interaction with cholesterol as the basic mechanism of haemolysis can be disregarded. There is also no evidence suggesting a detergent-like effect. | The haemolytic effect of phallolysin. Phallolysin from the toadstool, Amanita phalloides, is a basic protein that causes direct haemolysis of red cells. The dose-response curve is steep; the pH optimum is in the weakly acid range. The rate of haemolysis increases with the concentration of the lysin, the optimal temperature is 20 degrees C. The percentage haemolysis-time curves are S-shaped. Haemolysis is of the non-osmotic type. Ca2+ is not required but inhibits haemolysis in a concentration-dependent fashion, as do Mg2+ and Zn2+. The red cell sensitivity of various animal species decreases in the following sequence:mouse greater than rabbit = guniea pig greater than rat greater than man greater than dog approximately or equal to pig greater than sheep = cattle. Red cells of cattle and sheep are largely resistant. Phallolysin is virtually not consumed on haemalysis: the amount of haemoglobin released increases with the number of red cells applied; on repeated addition of fresh red cells the haemolysate retains its full activity. Phallolysin is not inhibited by serum, albumin, cholesterol, lecithin, cephalin or sphingomyelin; inhibition by red cell ghosts of phallolysin haemolysis is considerably less than that of digitonin haemolysis. At sublytic concentrations phallolysin, unlike benzalkonium chloride, liberates practically no membrane lipids from human red cells. Surface activity of phallolysin does not exceed that of bovine serum albumin.-A saponin-like interaction with cholesterol as the basic mechanism of haemolysis can be disregarded. There is also no evidence suggesting a detergent-like effect. | [
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PMID:8737 | Desensitization of kitten atria to chronotropic, inotropic and adenylyl cyclase stimulating effects of (-)isoprenaline. | Desensitization of kitten atria with 30muM (-)isoprenaline resulted in a 6-fold and 15-fold increase in the EC50's of (-)isoprenaline for its positive chronotropic effects (sinus pacemakers) and positive inotropic effects (left atria), respectively, but only in a 2-fold increase of the EC50 of (-)isoprenaline for adenylyl cyclase stimulation in membrane particles from atria. However, maximum cyclase stimulation by (-)isoprenaline was decreased to 1/2 in membranes from (-)isoprenaline-treated atria, whereas maximum increases in rate of sinus pacemakers and force of left atria were unchanged and reduced by 15%, respectively. The high affinity beta-adrenoceptor blocker (-)bupranolol antagonized the adenylyl cyclase stimulation by (-)isoprenaline to similar extent in membranes from (-)isoprenaline and untreated atria, suggesting that the apparent affinity of beta-adrenoceptors for ligands is unchanged by desensitization. The evidence is compatible with the concept that desensitization is associated with decreased availability of receptors and with the view that near maximal positive chronotropic effects of catecholamines may be caused by only threshold increases in membrane adenylyl cyclase activity. | Desensitization of kitten atria to chronotropic, inotropic and adenylyl cyclase stimulating effects of (-)isoprenaline. Desensitization of kitten atria with 30muM (-)isoprenaline resulted in a 6-fold and 15-fold increase in the EC50's of (-)isoprenaline for its positive chronotropic effects (sinus pacemakers) and positive inotropic effects (left atria), respectively, but only in a 2-fold increase of the EC50 of (-)isoprenaline for adenylyl cyclase stimulation in membrane particles from atria. However, maximum cyclase stimulation by (-)isoprenaline was decreased to 1/2 in membranes from (-)isoprenaline-treated atria, whereas maximum increases in rate of sinus pacemakers and force of left atria were unchanged and reduced by 15%, respectively. The high affinity beta-adrenoceptor blocker (-)bupranolol antagonized the adenylyl cyclase stimulation by (-)isoprenaline to similar extent in membranes from (-)isoprenaline and untreated atria, suggesting that the apparent affinity of beta-adrenoceptors for ligands is unchanged by desensitization. The evidence is compatible with the concept that desensitization is associated with decreased availability of receptors and with the view that near maximal positive chronotropic effects of catecholamines may be caused by only threshold increases in membrane adenylyl cyclase activity. | [
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PMID:8738 | The comparison of aminotransferase activities in normal and Guerin epithelioma bearing rats. | The activities of 13 aminotransferawes in Guerin epithelioma and in the liver of normal and tumor bearing rats were investigated. Alanine and aspartate aminotransferases show the highest activity in all investigated tissues. In the liver of normal rats high arginine, tyrosine and phenylalanine aminotransferase activities were found. In tumor tissue high level of branched chain amino acid (leucine, valine and isoleucine) aminotransferases were observed. Increase in aminotransferase activities in the liver of tumor bearing rats was found. In order to elucidate the mechanism of this increase an inductive effect of hydrocortisone and protein free extract of tumor tissue on liver aminotransferases has been investigated. The tumor extract did not exert an inductive action. An inductive effect of hydrocortisone was not identical with the change in aminotransferase activities observed in the liver of tumor bearing rats. | The comparison of aminotransferase activities in normal and Guerin epithelioma bearing rats. The activities of 13 aminotransferawes in Guerin epithelioma and in the liver of normal and tumor bearing rats were investigated. Alanine and aspartate aminotransferases show the highest activity in all investigated tissues. In the liver of normal rats high arginine, tyrosine and phenylalanine aminotransferase activities were found. In tumor tissue high level of branched chain amino acid (leucine, valine and isoleucine) aminotransferases were observed. Increase in aminotransferase activities in the liver of tumor bearing rats was found. In order to elucidate the mechanism of this increase an inductive effect of hydrocortisone and protein free extract of tumor tissue on liver aminotransferases has been investigated. The tumor extract did not exert an inductive action. An inductive effect of hydrocortisone was not identical with the change in aminotransferase activities observed in the liver of tumor bearing rats. | [
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PMID:8739 | [Etiology of cerebral vasospasm]. | Basing on prior investigations, the site of action of an alpha-adrenergic substance liberated by platelets, which elicit cerebral vasospasm, was precisely located experimentally in white mice. It could be shown, that this substance incites the alpha-receptors of the smooth muscle cells, because the depletion of catecholamines in the postsynaptic nervous fibres by Tyramine does not abolish the capability for cerebral vasospasm. Furthermore could be shown, that stimulation of beta-receptors by Isoproterenol can inhibit the vasospasm completely. | [Etiology of cerebral vasospasm]. Basing on prior investigations, the site of action of an alpha-adrenergic substance liberated by platelets, which elicit cerebral vasospasm, was precisely located experimentally in white mice. It could be shown, that this substance incites the alpha-receptors of the smooth muscle cells, because the depletion of catecholamines in the postsynaptic nervous fibres by Tyramine does not abolish the capability for cerebral vasospasm. Furthermore could be shown, that stimulation of beta-receptors by Isoproterenol can inhibit the vasospasm completely. | [
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PMID:8741 | Involvement of catecholaminergic and cholinergic mechanisms in the pulsatile release of LH in the long-term ovariectomized rat. | In the long-term ovariectomized rat the secretion of LH has a pulsatile character. In such rats no difference was observed between morning and afternoon LH secretion. The administration of phenoxybenzamine, an chi-adrenergic blocker, resulted in depressed plasma LH levels. chi-Methyl-tyrosine (chi-MT), an inhibitor of tyrosine hydroxylase had no effect on plasma LH levels, whereas bis(4methyl-1-homopiperazinil-thiocarbonil) disulphide (FLA 63), an inhibitor of dopaminic-beta-hydroxylase, induced decreased plasma LH levels and disappearance of the pulsations. The same effect was observed after the administration of apomorphine, a dopaminic receptor stimulating drug, whereas the administration of 1-hydroxy-3-amino-pyrrolidone-2 (HA-966), which blocks dopamine release, significantly raised plasma LH levels. Scopolamine, a cholinergic muscarinic receptor blocking drug, had no effect on plasma LH levels, whereas mecamylamine, a cholinergic nicotine receptor blocking agent, decreased them. These results are consistent with the hypothesis that the pulsatile release of LH in the long-term ovariectomized rat is caused by the stimulating activity of adrenergic and cholinergic, probably nicotinic, systems and the inhibitory activity of a dopaminergic system. | Involvement of catecholaminergic and cholinergic mechanisms in the pulsatile release of LH in the long-term ovariectomized rat. In the long-term ovariectomized rat the secretion of LH has a pulsatile character. In such rats no difference was observed between morning and afternoon LH secretion. The administration of phenoxybenzamine, an chi-adrenergic blocker, resulted in depressed plasma LH levels. chi-Methyl-tyrosine (chi-MT), an inhibitor of tyrosine hydroxylase had no effect on plasma LH levels, whereas bis(4methyl-1-homopiperazinil-thiocarbonil) disulphide (FLA 63), an inhibitor of dopaminic-beta-hydroxylase, induced decreased plasma LH levels and disappearance of the pulsations. The same effect was observed after the administration of apomorphine, a dopaminic receptor stimulating drug, whereas the administration of 1-hydroxy-3-amino-pyrrolidone-2 (HA-966), which blocks dopamine release, significantly raised plasma LH levels. Scopolamine, a cholinergic muscarinic receptor blocking drug, had no effect on plasma LH levels, whereas mecamylamine, a cholinergic nicotine receptor blocking agent, decreased them. These results are consistent with the hypothesis that the pulsatile release of LH in the long-term ovariectomized rat is caused by the stimulating activity of adrenergic and cholinergic, probably nicotinic, systems and the inhibitory activity of a dopaminergic system. | [
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PMID:8742 | Chronic treatment with reserpine and adrenocortical activation. | Daily i.p. injection of reserpine for 9 days strongly depletes hypothalamic norephinephrine (NE); after an initial activation, adrenocortical function returns to control values by the 5th day. Tyrosine hydroxylase (TH) activity in the brain stem of reserpine-treated rats exhibits a progressive increase. Alpha-methyl-para-tyrosine (chi-MpT) in rats chronically pretreated with reserpine provokes adrenocortical activation and a further decrease of hypothalamic NE. Exogenous ACTH in the same animals revealed an unimpaired adrenocortical reactivity after prolonged treatment with reserpine. These results seem to suggest that the disappearance of adrenocortical activation following long-term treatment with reserpine is due to the stimulated formation of a small functional pool of NE available for the tonic inhibition of CRF-ACTH secretion. | Chronic treatment with reserpine and adrenocortical activation. Daily i.p. injection of reserpine for 9 days strongly depletes hypothalamic norephinephrine (NE); after an initial activation, adrenocortical function returns to control values by the 5th day. Tyrosine hydroxylase (TH) activity in the brain stem of reserpine-treated rats exhibits a progressive increase. Alpha-methyl-para-tyrosine (chi-MpT) in rats chronically pretreated with reserpine provokes adrenocortical activation and a further decrease of hypothalamic NE. Exogenous ACTH in the same animals revealed an unimpaired adrenocortical reactivity after prolonged treatment with reserpine. These results seem to suggest that the disappearance of adrenocortical activation following long-term treatment with reserpine is due to the stimulated formation of a small functional pool of NE available for the tonic inhibition of CRF-ACTH secretion. | [
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PMID:8740 | [Statistical analysis of cerebrospinal fluid acid-base equilibrium and cerebrospinal fluid lactate concentration in cases of brain tumors, cerebrocranial injuries and meningoencephalitis]. | A statistical analysis of CSF lactate concentration and CSF pH and PCO2 was performed. The values were obtained from 211 samples taken from 76 neurosurgical patients. The values of pH and pCO2 were classified in three groups corresponding to the following three ranges of lactate concentration: below 15 mg%, 15-30 mg%, over 30 mg%. The mean values and standard deviations were calculated: suitable tests: F, t (Student), C (Cochran and Cox) were used. It was established, that statistically significant changes of CSF acid-base balance were present at lactate levels over 30 mg%. Next, the patients with lactate concentrations over 30 mg% were analysed. They were divided into three groups according to etiology: inflammatory changes, injuries, tumours. It was shown, that the CSF acid-base balance in patients with brain tumours is less disturbed then in patients with inflammatory changes or brain injury. | [Statistical analysis of cerebrospinal fluid acid-base equilibrium and cerebrospinal fluid lactate concentration in cases of brain tumors, cerebrocranial injuries and meningoencephalitis]. A statistical analysis of CSF lactate concentration and CSF pH and PCO2 was performed. The values were obtained from 211 samples taken from 76 neurosurgical patients. The values of pH and pCO2 were classified in three groups corresponding to the following three ranges of lactate concentration: below 15 mg%, 15-30 mg%, over 30 mg%. The mean values and standard deviations were calculated: suitable tests: F, t (Student), C (Cochran and Cox) were used. It was established, that statistically significant changes of CSF acid-base balance were present at lactate levels over 30 mg%. Next, the patients with lactate concentrations over 30 mg% were analysed. They were divided into three groups according to etiology: inflammatory changes, injuries, tumours. It was shown, that the CSF acid-base balance in patients with brain tumours is less disturbed then in patients with inflammatory changes or brain injury. | [
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PMID:8743 | Nicotinic acid in the treatment of schizophrenias. Practical and theoretical considerations. | After reviewing the literature on nicotinic acid in the treatment of schizophrenia, the authors present the results of the Canadian collaborative study. The data indicate that nicotinic acid has no therapeutic effect of schizophrenia. | Nicotinic acid in the treatment of schizophrenias. Practical and theoretical considerations. After reviewing the literature on nicotinic acid in the treatment of schizophrenia, the authors present the results of the Canadian collaborative study. The data indicate that nicotinic acid has no therapeutic effect of schizophrenia. | [
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PMID:8744 | Rebound phenomena in manic patients following physostigmine. Preliminary observations. | The authors have administered physostigmine intravenously to three hospitalized manic patients on a double-blind basis. All three individuals showed clinical change both during and after the physostigmine period, which can be clearly delineated into three distinct phases. The behavioral modifications occurring during the physostigmine run did not qualitatively alter the underlying mania. The authors focus on 'rebound' phenomena, or post-physostigmine changes, as a possible clinical index with which chemically to characterize the initial state of amine imbalance responsible for a given affective illness. The data are considered consistent with an adrenergic-dopaminergic-cholinergic balance hypothesis of affective disorders, and may provide a relevant link in understanding the interface or crossover between manic and schizo-affective illness. | Rebound phenomena in manic patients following physostigmine. Preliminary observations. The authors have administered physostigmine intravenously to three hospitalized manic patients on a double-blind basis. All three individuals showed clinical change both during and after the physostigmine period, which can be clearly delineated into three distinct phases. The behavioral modifications occurring during the physostigmine run did not qualitatively alter the underlying mania. The authors focus on 'rebound' phenomena, or post-physostigmine changes, as a possible clinical index with which chemically to characterize the initial state of amine imbalance responsible for a given affective illness. The data are considered consistent with an adrenergic-dopaminergic-cholinergic balance hypothesis of affective disorders, and may provide a relevant link in understanding the interface or crossover between manic and schizo-affective illness. | [
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PMID:8745 | Schedule of protein ingestion and circadian rhythm of certain hepatic enzyme activities involved in glucose metabolism in the rat. | The circadian rhythms of liver glycogen, plasma glucose, corticosterone and insulin, and hepatic activity of PK, G6PDH, ME, Ac, CoA carbox. PEP-CK and GPT were studied in adult rats. Animals either received a mixed diet ad libitum (8% protein) or a protein meal (1.1 g protein) given at 05:00 or 17:00 h, with free access to a protein-free diet (separately fed). When the protein meal was ingested during the lighted period (17:00) the 24-hour average level of liver PEP-CK was greater than in rats consuming protein during darkness (05:00). In the latter case, modification of the circadian rhythm of liver glycogen and of circadian rhythm of liver PK, G6PDH, ME and Ac.CoA carbox. activity (increase of 24 h average level, extension of period of high activity, sudden increase after ingestion of protein meal) were observed. Conversely, the circadian rhythm of plasma insulin and corticosterone and of liver PEP-CK and GPT activity were only slightly affected by the mode of feeding. | Schedule of protein ingestion and circadian rhythm of certain hepatic enzyme activities involved in glucose metabolism in the rat. The circadian rhythms of liver glycogen, plasma glucose, corticosterone and insulin, and hepatic activity of PK, G6PDH, ME, Ac, CoA carbox. PEP-CK and GPT were studied in adult rats. Animals either received a mixed diet ad libitum (8% protein) or a protein meal (1.1 g protein) given at 05:00 or 17:00 h, with free access to a protein-free diet (separately fed). When the protein meal was ingested during the lighted period (17:00) the 24-hour average level of liver PEP-CK was greater than in rats consuming protein during darkness (05:00). In the latter case, modification of the circadian rhythm of liver glycogen and of circadian rhythm of liver PK, G6PDH, ME and Ac.CoA carbox. activity (increase of 24 h average level, extension of period of high activity, sudden increase after ingestion of protein meal) were observed. Conversely, the circadian rhythm of plasma insulin and corticosterone and of liver PEP-CK and GPT activity were only slightly affected by the mode of feeding. | [
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PMID:8748 | The antihypertensive action of several beta-adrenoreceptor-blocking drugs. | The antihypertensive and pulse-slowing effects of racemic propranolol, oxprenolol, pindolol, practolol and d-propranolol were assessed in 54 hypertensive patients. Drug dosage was selected to be proportionate to beta-adrenoreceptor-blocking potency; d-propranolol dosage equalled approximately that of racemic propranolol. D-propranolol had onlyslight antihypertensive effect; the four other drugs were found to have a considerable and approximately equal antihypertensive effect. The degree of slowing of heart rate varied with the different drugs, being greatest with racemic propanolol. The effect on pulse rate did not correlate with the effect on blood pressure for most of the drugs. The falls in blood pressure induced by racemic propanolol were strongly correlated with those induced by each of the other drugs. The small falls in blood pressured induced by d-propranolol correlated also with those induced by practolol (which had no membrane activity) and are presumably due to its weak beta-adrenoreceptor-blocking action. The beta-adrenoreceptor-blocking action per se is responsible for the antihypertensive action of these drugs. | The antihypertensive action of several beta-adrenoreceptor-blocking drugs. The antihypertensive and pulse-slowing effects of racemic propranolol, oxprenolol, pindolol, practolol and d-propranolol were assessed in 54 hypertensive patients. Drug dosage was selected to be proportionate to beta-adrenoreceptor-blocking potency; d-propranolol dosage equalled approximately that of racemic propranolol. D-propranolol had onlyslight antihypertensive effect; the four other drugs were found to have a considerable and approximately equal antihypertensive effect. The degree of slowing of heart rate varied with the different drugs, being greatest with racemic propanolol. The effect on pulse rate did not correlate with the effect on blood pressure for most of the drugs. The falls in blood pressure induced by racemic propanolol were strongly correlated with those induced by each of the other drugs. The small falls in blood pressured induced by d-propranolol correlated also with those induced by practolol (which had no membrane activity) and are presumably due to its weak beta-adrenoreceptor-blocking action. The beta-adrenoreceptor-blocking action per se is responsible for the antihypertensive action of these drugs. | [
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PMID:8749 | A double blind study of the antidepressants dibenzepin (Noveril) and amitriptyline. | The study undertook to compare the efficacy of dibenzepin and amitriptyline in the treatment of endogenous depression. The outcome of the study was that both drugs appear to be equally effective in the treatment of depression, but dibenzepin was more efficient in reducing associated anxiety. Both drugs are appropriate to the treatment of psychotic depression, and work equally rapid. There was also a tendency for dibenzepin to elicit less intense side effects. | A double blind study of the antidepressants dibenzepin (Noveril) and amitriptyline. The study undertook to compare the efficacy of dibenzepin and amitriptyline in the treatment of endogenous depression. The outcome of the study was that both drugs appear to be equally effective in the treatment of depression, but dibenzepin was more efficient in reducing associated anxiety. Both drugs are appropriate to the treatment of psychotic depression, and work equally rapid. There was also a tendency for dibenzepin to elicit less intense side effects. | [
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PMID:8750 | The rational use of anxiolytics. | The prescribing of anxiolytics is often a hit-and-miss process. Current knowledge is examined to encourage a more rational use of such drugs. Because the common symptoms occur in a great array of illnesses, diagnosis is of first importance. For the transient situational disturbance drugs may be unnecessary or may be used merely for a day or two. If the anxiety state persists for a month or so the illness might be termed an anxiety neurosis and if there is no accompanying depression, a short course of benzodiazepine may be of value. With depression present to more than a mild degree as part of the neurosis the tricyclic antidepressant doxepin usually achieves better results than a benzodiazepine. Imipramine can be helpful for the phobic anxiety syndrome and monoamine-oxidase inhibitors can be of separate utility. If the anxiety and depression occur in the context of alcoholism, thioridazine and amitriptyline have certain advantages. There is very little place for phenothiazines or other antipsychotic agents in low doses in the therapy of anxiety except for thioridazine in the above indication. | The rational use of anxiolytics. The prescribing of anxiolytics is often a hit-and-miss process. Current knowledge is examined to encourage a more rational use of such drugs. Because the common symptoms occur in a great array of illnesses, diagnosis is of first importance. For the transient situational disturbance drugs may be unnecessary or may be used merely for a day or two. If the anxiety state persists for a month or so the illness might be termed an anxiety neurosis and if there is no accompanying depression, a short course of benzodiazepine may be of value. With depression present to more than a mild degree as part of the neurosis the tricyclic antidepressant doxepin usually achieves better results than a benzodiazepine. Imipramine can be helpful for the phobic anxiety syndrome and monoamine-oxidase inhibitors can be of separate utility. If the anxiety and depression occur in the context of alcoholism, thioridazine and amitriptyline have certain advantages. There is very little place for phenothiazines or other antipsychotic agents in low doses in the therapy of anxiety except for thioridazine in the above indication. | [
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PMID:8752 | Fractures of the foot in children. | Fractures of the foot in children are less common than in adults and are due to severe trauma in which associated injuries may take precedence. Disturbances of growth can occur, usually when there is associated soft tissue damage. Because remodeling of the long bones of the foot does not always correct marked displacement, adequate reduction should be sought to prevent subsequent foot discomfort. Open fractures of the foot deserve considerable care. Primary closure of the wounds should be avoided. | Fractures of the foot in children. Fractures of the foot in children are less common than in adults and are due to severe trauma in which associated injuries may take precedence. Disturbances of growth can occur, usually when there is associated soft tissue damage. Because remodeling of the long bones of the foot does not always correct marked displacement, adequate reduction should be sought to prevent subsequent foot discomfort. Open fractures of the foot deserve considerable care. Primary closure of the wounds should be avoided. | [
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PMID:8755 | Spectrophotometric characteristics of bilirubin. | Spectrophotometric characteristics of bilirubin at low concentrations (0.005-2.500 mg/100 ml) have been studied under various physical conditions in order to gain a better understanding of the state of bilirubin when preparing "solutions" for laboratory use. Standing, minimal shaking, or stirring of the bilirubin preparations at pH 7.4 progressively reduced and altered the maximal spectral absorption of bilirubin (440 nm) in aqueous buffered media. The shift to 415-420 nm is attributed to oxidation of the pigment whereas shoulder formation is attributed to the formation of large size particles (flocculants). In the presence of antixidants (L-ascorbic acid and nitrogen gas) and EDTA the maximal absorption peak remained at 440 nm but decreased in magnitude concomitant with development of progressively increasing shoulder at 480-560 nm. In the absence of antioxidants and EDTA maximal absorption shifted to 415-420 nm and the magnitude of 480-560 nm shoulder formation was less. At the higher concentrations of bilirubin and with reduction in pH of the buffer in the absence of antioxidants, the shift to lower wave lengths was reduced and 450-560 nm shoulder formation was increased. In the absence of antioxidants and EDTA at the lower concentrations of bilirubin and in more alkaline media, the reduction at 440 nm and the shift of maximal absorption to the shorter wave lengths was enhanced. At pH 12, stirring of antioxidant-EDTA-containing solutions of bilirubin resulted in neither a shift of maximal absorption to the shorter wave lengths nor the formation of 480-560 nm shoulder. The formation of 480-560 nm shoulder was accompanied by the visual appearance of turbidity. The formation of flocculants when a "solution" is agitated indicates that significant portions of the pigment were in fact, not in solution and must have existed previously as a finely dispersed colloidal sol or supersaturated solution which progressed to a colloidal sol. Spectral curves of bilirubin, therefore, may represent a composite resulting from four physical states of bilirubin: (1) bilirubin truly in solution with the spectral peak at 440 nm; (2) bilirubin in the fine colloidal dispersion with spectral characteristics similar to those of bilirubin in solution; (3) bilirubin flocculant giving 480-560 nm shoulder; and (4) oxidation products of bilirubin with the spectral peaks lower than 440 nm. Increasing the pH of the aqueous media containing bilirubin (0.05 mg/100 ml) from 7.4 to 12.0 increased the molar extinction coefficient of bilirubin, E1M/440 1cm, progressively to a maximum at pH 12 of 6.35 X 10(4). Very dilute bilirubin preparations (0.005-0.050 mg/100 ml) in aqueous media, pH 7.4, exhibited spectral evidence of rapid oxidation (more so at higher pH), but spectral shoulder formation was still observed after mechanical agitation. Thus, the solubility of bilirubin in 0.1 M phosphate buffer at pH 7.4 appears to be less than 0.005 mg/100 ml. | Spectrophotometric characteristics of bilirubin. Spectrophotometric characteristics of bilirubin at low concentrations (0.005-2.500 mg/100 ml) have been studied under various physical conditions in order to gain a better understanding of the state of bilirubin when preparing "solutions" for laboratory use. Standing, minimal shaking, or stirring of the bilirubin preparations at pH 7.4 progressively reduced and altered the maximal spectral absorption of bilirubin (440 nm) in aqueous buffered media. The shift to 415-420 nm is attributed to oxidation of the pigment whereas shoulder formation is attributed to the formation of large size particles (flocculants). In the presence of antixidants (L-ascorbic acid and nitrogen gas) and EDTA the maximal absorption peak remained at 440 nm but decreased in magnitude concomitant with development of progressively increasing shoulder at 480-560 nm. In the absence of antioxidants and EDTA maximal absorption shifted to 415-420 nm and the magnitude of 480-560 nm shoulder formation was less. At the higher concentrations of bilirubin and with reduction in pH of the buffer in the absence of antioxidants, the shift to lower wave lengths was reduced and 450-560 nm shoulder formation was increased. In the absence of antioxidants and EDTA at the lower concentrations of bilirubin and in more alkaline media, the reduction at 440 nm and the shift of maximal absorption to the shorter wave lengths was enhanced. At pH 12, stirring of antioxidant-EDTA-containing solutions of bilirubin resulted in neither a shift of maximal absorption to the shorter wave lengths nor the formation of 480-560 nm shoulder. The formation of 480-560 nm shoulder was accompanied by the visual appearance of turbidity. The formation of flocculants when a "solution" is agitated indicates that significant portions of the pigment were in fact, not in solution and must have existed previously as a finely dispersed colloidal sol or supersaturated solution which progressed to a colloidal sol. Spectral curves of bilirubin, therefore, may represent a composite resulting from four physical states of bilirubin: (1) bilirubin truly in solution with the spectral peak at 440 nm; (2) bilirubin in the fine colloidal dispersion with spectral characteristics similar to those of bilirubin in solution; (3) bilirubin flocculant giving 480-560 nm shoulder; and (4) oxidation products of bilirubin with the spectral peaks lower than 440 nm. Increasing the pH of the aqueous media containing bilirubin (0.05 mg/100 ml) from 7.4 to 12.0 increased the molar extinction coefficient of bilirubin, E1M/440 1cm, progressively to a maximum at pH 12 of 6.35 X 10(4). Very dilute bilirubin preparations (0.005-0.050 mg/100 ml) in aqueous media, pH 7.4, exhibited spectral evidence of rapid oxidation (more so at higher pH), but spectral shoulder formation was still observed after mechanical agitation. Thus, the solubility of bilirubin in 0.1 M phosphate buffer at pH 7.4 appears to be less than 0.005 mg/100 ml. | [
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PMID:8756 | Prolonged pneumococcal meningitis due to an organism with increased resistance to penicillin. | For more than 30 years, penicillin has been the agent of choice for pneumococcal infections. During this time the majority of strains of Streptococcus pneumoniae have been highly susceptible to penicillin. However, during the last ten years there have been sporadic reports of pneumococci with increased resistance to penicillin. The case report of an 18-month-old white boy with meningitis due to a strain of S. pneumoniae with increased resistance to penicillin is presented. The MIC of the organism to penicillin was 0.2 mug/ml and the MBC 0.39 mug/ml. The patient had normal immunity and no demonstrable sequestered focus of infection but failed to respond to appropriate doses of intravenous penicillin. Treatment with chloramphenicol caused a dramatic bacteriologic and clinical response. This experience reemphasizes the existence of pneumococcal strains of intermediate penicillin sensitivity and the importance of in vitro susceptibility tests. | Prolonged pneumococcal meningitis due to an organism with increased resistance to penicillin. For more than 30 years, penicillin has been the agent of choice for pneumococcal infections. During this time the majority of strains of Streptococcus pneumoniae have been highly susceptible to penicillin. However, during the last ten years there have been sporadic reports of pneumococci with increased resistance to penicillin. The case report of an 18-month-old white boy with meningitis due to a strain of S. pneumoniae with increased resistance to penicillin is presented. The MIC of the organism to penicillin was 0.2 mug/ml and the MBC 0.39 mug/ml. The patient had normal immunity and no demonstrable sequestered focus of infection but failed to respond to appropriate doses of intravenous penicillin. Treatment with chloramphenicol caused a dramatic bacteriologic and clinical response. This experience reemphasizes the existence of pneumococcal strains of intermediate penicillin sensitivity and the importance of in vitro susceptibility tests. | [
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PMID:8759 | An exploratory investigation of the personality correlates of aging using the Hand Test. | The Hand Test was administered to 27 older adults of both sexes (Mage = 66.56) to investigate possible changes in personality concomitant with normal aging. To control partially for such factors as cultural influences and intelligence differences a matched-pair design was used in which the test protocols of the older adults were matched with those of their children of the same sex (Mage = 36.44). Though the Hand Test has not been independently validated on older adults, results were consistent with past findings using projective techniques inasmuch as depletion and constriction of personality were noted. Criticisms of research on the clinical assessment of the elderly were discussed. | An exploratory investigation of the personality correlates of aging using the Hand Test. The Hand Test was administered to 27 older adults of both sexes (Mage = 66.56) to investigate possible changes in personality concomitant with normal aging. To control partially for such factors as cultural influences and intelligence differences a matched-pair design was used in which the test protocols of the older adults were matched with those of their children of the same sex (Mage = 36.44). Though the Hand Test has not been independently validated on older adults, results were consistent with past findings using projective techniques inasmuch as depletion and constriction of personality were noted. Criticisms of research on the clinical assessment of the elderly were discussed. | [
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PMID:8760 | H in cortical peritubular capillaries of rat kidney. | The pH of peritubular capillaries was measured by means of antimony microelectrodes, during their perfusion with mammalian Ringer's solutions at different pH, in control and acetazolamide infused rats. In capillaries perfused with a solution more acid than blood, significant alkalinization was observed at increasing distances from the point of perfusion, while during perfusions with more alkaline solutions, acidification was observed. Plotting the pH change observed per micrometer of distance from the perfusion point against the pH of the perfusing solution, the pH in equilibrium with tubular cells was interpolated. A value of 7.51 +/- 0.01 was found for control rats, significantly higher than the mean arterial blood pH of this group, of 7.39. In acetazolamide infused rats an equilibrium pH of 7.44 +/- 0.02 was found, still higher than the blood pH of 7.34. The slope of these lines was significantly greater in control than in acetazolamide treated rats. This slope was shown to evaluate permeability to the ions responsible for acid-base balance. The present data suggest that peritubular alkalinization is reduced after carbonic anhydrase inhibition due to decreased peritubular permeability to the involved ions, which represents a further site of action of these inhibitors. | H in cortical peritubular capillaries of rat kidney. The pH of peritubular capillaries was measured by means of antimony microelectrodes, during their perfusion with mammalian Ringer's solutions at different pH, in control and acetazolamide infused rats. In capillaries perfused with a solution more acid than blood, significant alkalinization was observed at increasing distances from the point of perfusion, while during perfusions with more alkaline solutions, acidification was observed. Plotting the pH change observed per micrometer of distance from the perfusion point against the pH of the perfusing solution, the pH in equilibrium with tubular cells was interpolated. A value of 7.51 +/- 0.01 was found for control rats, significantly higher than the mean arterial blood pH of this group, of 7.39. In acetazolamide infused rats an equilibrium pH of 7.44 +/- 0.02 was found, still higher than the blood pH of 7.34. The slope of these lines was significantly greater in control than in acetazolamide treated rats. This slope was shown to evaluate permeability to the ions responsible for acid-base balance. The present data suggest that peritubular alkalinization is reduced after carbonic anhydrase inhibition due to decreased peritubular permeability to the involved ions, which represents a further site of action of these inhibitors. | [
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PMID:8761 | Physostigmine-induced contractures in frog skeletal muscle. | Physostigmine in 15 mM concentration at pH 8.4 produces reversible contractures of up to 0.3 Po tension output in frog's whole toe muscle or in 7-10 fiber bundles of these muscles, At pH 7.2, the 15 mM physostigmine contracture output is only about 0.10 Po. The 15 mM, pH 8.4 contractures are essentially unaffected by lack of external Ca2+, complete depolarization of the fibers, detubulation by glycerol treatment, and 0 degrees C ambient temperature. These results and other evidence indicate that physostigmine produces contracture by directly releasing activator Ca2+ from the sarcoplasmic reticulum (SR). Pretreatment of muscles with 4 mM procaine reduces physostigmine's capacity to produce contracture, evidently by means of a competitive inhibition at SR sites. The above results indicate similarities between physostagmine and caffeine contractures. But the physostigmine action differs in that it is reversible, and, especially, it lacks the ability, strongly characteristic of caffeine, to sensitize a muscle to produce a rapid cooling contracture. The internal action of physostigmine requires that it be permeant, and, since it is a weak base (pKa = 8.2), this property is provided by its uncharged base. But, once internal, where the pH = 6.8, most of the drug will be protonated and it may act on the SR in this form, in contrast with caffeine which, since its pKa is about 1.0, acts on the SR as uncharged base. | Physostigmine-induced contractures in frog skeletal muscle. Physostigmine in 15 mM concentration at pH 8.4 produces reversible contractures of up to 0.3 Po tension output in frog's whole toe muscle or in 7-10 fiber bundles of these muscles, At pH 7.2, the 15 mM physostigmine contracture output is only about 0.10 Po. The 15 mM, pH 8.4 contractures are essentially unaffected by lack of external Ca2+, complete depolarization of the fibers, detubulation by glycerol treatment, and 0 degrees C ambient temperature. These results and other evidence indicate that physostigmine produces contracture by directly releasing activator Ca2+ from the sarcoplasmic reticulum (SR). Pretreatment of muscles with 4 mM procaine reduces physostigmine's capacity to produce contracture, evidently by means of a competitive inhibition at SR sites. The above results indicate similarities between physostagmine and caffeine contractures. But the physostigmine action differs in that it is reversible, and, especially, it lacks the ability, strongly characteristic of caffeine, to sensitize a muscle to produce a rapid cooling contracture. The internal action of physostigmine requires that it be permeant, and, since it is a weak base (pKa = 8.2), this property is provided by its uncharged base. But, once internal, where the pH = 6.8, most of the drug will be protonated and it may act on the SR in this form, in contrast with caffeine which, since its pKa is about 1.0, acts on the SR as uncharged base. | [
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PMID:8762 | The effect of Ca2+ on the metarhodopsin I-II transition. I. Experiments. | The effect of Ca2+ on kinetics and equilibrium of the Meta I-II transition was studied in rhodopsin-digitonin-solutions using flash-photometry. With increasing Ca2+-concentrations the Meta I-II-equilibrium is shifted to Meta I. The pH-dependence of the Meta I-II equilibrium is suppressed by Ca2+. To obtain the same effect as with bivalent cations about the 10-fold concentration of univalent ions is required. Ca2+-ions have also an effect on the rate of equilibrating Meta I-II: with increasing Ca2+-concentration the rate-constants of the rapid and slow component decrease and become equal to the value at pH8. This observation can be described as an inhibition of the catalytic effect of protons by Ca2+. Similar results are obtained with Mg2+, whereas K+ and Na+ are practically ineffective. In the presence of the Ca2+-blocking agents verapamil (Isoptin) and D-600 the rate of equilibrating Meta I-II is reduced. These and several former observations can be explained by a model in which the Meta I-II transition is coupled with the separation of negative fixed charges, which can be clamped by Ca2+. | The effect of Ca2+ on the metarhodopsin I-II transition. I. Experiments. The effect of Ca2+ on kinetics and equilibrium of the Meta I-II transition was studied in rhodopsin-digitonin-solutions using flash-photometry. With increasing Ca2+-concentrations the Meta I-II-equilibrium is shifted to Meta I. The pH-dependence of the Meta I-II equilibrium is suppressed by Ca2+. To obtain the same effect as with bivalent cations about the 10-fold concentration of univalent ions is required. Ca2+-ions have also an effect on the rate of equilibrating Meta I-II: with increasing Ca2+-concentration the rate-constants of the rapid and slow component decrease and become equal to the value at pH8. This observation can be described as an inhibition of the catalytic effect of protons by Ca2+. Similar results are obtained with Mg2+, whereas K+ and Na+ are practically ineffective. In the presence of the Ca2+-blocking agents verapamil (Isoptin) and D-600 the rate of equilibrating Meta I-II is reduced. These and several former observations can be explained by a model in which the Meta I-II transition is coupled with the separation of negative fixed charges, which can be clamped by Ca2+. | [
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PMID:8763 | The effect of Ca2+ on the metarhodopsin I-II transition. II. Model calculations and hypothesis on a molecular mechanism of visual excitation. | The model for the effect of Ca2+ on the Meta I-II transition (cf. Part I) is formulated quantitatively and in detail. The clamping forces of Ca2+, which shift the equilibrium to the closed MI-conformation, are taken into account in the law of mass action by a higher value for the association constant of Ca2+ with MI than with MII. Thus the main features of the experimental curves of delta MII-absorption-change as a function of Ca2+- and H+-concentration can be reproduced by a few simple association equilibria. The agreement can be improved by calculating with a conformative coupling between two rhodopsin molecules. In a further modification of the model also the observed increase of delta MII in the alkaline beyond pH 9 is reproduced. Finally, the models lead to an opening and closing mechanism for a Ca2+-permeable pore across the disc membrane, thus contributing to a hypothesis of visual excitation. | The effect of Ca2+ on the metarhodopsin I-II transition. II. Model calculations and hypothesis on a molecular mechanism of visual excitation. The model for the effect of Ca2+ on the Meta I-II transition (cf. Part I) is formulated quantitatively and in detail. The clamping forces of Ca2+, which shift the equilibrium to the closed MI-conformation, are taken into account in the law of mass action by a higher value for the association constant of Ca2+ with MI than with MII. Thus the main features of the experimental curves of delta MII-absorption-change as a function of Ca2+- and H+-concentration can be reproduced by a few simple association equilibria. The agreement can be improved by calculating with a conformative coupling between two rhodopsin molecules. In a further modification of the model also the observed increase of delta MII in the alkaline beyond pH 9 is reproduced. Finally, the models lead to an opening and closing mechanism for a Ca2+-permeable pore across the disc membrane, thus contributing to a hypothesis of visual excitation. | [
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PMID:8764 | Further investigations on the effect of denervation and pH on the conductance change at the neuromuscular junction of the frog. | Currents induced by acetylcholine application at the voltage-calmped frog end-plate, were measured over a large range of membrane potentials. Due to a non-linearity of the current-voltage curve, the directly-measured reversal potential may be quite different from the value classically determined by extrapolation (linear regression) of the measurements made at potentials below spike threshold. Denervation and changes of external pH were found to alter the shape of the current-voltage relation, but not the directly-measured reversal potential. These effects are tentatively explained on the basis of changes in the ratio: time-to-peak for [ACh] reaching the receptors/mean life-time of the open synaptic channels. Possible changes in cooperativity are also considered. | Further investigations on the effect of denervation and pH on the conductance change at the neuromuscular junction of the frog. Currents induced by acetylcholine application at the voltage-calmped frog end-plate, were measured over a large range of membrane potentials. Due to a non-linearity of the current-voltage curve, the directly-measured reversal potential may be quite different from the value classically determined by extrapolation (linear regression) of the measurements made at potentials below spike threshold. Denervation and changes of external pH were found to alter the shape of the current-voltage relation, but not the directly-measured reversal potential. These effects are tentatively explained on the basis of changes in the ratio: time-to-peak for [ACh] reaching the receptors/mean life-time of the open synaptic channels. Possible changes in cooperativity are also considered. | [
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PMID:8765 | Force velocity relations in vascular smooth muscle: the influence of pH, pCa, and noradrenaline. | The kinetics of vascular smooth musclw activity was studied by means of afterloaded isotonic contractions of the tetanized rat portal vein at varied pH (8.0-5.9), pCa (3.4-2.1), and during noradrenaline incubation (0.4 mug/ml). Under control conditions (pH 7.3, pCa 2.6) the following parameters of the force velocity relation were calculated: a of Hill's equation (relating to the isometric peak tension) = 0.36; b (relating to the actual muscle length) = 0.19 ML/s; VM Trelating to the actual muscle length) = 0.56 ML/s. Within the range of pCa between 2.0 and 3.2 the amount of force generation (= delta P) depended on the extracellular calcium level whereas the extrapolated velocity of shortening of the unloaded preparation (= VM) did not. Also pH changes between 8.0 and 6.8 as well as noradrenaline incubation at a pH of 5.9 affected delta P quite considerably, but VM only scarcely. At a pH of 6.3, however, VM was distinctly diminished, and a reduced calcium sensitivity of the ATPase was inferred from the shift of ED50 of extracellular calcium from 0.66 mM Ca at a pH of 7.3 to 1.56 mM Ca at a pH of 6.3 (P less than 0.0005). It is concluded from these results that the experimental conditions-pCa between 2.0 and 3.2, pH between 8.0 and 6.8, and noradrenaline added at a pH of 5.9-obviously change the intracellular calcium concentration which influences the number of activated interaction sites rather than the velocity of crossbridge movement. | Force velocity relations in vascular smooth muscle: the influence of pH, pCa, and noradrenaline. The kinetics of vascular smooth musclw activity was studied by means of afterloaded isotonic contractions of the tetanized rat portal vein at varied pH (8.0-5.9), pCa (3.4-2.1), and during noradrenaline incubation (0.4 mug/ml). Under control conditions (pH 7.3, pCa 2.6) the following parameters of the force velocity relation were calculated: a of Hill's equation (relating to the isometric peak tension) = 0.36; b (relating to the actual muscle length) = 0.19 ML/s; VM Trelating to the actual muscle length) = 0.56 ML/s. Within the range of pCa between 2.0 and 3.2 the amount of force generation (= delta P) depended on the extracellular calcium level whereas the extrapolated velocity of shortening of the unloaded preparation (= VM) did not. Also pH changes between 8.0 and 6.8 as well as noradrenaline incubation at a pH of 5.9 affected delta P quite considerably, but VM only scarcely. At a pH of 6.3, however, VM was distinctly diminished, and a reduced calcium sensitivity of the ATPase was inferred from the shift of ED50 of extracellular calcium from 0.66 mM Ca at a pH of 7.3 to 1.56 mM Ca at a pH of 6.3 (P less than 0.0005). It is concluded from these results that the experimental conditions-pCa between 2.0 and 3.2, pH between 8.0 and 6.8, and noradrenaline added at a pH of 5.9-obviously change the intracellular calcium concentration which influences the number of activated interaction sites rather than the velocity of crossbridge movement. | [
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PMID:8766 | pH sensitivity of cells located at the ventrolateral surface of the cat medulla oblongata in vitro. | pH sensitivity of cells located at the ventral surface of the medulla oblongata was examined in a thin brain slice of the cat in vitro and the following results were obtained: (1) Transmembrane potential of the surface cells located in the area medial to the XIIth cranial nerve was reduced slightly by application of low pH solution; (2) In the rostral part of the area medial to the XIIth cranial nerve regular neuronal discharges could be observed extracellularly. The rate of firing of these cells was increased by lowering the external pH. These results were considered to support the idea the H+ receptor cells may exist in the surface layer of the ventral medulla. | pH sensitivity of cells located at the ventrolateral surface of the cat medulla oblongata in vitro. pH sensitivity of cells located at the ventral surface of the medulla oblongata was examined in a thin brain slice of the cat in vitro and the following results were obtained: (1) Transmembrane potential of the surface cells located in the area medial to the XIIth cranial nerve was reduced slightly by application of low pH solution; (2) In the rostral part of the area medial to the XIIth cranial nerve regular neuronal discharges could be observed extracellularly. The rate of firing of these cells was increased by lowering the external pH. These results were considered to support the idea the H+ receptor cells may exist in the surface layer of the ventral medulla. | [
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PMID:8770 | A compact form of double-stranded RNA in solutions containing poly(ethyleneglycol). | Molecules of single-stranded ribosomal RNA and double-stranded replicative form of phage f2 RNA (dsRNA) adopt a compact form in solutions, containing sufficiently high concentrations of salt (NaCl) and polymer (PEG). However, only in the cases of native dsRNA molecules the compact particles are characterized by a regular internal structure, which accounts for the appearance of an intense positive band in CD spectra. Heating or acidification of PEG-containing solutions of dsRNA leads to the disappearance of the intense positive CD band, which results from the "destruction" of the regular internal structure of compact particles. Comparison of properties of DNA and dsRNA compact particles formed in PEG-containing water-salt solutions suggests the existence of similar mechanisms of compactization of double-stranded polynucleotides. | A compact form of double-stranded RNA in solutions containing poly(ethyleneglycol). Molecules of single-stranded ribosomal RNA and double-stranded replicative form of phage f2 RNA (dsRNA) adopt a compact form in solutions, containing sufficiently high concentrations of salt (NaCl) and polymer (PEG). However, only in the cases of native dsRNA molecules the compact particles are characterized by a regular internal structure, which accounts for the appearance of an intense positive band in CD spectra. Heating or acidification of PEG-containing solutions of dsRNA leads to the disappearance of the intense positive CD band, which results from the "destruction" of the regular internal structure of compact particles. Comparison of properties of DNA and dsRNA compact particles formed in PEG-containing water-salt solutions suggests the existence of similar mechanisms of compactization of double-stranded polynucleotides. | [
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PMID:8771 | Protonated polynucleotide structures, 20. Interaction between poly(dG)-poly(dC) and poly(rC).1. | A study of the interaction between poly(dG)-poly(dC) and poly(rC) demonstrates that, at neutral pH and high ionic strength, there is replacement of the dC strand by poly(rC). At acid pH, formation of a triple-stranded complex which equally may involve the replacement phenomenon is observed. There is no evidence for interaction at neutral pH between poly(dG)-poly(dC) and oligo(rC), while a three-stranded complex is formed at acid pH. These data are consistent with the studies of comparative stabilities of double stranded deoxy or ribo polymers and deoxy-ribo hybrids. | Protonated polynucleotide structures, 20. Interaction between poly(dG)-poly(dC) and poly(rC).1. A study of the interaction between poly(dG)-poly(dC) and poly(rC) demonstrates that, at neutral pH and high ionic strength, there is replacement of the dC strand by poly(rC). At acid pH, formation of a triple-stranded complex which equally may involve the replacement phenomenon is observed. There is no evidence for interaction at neutral pH between poly(dG)-poly(dC) and oligo(rC), while a three-stranded complex is formed at acid pH. These data are consistent with the studies of comparative stabilities of double stranded deoxy or ribo polymers and deoxy-ribo hybrids. | [
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PMID:8772 | Affinity labelling of phenylalanyl-tRNA synthetase from E. coli MRE-600 by E. coli tRNAphe containing photoreactive group. | The photoinduced reaction of phenylalanyl-tRNA synthetase (E.C.6.1.1.20) from E.coli MRE-600 with tRNAphe containing photoreative p-N3-C6H4-NHCOCH2-group attached to 4-thiouridine sU8 (azido-tRNAphe) was investigated. The attachment of this group does not influence the dissociation constant of the complex of Phe-tRNAphe with the enzyme, however it results in sevenfold increase of Km in the enzymatic aminoacylation of tRNAphe. Under irradiation at 300 nm at pH 5.8 the covalent binding of [14C]-Phe-azido-tRNAphe to the enzyme takes place 0.3 moles of the reagent being attached per mole of the enzyme. tRNA prevents the reaction. Phenylalanine, ATP,ADP,AMP, adenosine and pyrophosphate (2.5 xx 10(-3) M) don't affect neither the stability of the tRNA-enzyme complex nor the rate of the affinity labelling. The presence of the mixture of either phenylalanine or phenylalaninol with ATP as well as phenylalaninol adenylate exhibits 50% inhibition of the photoinduced reaction. Therefore, the reaction of [14C]-Phe-azido-tRNA with the enzyme is significantly less sensitive to the presence of the ligands than the reaction of chlorambucilyl-tRNA with the reactive group attached to the acceptor end of the tRNA studied in 1. It has been concluded that the kinetics of the affinity labelling does permit to discriminate the influence of the low molecular weight ligands of the enzyme on the different sites of the tRNA enzyme interaction. | Affinity labelling of phenylalanyl-tRNA synthetase from E. coli MRE-600 by E. coli tRNAphe containing photoreactive group. The photoinduced reaction of phenylalanyl-tRNA synthetase (E.C.6.1.1.20) from E.coli MRE-600 with tRNAphe containing photoreative p-N3-C6H4-NHCOCH2-group attached to 4-thiouridine sU8 (azido-tRNAphe) was investigated. The attachment of this group does not influence the dissociation constant of the complex of Phe-tRNAphe with the enzyme, however it results in sevenfold increase of Km in the enzymatic aminoacylation of tRNAphe. Under irradiation at 300 nm at pH 5.8 the covalent binding of [14C]-Phe-azido-tRNAphe to the enzyme takes place 0.3 moles of the reagent being attached per mole of the enzyme. tRNA prevents the reaction. Phenylalanine, ATP,ADP,AMP, adenosine and pyrophosphate (2.5 xx 10(-3) M) don't affect neither the stability of the tRNA-enzyme complex nor the rate of the affinity labelling. The presence of the mixture of either phenylalanine or phenylalaninol with ATP as well as phenylalaninol adenylate exhibits 50% inhibition of the photoinduced reaction. Therefore, the reaction of [14C]-Phe-azido-tRNA with the enzyme is significantly less sensitive to the presence of the ligands than the reaction of chlorambucilyl-tRNA with the reactive group attached to the acceptor end of the tRNA studied in 1. It has been concluded that the kinetics of the affinity labelling does permit to discriminate the influence of the low molecular weight ligands of the enzyme on the different sites of the tRNA enzyme interaction. | [
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PMID:8769 | [Latent renal tubular acidosis of the cirrhotic patient. Study of urinary excretion of protons and sodium]. | Patients suffering from hepatic cirrhosis develop renal tubular acidosis when subjected to an acid overload. This is characterised by a fall in plasma pH and bicarbonate and by inability of the kidney to lower urine pH and to excrete a sufficient quantity of protons in the form of titratable acidy and ammonia. This disturbance is difficult to explain. It may form part of the picture of the classical functional renal insufficiency of the cirrhotic and may be a particular result of altered renal haemodynamics. Detected by the acidification test, this abnormality may be demonstrated in the absence of any other involvement of renal function. The severity of this renal tubular acidosis would appear to be related to the degree of hepatic disease. | [Latent renal tubular acidosis of the cirrhotic patient. Study of urinary excretion of protons and sodium]. Patients suffering from hepatic cirrhosis develop renal tubular acidosis when subjected to an acid overload. This is characterised by a fall in plasma pH and bicarbonate and by inability of the kidney to lower urine pH and to excrete a sufficient quantity of protons in the form of titratable acidy and ammonia. This disturbance is difficult to explain. It may form part of the picture of the classical functional renal insufficiency of the cirrhotic and may be a particular result of altered renal haemodynamics. Detected by the acidification test, this abnormality may be demonstrated in the absence of any other involvement of renal function. The severity of this renal tubular acidosis would appear to be related to the degree of hepatic disease. | [
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PMID:8767 | [Cytological, etiological and prognostic aspects of male infertility. Attempt at classification apropos of 1,303 cases]. | Study of 1303 cases of male sub-fertility led to a certain number of practical conclusions: - From a diagnostic viewpoint, the "fertility" of an individual, which is difficult to assess, depends more on the motility than the number of spermatozoa. This is most faithfully reflected in the crossed penetration test which defines the quality of penetration of a control mucus. The value of electron microscopic cytological study in the case of total asthenospermia or major monomorphous teratospermia, reflecting an irreversible constitutional abnormality of the ultrastructure of the spermatozoon, is emphasised. - From a therapeutic viewpoint, recent progress has involved the technique of surgical treatment for varicocoele as well as hormone therapy. It is essential not to neglect empirical "minor aids" indicated in the case of unexplained abnormalities (homologous artifical insemination in the case of abnormalities in the volume of the ejaculate, retard androgen therapy in the case of polyzoospermia). - From a prognostic viewpoint. The distinction must be drawn between aetiologies of good prognosis (80% of our success) responsible for transient abnormalities in spermatogenesis (infections, metabolic disturbances, varicocoele) and aetiologies with an unfavourable prognosis since they cause tubulopathies of greater or lesser severity with a lesional impairment of spermatogenesis. | [Cytological, etiological and prognostic aspects of male infertility. Attempt at classification apropos of 1,303 cases]. Study of 1303 cases of male sub-fertility led to a certain number of practical conclusions: - From a diagnostic viewpoint, the "fertility" of an individual, which is difficult to assess, depends more on the motility than the number of spermatozoa. This is most faithfully reflected in the crossed penetration test which defines the quality of penetration of a control mucus. The value of electron microscopic cytological study in the case of total asthenospermia or major monomorphous teratospermia, reflecting an irreversible constitutional abnormality of the ultrastructure of the spermatozoon, is emphasised. - From a therapeutic viewpoint, recent progress has involved the technique of surgical treatment for varicocoele as well as hormone therapy. It is essential not to neglect empirical "minor aids" indicated in the case of unexplained abnormalities (homologous artifical insemination in the case of abnormalities in the volume of the ejaculate, retard androgen therapy in the case of polyzoospermia). - From a prognostic viewpoint. The distinction must be drawn between aetiologies of good prognosis (80% of our success) responsible for transient abnormalities in spermatogenesis (infections, metabolic disturbances, varicocoele) and aetiologies with an unfavourable prognosis since they cause tubulopathies of greater or lesser severity with a lesional impairment of spermatogenesis. | [
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PMID:8774 | Management of muscle cramps in hemodialysis patients. Controlled prospective study. | In conclusion, a blind, prospective study demonstrated that HS was the most effective way of treating muscle cramps induced by hemodialysis. Hypertonic non-electrolyte solutions were less effective. The chance of a placebo effect in these patients is about 13.0%. | Management of muscle cramps in hemodialysis patients. Controlled prospective study. In conclusion, a blind, prospective study demonstrated that HS was the most effective way of treating muscle cramps induced by hemodialysis. Hypertonic non-electrolyte solutions were less effective. The chance of a placebo effect in these patients is about 13.0%. | [
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PMID:8775 | Guanosine 3':5'-cyclic monophosphate binding proteins in rat tissues. | Rat tissues were surveyed for proteins which bind cGMP. Binding activity was high in extracts of lung, cerebellum, and small intestine, but was low in those of liver, adipose tissue, and skeletal muscle. DEAE-cellulose chromatography resolved two peaks of cGMP-binding activity in most tissues. The binding protein in peak 1 was eluted in the flow-through volume and was most abundant in extracts of intestine. It had a sedimentation coefficient of 6S and was highly specific for cGMP at pH 7.0 (dissociation constant KD=0.05 muM). No cGMP-dependent histone kinase activity was found for this peak. The binding protein in peak 2 was eluted by 0.05-0.15 M NaCl and was the predominant binding substance in lung, cerebellum, and heart. It had a sedimentation coefficient of 8S and binding was also highly specific for cGMP, with a KD of 0.05 muM. This peak of binding activity was associated with cGMP-dependent protein kinase activity which could be purified approximately 200-fold by Sepharose 6B chromatography. Cyclic GMP dependency of kinase activity was observed only at low histone concentrations. The abundance of one or both the above binding proteins correlated with the known basal levels of cGMP in the tissues. | Guanosine 3':5'-cyclic monophosphate binding proteins in rat tissues. Rat tissues were surveyed for proteins which bind cGMP. Binding activity was high in extracts of lung, cerebellum, and small intestine, but was low in those of liver, adipose tissue, and skeletal muscle. DEAE-cellulose chromatography resolved two peaks of cGMP-binding activity in most tissues. The binding protein in peak 1 was eluted in the flow-through volume and was most abundant in extracts of intestine. It had a sedimentation coefficient of 6S and was highly specific for cGMP at pH 7.0 (dissociation constant KD=0.05 muM). No cGMP-dependent histone kinase activity was found for this peak. The binding protein in peak 2 was eluted by 0.05-0.15 M NaCl and was the predominant binding substance in lung, cerebellum, and heart. It had a sedimentation coefficient of 8S and binding was also highly specific for cGMP, with a KD of 0.05 muM. This peak of binding activity was associated with cGMP-dependent protein kinase activity which could be purified approximately 200-fold by Sepharose 6B chromatography. Cyclic GMP dependency of kinase activity was observed only at low histone concentrations. The abundance of one or both the above binding proteins correlated with the known basal levels of cGMP in the tissues. | [
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PMID:8776 | Subunit structure and isozymic forms of gamma-glutamyl transpeptidase. | gamma-Glutamyl transpeptidase is associated with the membranes of a number of epithelial and lymphoid cells. When the enzyme is isolated from rat kidney by a method involving detergent extraction and affinity chromatography, an aggregate of molecular weight greater than 200,000 (heavy form) is obtained. Treatment of the heavy form with bromelain yields a light form of the enzyme (molecular weight of approximately 68,000), which is separable by isoelectric focusing into 12 enzymatically active isozymes which are very similar with respect to catalytic behavior, content of amino acids, hexoses, and aminohexoses, but which differ significantly in sialic acid content. Treatment with neuraminidase converts the acidic isozymes to more basic forms. Each isozyme dissociates in sodium dodecyl sulfate into two nonidentical glycopeptides (molecular weights of 46,000 and 22,000) which can be cross-linked with dimethylsuberimidate to yield a species with an apparent molecular weight of 70,000, which indicates that the isozymes are dimers. Physical and immunological studies indicate that the heavy form of the enzyme contains the dimeric light form as well as other membrane proteins. | Subunit structure and isozymic forms of gamma-glutamyl transpeptidase. gamma-Glutamyl transpeptidase is associated with the membranes of a number of epithelial and lymphoid cells. When the enzyme is isolated from rat kidney by a method involving detergent extraction and affinity chromatography, an aggregate of molecular weight greater than 200,000 (heavy form) is obtained. Treatment of the heavy form with bromelain yields a light form of the enzyme (molecular weight of approximately 68,000), which is separable by isoelectric focusing into 12 enzymatically active isozymes which are very similar with respect to catalytic behavior, content of amino acids, hexoses, and aminohexoses, but which differ significantly in sialic acid content. Treatment with neuraminidase converts the acidic isozymes to more basic forms. Each isozyme dissociates in sodium dodecyl sulfate into two nonidentical glycopeptides (molecular weights of 46,000 and 22,000) which can be cross-linked with dimethylsuberimidate to yield a species with an apparent molecular weight of 70,000, which indicates that the isozymes are dimers. Physical and immunological studies indicate that the heavy form of the enzyme contains the dimeric light form as well as other membrane proteins. | [
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PMID:8777 | Differential degradation of messenger RNAs in mammalian cells. | Through the use of an assay that measures cellular capacity for specific enzyme synthesis, mRNA of alanine aminotransferase (EC 2.6.1.2; L-alanine:2-oxoglutarate aminotransferase) was found to be degraded with a half-life of 12-14 hr in cultured Reuber H-35 cells; mRNA of tyrosine aminotransferase (EC 2.6.1.5; L-tyrosine:2-oxoglutarate aminotransferase) has a half-life of 2 hr in the same cells. Rates of degradation of the mRNAs are the same whether new mRNA accumulation is blocked by removal of the steroid inducer or by inhibition of mRNA synthesis (actinomycin). Cycloheximide inhibits the normally rapid turnover of tyrosine aminotransferase mRNA, but agents such as puromycin and sodium fluoride, which disrupt polysome structure, do not alter the turnover rate of the tyrosine and alanine aminotransferase mRNAs. The tyrosine and alanine aminotransferase mRNAs appear to be translated at equivalent rates. The data suggest that the degradation rate of these two mRNAs is determined by the polynucleotide structure of the mRNA molecules at or near the site for ribosome binding and initiation. | Differential degradation of messenger RNAs in mammalian cells. Through the use of an assay that measures cellular capacity for specific enzyme synthesis, mRNA of alanine aminotransferase (EC 2.6.1.2; L-alanine:2-oxoglutarate aminotransferase) was found to be degraded with a half-life of 12-14 hr in cultured Reuber H-35 cells; mRNA of tyrosine aminotransferase (EC 2.6.1.5; L-tyrosine:2-oxoglutarate aminotransferase) has a half-life of 2 hr in the same cells. Rates of degradation of the mRNAs are the same whether new mRNA accumulation is blocked by removal of the steroid inducer or by inhibition of mRNA synthesis (actinomycin). Cycloheximide inhibits the normally rapid turnover of tyrosine aminotransferase mRNA, but agents such as puromycin and sodium fluoride, which disrupt polysome structure, do not alter the turnover rate of the tyrosine and alanine aminotransferase mRNAs. The tyrosine and alanine aminotransferase mRNAs appear to be translated at equivalent rates. The data suggest that the degradation rate of these two mRNAs is determined by the polynucleotide structure of the mRNA molecules at or near the site for ribosome binding and initiation. | [
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PMID:8778 | Dual role of Zn2+ as inhibitor and activator of fructose 1,6-bisphosphatase of rat liver. | At neutral pH, Zn2+ is a potent and specific inhibitor of rat liver fructose 1,6-bisphosphatase (EC 3.1.3.11; D-fructose-1,6-bisphosphate 1-phosphohydrolase). Inhibition by Zn2+ is uncompetitive with respect to the activating cations Mg2+ and Mn2+, and the kinetic data suggest that the enzyme possesses a distinct high-affinity binding site for Zn2+, with Ki of approximately 0.3 muM. At higher concentrations (about 10(-5) M) Zn2+, and to a lesser extent Co2+, function as activating cations. Binding studies show that the enzyme binds two equivalents of Zn2+ per subunit; one equivalent is partially displaced by Mg2+ and is presumably bound to the site for activating cations. A second equivalent binds to the high-affinity site, presumably identical to the inhibitory site. The results suggest that Zn2+ functions as an allosteric regulator, and that the commonly observed activation of fructose 1,6-bisphosphatase at neutral pH by EDTA, histidine, and other chelators is due to removal of endogenous Zn2+ by these agents. | Dual role of Zn2+ as inhibitor and activator of fructose 1,6-bisphosphatase of rat liver. At neutral pH, Zn2+ is a potent and specific inhibitor of rat liver fructose 1,6-bisphosphatase (EC 3.1.3.11; D-fructose-1,6-bisphosphate 1-phosphohydrolase). Inhibition by Zn2+ is uncompetitive with respect to the activating cations Mg2+ and Mn2+, and the kinetic data suggest that the enzyme possesses a distinct high-affinity binding site for Zn2+, with Ki of approximately 0.3 muM. At higher concentrations (about 10(-5) M) Zn2+, and to a lesser extent Co2+, function as activating cations. Binding studies show that the enzyme binds two equivalents of Zn2+ per subunit; one equivalent is partially displaced by Mg2+ and is presumably bound to the site for activating cations. A second equivalent binds to the high-affinity site, presumably identical to the inhibitory site. The results suggest that Zn2+ functions as an allosteric regulator, and that the commonly observed activation of fructose 1,6-bisphosphatase at neutral pH by EDTA, histidine, and other chelators is due to removal of endogenous Zn2+ by these agents. | [
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PMID:8779 | Binding of [3H]dihydroazapetine to alpha-adrenoreceptor-related proteins from rat vas deferens. | The potent alpha-adrenoreceptor blocking agent, azapetine, has been catalytically reduced with tritium gas to form [3H]dihydroazapetine. [3H]Dihydroazapetine retains significant ability to block alpha-adrenoreceptors and has been used as a ligand to study the receptor in a subcellular fraction containing membrane fragments from rat vas deferens. Specific binding of [3H]dihydroazapetine rapidly reaches equilibrium and is also reversible and saturable with a dissociation constant similar to that determined pharmacologically. The binding capacity is approximately 40 pmol/mg of protein. All alpha-adrenergic blockers tested were able to inhibit specific binding. High concentrations of alprenolol, atropine, or chlorpheniramine had no effect. In addition, all alpha-adrenergic agonists of the imidazoline class inhibit binding in low concentrations, whereas soterenol or carbamylcholine did not. There is good correlation (r=0.84) between blockade or stimulation of the receptor in intact tissues and inhibition of binding of [3H]dihydroazapetine to the subcellular fraction. These findings suggest that the fraction contains alpha-adrenoreceptor-related proteins. Alpha-adrenergic agonists structurally related to norepinephrine caused a stereoselective increase in binding in favor of the (-)-isomer, possibly reflecting an allosteric interaction at a different binding site on the receptor protein. The possibility of two different modes of binding for structurally dissimilar agonists is suggested. | Binding of [3H]dihydroazapetine to alpha-adrenoreceptor-related proteins from rat vas deferens. The potent alpha-adrenoreceptor blocking agent, azapetine, has been catalytically reduced with tritium gas to form [3H]dihydroazapetine. [3H]Dihydroazapetine retains significant ability to block alpha-adrenoreceptors and has been used as a ligand to study the receptor in a subcellular fraction containing membrane fragments from rat vas deferens. Specific binding of [3H]dihydroazapetine rapidly reaches equilibrium and is also reversible and saturable with a dissociation constant similar to that determined pharmacologically. The binding capacity is approximately 40 pmol/mg of protein. All alpha-adrenergic blockers tested were able to inhibit specific binding. High concentrations of alprenolol, atropine, or chlorpheniramine had no effect. In addition, all alpha-adrenergic agonists of the imidazoline class inhibit binding in low concentrations, whereas soterenol or carbamylcholine did not. There is good correlation (r=0.84) between blockade or stimulation of the receptor in intact tissues and inhibition of binding of [3H]dihydroazapetine to the subcellular fraction. These findings suggest that the fraction contains alpha-adrenoreceptor-related proteins. Alpha-adrenergic agonists structurally related to norepinephrine caused a stereoselective increase in binding in favor of the (-)-isomer, possibly reflecting an allosteric interaction at a different binding site on the receptor protein. The possibility of two different modes of binding for structurally dissimilar agonists is suggested. | [
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PMID:8780 | beta-endorphin is a potent analgesic agent. | beta-Endorphin, an opiate-like peptide, has potent antinociceptive properties when it is administered directly into the brain and assayed in the the tail-flick, hot-plate, and writhing tests in mice and in the wet shake test in rats. On a molar basis, beta-endorphin is 18 to 33 times more potent than morphine and its actions are blocked by the specific opiate antagonist, naloxone hydrochloride. The activity of beta-endorphin in vivo is also compared to other peptides that show opiate-like activity in assays in vitro. | beta-endorphin is a potent analgesic agent. beta-Endorphin, an opiate-like peptide, has potent antinociceptive properties when it is administered directly into the brain and assayed in the the tail-flick, hot-plate, and writhing tests in mice and in the wet shake test in rats. On a molar basis, beta-endorphin is 18 to 33 times more potent than morphine and its actions are blocked by the specific opiate antagonist, naloxone hydrochloride. The activity of beta-endorphin in vivo is also compared to other peptides that show opiate-like activity in assays in vitro. | [
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PMID:8781 | Evoked neurotransmitter release: statistical effects of nonuniformity and nonstationarity. | Recent studies of the mechanism of quantal neurotransmitter release have assumed that the number of quanta released at each stimulation is binomially distributed and have sought to estimate the binomial parameters n and p. Mathematical analysis and computer simulations show that temporal variation in the number of eligible or filled release sites and either spatial or temporal variation in the probability of release at a site can drastically bias such estimates, while the experimental histograms remain statistically indistinguishable from those predicted by the binomial law. Interpretation of the estimates n and p in terms of ultrastructural or physiological characteristics of the nerve terminal is liable to significant error if departures from the binomial assumptions are not suitably assessed. | Evoked neurotransmitter release: statistical effects of nonuniformity and nonstationarity. Recent studies of the mechanism of quantal neurotransmitter release have assumed that the number of quanta released at each stimulation is binomially distributed and have sought to estimate the binomial parameters n and p. Mathematical analysis and computer simulations show that temporal variation in the number of eligible or filled release sites and either spatial or temporal variation in the probability of release at a site can drastically bias such estimates, while the experimental histograms remain statistically indistinguishable from those predicted by the binomial law. Interpretation of the estimates n and p in terms of ultrastructural or physiological characteristics of the nerve terminal is liable to significant error if departures from the binomial assumptions are not suitably assessed. | [
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PMID:8784 | The in vitro adsorption of some antibiotics on antacids. | The adsorption of oxytetracycline hydrochloride, tetracycline hydrochloride, doxycycline hyclate, triacetyloleandomycin, chloramphenicol, ampicillin, and cloxacillin sodium was studied on various antacids namely, magnesium trisilicate, magnesium oxide, calcium carbonate, bismuth oxycarbonate, aluminium hydroxide, and kaolin. The adsorption of the various antibiotics by milk was also tested as milk is frequently used as an antacid. Charcoal was included in the present study as a model adsorbent having a large hydrophobic surface. The adsorption of the various antibiotics on the different antacids and other adsorbents in most cases obeyed the Freundlich adsorption isotherm. Magnesium trisilicate and magnesium oxide showed the highest adsorptive capacity, relative to other antacids used, for most antibiotics. Calcium carbonate and aluminium hydroxide and intermediate power while kaolin and bismuth oxycarbonate had the least adsorptive power. Charcoal exhibited a marked adsorption for all antibiotics tested. Tetracyclines were found to be more highly adsorbed than other antibiotics studied. Triacetyloleandomycin and chloramphenicol had intermediate values. Ampicillin was only adsorbed to a slight extent while cloxacillin was not adsorbed on the antacids used. The extent of adsorption was correlated to the structure of both the adsorbent and adsorbate, the pH of the adsorbent suspension, and to the polarity of the antibiotic in such pH. The reversibility of the adsorption process was studied in different media and at pH values similar to those of the gastrointestinal tract. The extent of elution was found to be inversely proportional to the adsorptive capacity of the different adsorbents. In general, 0.0143 n NaHCO3 solution was found to possess higher eluting properties than 0.01 n HCl. An exception to this pattern was observed with tetracyclines adsorbed on aluminium hydroxide where the elution with acid resulted in a higher degree of desorption. Careful in vitro and in vivo testing of drug availability is advisable prior to the concomitant administration of antibiotics with antacids or other adsorbents. | The in vitro adsorption of some antibiotics on antacids. The adsorption of oxytetracycline hydrochloride, tetracycline hydrochloride, doxycycline hyclate, triacetyloleandomycin, chloramphenicol, ampicillin, and cloxacillin sodium was studied on various antacids namely, magnesium trisilicate, magnesium oxide, calcium carbonate, bismuth oxycarbonate, aluminium hydroxide, and kaolin. The adsorption of the various antibiotics by milk was also tested as milk is frequently used as an antacid. Charcoal was included in the present study as a model adsorbent having a large hydrophobic surface. The adsorption of the various antibiotics on the different antacids and other adsorbents in most cases obeyed the Freundlich adsorption isotherm. Magnesium trisilicate and magnesium oxide showed the highest adsorptive capacity, relative to other antacids used, for most antibiotics. Calcium carbonate and aluminium hydroxide and intermediate power while kaolin and bismuth oxycarbonate had the least adsorptive power. Charcoal exhibited a marked adsorption for all antibiotics tested. Tetracyclines were found to be more highly adsorbed than other antibiotics studied. Triacetyloleandomycin and chloramphenicol had intermediate values. Ampicillin was only adsorbed to a slight extent while cloxacillin was not adsorbed on the antacids used. The extent of adsorption was correlated to the structure of both the adsorbent and adsorbate, the pH of the adsorbent suspension, and to the polarity of the antibiotic in such pH. The reversibility of the adsorption process was studied in different media and at pH values similar to those of the gastrointestinal tract. The extent of elution was found to be inversely proportional to the adsorptive capacity of the different adsorbents. In general, 0.0143 n NaHCO3 solution was found to possess higher eluting properties than 0.01 n HCl. An exception to this pattern was observed with tetracyclines adsorbed on aluminium hydroxide where the elution with acid resulted in a higher degree of desorption. Careful in vitro and in vivo testing of drug availability is advisable prior to the concomitant administration of antibiotics with antacids or other adsorbents. | [
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PMID:8793 | Kinetics and mechanism of degradation of some 5-allylbarbituric acid derivatives. Part 2: Mechanism of 5.5-diallylbarbituric acid degradation as a function of pH. | Allobarbital degradation products, produced in its aqueous solutions at different pH values, were noted by t.l.c., isolated and identified. The identification of several intermediates and the kinetic work previously done were assumed to enable one to elucidate the mechanism of the process studied. | Kinetics and mechanism of degradation of some 5-allylbarbituric acid derivatives. Part 2: Mechanism of 5.5-diallylbarbituric acid degradation as a function of pH. Allobarbital degradation products, produced in its aqueous solutions at different pH values, were noted by t.l.c., isolated and identified. The identification of several intermediates and the kinetic work previously done were assumed to enable one to elucidate the mechanism of the process studied. | [
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PMID:8794 | Migration of amphetamine and mandelic and salicylic acids in various pH buffer solutions examined via thin layer electrophoresis. | The degree of migration of optically active, racemic and non-optically active acids and bases on cellulose, silica gel and alumina thin layers is examined in various pH buffer solutions using thin layer electrophoresis. The results indicate different mobilities of the acidic and basic compounds in the various pH buffers of the experiment. | Migration of amphetamine and mandelic and salicylic acids in various pH buffer solutions examined via thin layer electrophoresis. The degree of migration of optically active, racemic and non-optically active acids and bases on cellulose, silica gel and alumina thin layers is examined in various pH buffer solutions using thin layer electrophoresis. The results indicate different mobilities of the acidic and basic compounds in the various pH buffers of the experiment. | [
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PMID:8796 | Comparisons between the antianesthetic action of dibutyryl cyclic AMP and analeptic drugs on amobarbital-induced narcosis in the rat. | The dose-related antianesthetic and antidotal property of dibutyryl cyclic AMP, devoid of toxic effects, imparts uniqueness to the nucleotide as an arousal agent. Of the analeptic drugs studied (d-amphetamine, picrotoxin, pentylenetetrazol, caffeine, theophylline, strychnine, ethamivan and doxapram), only picrotoxin demonstrated antianesthetic properties. However, picrotoxin was associated with severe toxicity at all dose levels tested. No analeptic drug is effective in reversing the central nervous system depression produced by sedative, hypnotic or tranquilizer drug overdosage. | Comparisons between the antianesthetic action of dibutyryl cyclic AMP and analeptic drugs on amobarbital-induced narcosis in the rat. The dose-related antianesthetic and antidotal property of dibutyryl cyclic AMP, devoid of toxic effects, imparts uniqueness to the nucleotide as an arousal agent. Of the analeptic drugs studied (d-amphetamine, picrotoxin, pentylenetetrazol, caffeine, theophylline, strychnine, ethamivan and doxapram), only picrotoxin demonstrated antianesthetic properties. However, picrotoxin was associated with severe toxicity at all dose levels tested. No analeptic drug is effective in reversing the central nervous system depression produced by sedative, hypnotic or tranquilizer drug overdosage. | [
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PMID:8797 | Acetylsecohemicholinium: chemical and pharmacological evaluation of an open-ring hemicholinium. | Acetylsecohemicholinium No. 3 (AcHC-3), the acetate of the open ring (seco form of hemicholinium No. 3, HC-3) hydrolyzes in vitro to the hemiacetal HC-3 at pH values above 9, a temperature-dependent conversion illustrated by ultraviolet spectral shifts from 305 to 257 mmu, and to a limited extent by certain esterases as measured by manometric analysis. An LD50 of 125 mug/kg for a neutral solution of AcHC-3 was decreased to 78.3 mug/kg (the LD50 of HC-3) upon being made basic. Prolonged treatment of mice with LD10-20 doses of AcHC-3 was associated with decreased fatty acid oxidation in the liver and resulted in infiltration of fat into hepatic cells, a reaction preventable by treatment with small doses of choline (10 mg/kg). AcHC-3 causes neuromuscular and autonomic ganglionic blockade, cholinesterase inhibition, and in vitro inhibition of acetylcholine (ACh) synthesis. These actions, although HC-3-like, appear to be due to AcHC-3 rather than HC-3 since neither cholinesterase inhibition nor hepatic ligation altered the neuromuscular blocking actions of AcHC-3. In addition to its HC-3-like properties, AcHC-3 consistently produced a transient increase in twitch height of gastrocnemius muscle before blockade and was dose-responsive in depressing blood pressure and in eliciting contractions of the isolated guinea pig ileum. AcHC-3 is both a cholinomimetic (depresses arterial blood pressure, decreases heart rate and increases ileal contractions) and a competitor of acetylcholine. That is, in most preparations tested, AcHC-3 at lower concentrations has as much intrinsic activity as ACh and at somewhat higher concentrations competitively blocks the responses to ACh. These cholinomimetic actions may be due to the presence of two ACh moieties on the AcHC-3 molecule which attach to cholinergic receptor sites. Also noted was an action of AcHC-3 that seems to be peculiar to the secohemicholiniums, namely, the potentiation of catechloamines. | Acetylsecohemicholinium: chemical and pharmacological evaluation of an open-ring hemicholinium. Acetylsecohemicholinium No. 3 (AcHC-3), the acetate of the open ring (seco form of hemicholinium No. 3, HC-3) hydrolyzes in vitro to the hemiacetal HC-3 at pH values above 9, a temperature-dependent conversion illustrated by ultraviolet spectral shifts from 305 to 257 mmu, and to a limited extent by certain esterases as measured by manometric analysis. An LD50 of 125 mug/kg for a neutral solution of AcHC-3 was decreased to 78.3 mug/kg (the LD50 of HC-3) upon being made basic. Prolonged treatment of mice with LD10-20 doses of AcHC-3 was associated with decreased fatty acid oxidation in the liver and resulted in infiltration of fat into hepatic cells, a reaction preventable by treatment with small doses of choline (10 mg/kg). AcHC-3 causes neuromuscular and autonomic ganglionic blockade, cholinesterase inhibition, and in vitro inhibition of acetylcholine (ACh) synthesis. These actions, although HC-3-like, appear to be due to AcHC-3 rather than HC-3 since neither cholinesterase inhibition nor hepatic ligation altered the neuromuscular blocking actions of AcHC-3. In addition to its HC-3-like properties, AcHC-3 consistently produced a transient increase in twitch height of gastrocnemius muscle before blockade and was dose-responsive in depressing blood pressure and in eliciting contractions of the isolated guinea pig ileum. AcHC-3 is both a cholinomimetic (depresses arterial blood pressure, decreases heart rate and increases ileal contractions) and a competitor of acetylcholine. That is, in most preparations tested, AcHC-3 at lower concentrations has as much intrinsic activity as ACh and at somewhat higher concentrations competitively blocks the responses to ACh. These cholinomimetic actions may be due to the presence of two ACh moieties on the AcHC-3 molecule which attach to cholinergic receptor sites. Also noted was an action of AcHC-3 that seems to be peculiar to the secohemicholiniums, namely, the potentiation of catechloamines. | [
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PMID:8798 | The anatomy of neurosecretory neurones in the pond snail Lymnaea stagnalis (L.). | The anatomy of three neurosecretory cell types in the central nervous system (c.n.s.) of the gastropod mollusc Lymnaea stagnalis (L.)- the Dark Green Cells, Yellow Cells and Yellow-green Cells-has been studied by using bright and dark field illumination of material stained for neurosecretion by the Alcian Blue-Alcian Yellow technique. The neuronal geometry of single and groups of neurosecretory cells of the various types has been reconstructed from serial sections, and the likely destination of most of their processes has been determined. Dark Green Cells are monopolar, occur exclusively within the central nervous system (c.n.s.), have few or no branches terminating in neuropile, and send axons to the surface of the pleuro-parietal and pleuro-cerebral connectives. The majority of Dark Green Cell axons however (80-85%), project down nerves which innervate ventral and anterior parts of the head-foot, the neck and the mantle. Dark Green Cell axons can be found in small nerves throughout these areas, and may terminate in a find plexus of axons on the surfaces of the nerves. Since previous experimental work has shown that the Dark Green Cells are involved in osmotic or ionic regulation, these results suggest that the target organ of the Dark Green Cells may be the skin. Yellow Cells occur both within and outside the c.n.s. They are usually monopolar, but can be bipolar. They have several axons which normally arise separately from a single pole of the cell body, or close to it. One or more processes leave the cell proximal to the point where separate axons arise, and may run unbranched for some distance through neuropile before terminating in fine brances and blobs of various sizes. These branches may release hormone inside the c.n.s. Yellow-green Cells are mono-, bi- or multi-polar, and like the Yellow Cells are found both within and outside the c.n.s. Some Yellow-green Cells, though not all, have projections which terminate in neuropile in fine branches and blobs. Yellow-green Cell bodies which occur in nerves can project back along the nerve into the c.n.s. The axons of Yellow Cells and Yellow-green Cells project to release sites in various ways. Some project into the connective tissue shealth of the c.n.s., which serves as a neurohaemal organ, either directly through the surface of a ganglion, or from the pleuro-cerebral or pleuro-parietal connectives. Other axons leave the c.n.s. via nerves leaving the left and right parietal and visceral ganglia; projections into the intestinal, anal, and internal right parietal nerves being most numerous. Axons which may be from either, or both Yellow Cells and Yellow-green Cells, can be found along the entire unbranched lengths of these nerves, and in subsequent branches which innervate organs lying in the anterior turn of the shell. All of these orgnas are closely associated with the lung cavity... | The anatomy of neurosecretory neurones in the pond snail Lymnaea stagnalis (L.). The anatomy of three neurosecretory cell types in the central nervous system (c.n.s.) of the gastropod mollusc Lymnaea stagnalis (L.)- the Dark Green Cells, Yellow Cells and Yellow-green Cells-has been studied by using bright and dark field illumination of material stained for neurosecretion by the Alcian Blue-Alcian Yellow technique. The neuronal geometry of single and groups of neurosecretory cells of the various types has been reconstructed from serial sections, and the likely destination of most of their processes has been determined. Dark Green Cells are monopolar, occur exclusively within the central nervous system (c.n.s.), have few or no branches terminating in neuropile, and send axons to the surface of the pleuro-parietal and pleuro-cerebral connectives. The majority of Dark Green Cell axons however (80-85%), project down nerves which innervate ventral and anterior parts of the head-foot, the neck and the mantle. Dark Green Cell axons can be found in small nerves throughout these areas, and may terminate in a find plexus of axons on the surfaces of the nerves. Since previous experimental work has shown that the Dark Green Cells are involved in osmotic or ionic regulation, these results suggest that the target organ of the Dark Green Cells may be the skin. Yellow Cells occur both within and outside the c.n.s. They are usually monopolar, but can be bipolar. They have several axons which normally arise separately from a single pole of the cell body, or close to it. One or more processes leave the cell proximal to the point where separate axons arise, and may run unbranched for some distance through neuropile before terminating in fine brances and blobs of various sizes. These branches may release hormone inside the c.n.s. Yellow-green Cells are mono-, bi- or multi-polar, and like the Yellow Cells are found both within and outside the c.n.s. Some Yellow-green Cells, though not all, have projections which terminate in neuropile in fine branches and blobs. Yellow-green Cell bodies which occur in nerves can project back along the nerve into the c.n.s. The axons of Yellow Cells and Yellow-green Cells project to release sites in various ways. Some project into the connective tissue shealth of the c.n.s., which serves as a neurohaemal organ, either directly through the surface of a ganglion, or from the pleuro-cerebral or pleuro-parietal connectives. Other axons leave the c.n.s. via nerves leaving the left and right parietal and visceral ganglia; projections into the intestinal, anal, and internal right parietal nerves being most numerous. Axons which may be from either, or both Yellow Cells and Yellow-green Cells, can be found along the entire unbranched lengths of these nerves, and in subsequent branches which innervate organs lying in the anterior turn of the shell. All of these orgnas are closely associated with the lung cavity... | [
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PMID:8799 | The rectal complex in the larvae of lepidoptera. | In the so-called "cryptonephric" condition of the excretory system in insects the distal ends of the Malpighian tubules are closely applied to the rectum and enclosed with it in a special chamber, the perinephric space, separated from the rest of the body cavity by the perinephric membrane. The term "rectal complex" refers to this association of tubules and rectum, which is found in the larvae (but not in the adults) of most Lepidoptera. In the mealworm (Coleoptera) the rectal complex has notable ability to remove water from the faeces, but this ability is not conspicuously developed in the larvae of the two species of Lepidoptera here studied: Pieris brassicae and Manduca sexta. On the other hand these larvae have notable ability to maintain salt balance under heavy dietary loading, and in this the rectal complex plays an important part. A study of salt balance in more detail has shown that more sodium can be eliminated in the faeces than enters the rectal complex from the intestine. Consideration of other possible routes of entry points strongly to the Malpighian tubules. Superimposed upon a new flow of tubule fluid out of the rectal complex there is a tidal flow, brought about by the rectal musculature and amplified by dilatations of the cryptonephric tubules, which could bring in fluid from the free tubules and afford opportunity for the uptake of salts. Evidence is presented in support of this view. This tidal flow of tubule fluid and uptake of salts could be the basis of the build-up of high osmolarity in the perinephric fluid and could contribute to the removal of water from the faeces. It could also be the basic mechanism in the mealworm, the leptophragmal mechanism being superimposed upon it. | The rectal complex in the larvae of lepidoptera. In the so-called "cryptonephric" condition of the excretory system in insects the distal ends of the Malpighian tubules are closely applied to the rectum and enclosed with it in a special chamber, the perinephric space, separated from the rest of the body cavity by the perinephric membrane. The term "rectal complex" refers to this association of tubules and rectum, which is found in the larvae (but not in the adults) of most Lepidoptera. In the mealworm (Coleoptera) the rectal complex has notable ability to remove water from the faeces, but this ability is not conspicuously developed in the larvae of the two species of Lepidoptera here studied: Pieris brassicae and Manduca sexta. On the other hand these larvae have notable ability to maintain salt balance under heavy dietary loading, and in this the rectal complex plays an important part. A study of salt balance in more detail has shown that more sodium can be eliminated in the faeces than enters the rectal complex from the intestine. Consideration of other possible routes of entry points strongly to the Malpighian tubules. Superimposed upon a new flow of tubule fluid out of the rectal complex there is a tidal flow, brought about by the rectal musculature and amplified by dilatations of the cryptonephric tubules, which could bring in fluid from the free tubules and afford opportunity for the uptake of salts. Evidence is presented in support of this view. This tidal flow of tubule fluid and uptake of salts could be the basis of the build-up of high osmolarity in the perinephric fluid and could contribute to the removal of water from the faeces. It could also be the basic mechanism in the mealworm, the leptophragmal mechanism being superimposed upon it. | [
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PMID:8800 | Genetic and anthropological studies in the human adaptability section of the International Biological Programme. | In the U.K. contribution to the H.A. (Human Adaptibility) section of I.B.P., genetic and anthropological studies have focused on three concerns. First, attempts have been made in a number of investigation to gain additional descriptive information about the genetic compostition of the world's populations. Concentrating on blood groups, blood enzymes, serum proteins and other polmorphic markers important gaps have been filled in our knowledge of the geographical paterns of human variation and of the affinities of populations wig and characterizing populations which were being studied for other purposes. For example, it was of critical concern in interpreting results to know in the investigations of climatic physiology and nutrition in Ethiopia and Israel whether the various groups studied in different environments were genetically the same or not. Finally, attention was focused in a number of investigations, especially those in New Guinea, Tristan da Cunha, Tanzania, and the Orkneys, on the factors which determine the genetic structure of populations. In these the effects of such phenomena as inbreeding, genetic drift, founder effects, migration and gene flow and the relation between genetic variety and health were examined and much attention was given to the interaction between demographic forces and genetics. | Genetic and anthropological studies in the human adaptability section of the International Biological Programme. In the U.K. contribution to the H.A. (Human Adaptibility) section of I.B.P., genetic and anthropological studies have focused on three concerns. First, attempts have been made in a number of investigation to gain additional descriptive information about the genetic compostition of the world's populations. Concentrating on blood groups, blood enzymes, serum proteins and other polmorphic markers important gaps have been filled in our knowledge of the geographical paterns of human variation and of the affinities of populations wig and characterizing populations which were being studied for other purposes. For example, it was of critical concern in interpreting results to know in the investigations of climatic physiology and nutrition in Ethiopia and Israel whether the various groups studied in different environments were genetically the same or not. Finally, attention was focused in a number of investigations, especially those in New Guinea, Tristan da Cunha, Tanzania, and the Orkneys, on the factors which determine the genetic structure of populations. In these the effects of such phenomena as inbreeding, genetic drift, founder effects, migration and gene flow and the relation between genetic variety and health were examined and much attention was given to the interaction between demographic forces and genetics. | [
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PMID:8801 | Nutrition. | Nutrition appeared somewhat late on the scene in the I.B.P. projects in the U.K., but eventually it occupied an integral part of many of the H.A. (human adaptability) investigations. The nutritional data obtained in the studies of isolated and nearisolated communities in Tristan da Cunha and in New Guinea provided information of wide nutritional significance. There were also detailed and extensive studies in Israel which, similarly to those in New Guinea, attempted to relate nutritional factors to enviroment, working conditions, and physical fitness. Some extraordinarily low energy intakes found in Ethiopians have induced much speculation on the extent which man can adequately adapt to restricted food supplies. Interesting nutritional observations, of general importance, have also arisen from results obtained on such disparate groups as Glasgow adolescents, Tanzanian and Sudanese students, children in Malawi and vegans in the U.K. | Nutrition. Nutrition appeared somewhat late on the scene in the I.B.P. projects in the U.K., but eventually it occupied an integral part of many of the H.A. (human adaptability) investigations. The nutritional data obtained in the studies of isolated and nearisolated communities in Tristan da Cunha and in New Guinea provided information of wide nutritional significance. There were also detailed and extensive studies in Israel which, similarly to those in New Guinea, attempted to relate nutritional factors to enviroment, working conditions, and physical fitness. Some extraordinarily low energy intakes found in Ethiopians have induced much speculation on the extent which man can adequately adapt to restricted food supplies. Interesting nutritional observations, of general importance, have also arisen from results obtained on such disparate groups as Glasgow adolescents, Tanzanian and Sudanese students, children in Malawi and vegans in the U.K. | [
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PMID:8802 | Work capacity, thermal responses and lung function: united kingdom studies in the L.B.P. | Results of physiological studies from some ten U.K. Human Adaptability projects are presented. U.K. investigators made major contributions in developing and adapting techniques for the assussment under field conditions of work capacity, heat tolerance and respiratory function. The various ethnic studies of work capacity revealed the special role of body size and muscularity, as well as training, in determining the observed inter- and intra-population variance. The results on samples from U.K., New Guinea, the Caribbean, Israel, West and East Africa and the Ethiopian highlands gave no indication that genetic difference were significant in determining population differences. Differences in heat tolerance reflect in general the intensity of heat exposure, especially when combined with hard physical work. Indigenous peoples in Africa and New Guinea show some modification in sweating responses which do not appear to be genetically determined but are in some way, as yet not clearly established, attributable to long continued residence in tropical climates. In renal function of some seven ethnic groups were analysed in terms of lung volume bellows function, gas exchange and responses to excercise and carbon dioxide. The relative importance of genetic and non-genetic factors was examined. | Work capacity, thermal responses and lung function: united kingdom studies in the L.B.P. Results of physiological studies from some ten U.K. Human Adaptability projects are presented. U.K. investigators made major contributions in developing and adapting techniques for the assussment under field conditions of work capacity, heat tolerance and respiratory function. The various ethnic studies of work capacity revealed the special role of body size and muscularity, as well as training, in determining the observed inter- and intra-population variance. The results on samples from U.K., New Guinea, the Caribbean, Israel, West and East Africa and the Ethiopian highlands gave no indication that genetic difference were significant in determining population differences. Differences in heat tolerance reflect in general the intensity of heat exposure, especially when combined with hard physical work. Indigenous peoples in Africa and New Guinea show some modification in sweating responses which do not appear to be genetically determined but are in some way, as yet not clearly established, attributable to long continued residence in tropical climates. In renal function of some seven ethnic groups were analysed in terms of lung volume bellows function, gas exchange and responses to excercise and carbon dioxide. The relative importance of genetic and non-genetic factors was examined. | [
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PMID:8803 | Food protein sources. | Work on food, planned by the U.M. (Use and Management) Section of the U.K. committe, was limited to sources of protein because we agreed that more problems calling for research were likely to arise in getting adequate supplies of protein than of other types of food. Deer meat can be produced on land too rough and exposed for sheep; parts of the work on their metabolism and food requirements necessitated building a mobile laboratory. The manner in which the nutritive value of maize is affected by changes in the ratios in which the component proteins are present, stimulated similar studies on barley and groundnut. There is good quality protein in coconuts and leaves but its use in human food is restricted by the presence of fibre. Methods for separating protein from fibre and other deleterious components were improved. In cooperation with scientists in India and Nigeria, the potential yield of protein-deficient foods. e.g. cassava, were 'ennobled' by growing micro-organisms on them with the addition of a cheap source of nitrogen. | Food protein sources. Work on food, planned by the U.M. (Use and Management) Section of the U.K. committe, was limited to sources of protein because we agreed that more problems calling for research were likely to arise in getting adequate supplies of protein than of other types of food. Deer meat can be produced on land too rough and exposed for sheep; parts of the work on their metabolism and food requirements necessitated building a mobile laboratory. The manner in which the nutritive value of maize is affected by changes in the ratios in which the component proteins are present, stimulated similar studies on barley and groundnut. There is good quality protein in coconuts and leaves but its use in human food is restricted by the presence of fibre. Methods for separating protein from fibre and other deleterious components were improved. In cooperation with scientists in India and Nigeria, the potential yield of protein-deficient foods. e.g. cassava, were 'ennobled' by growing micro-organisms on them with the addition of a cheap source of nitrogen. | [
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PMID:8804 | Post-embryonic development in the ventral cord of Caenorhabditis elegans. | 56 nerve cells are added to the ventral cord and associated ganglia of Caenorhabditis elegans at about the time of the first larval moult. These cells are produced by the uniform division of 13 neuroblasts followed by a defined pattern of cell deaths. Comparison with the data in the previous paper suggests that there is a relationship between the ancestry of a cell and its function. The significance of programmed cell death is discussed. | Post-embryonic development in the ventral cord of Caenorhabditis elegans. 56 nerve cells are added to the ventral cord and associated ganglia of Caenorhabditis elegans at about the time of the first larval moult. These cells are produced by the uniform division of 13 neuroblasts followed by a defined pattern of cell deaths. Comparison with the data in the previous paper suggests that there is a relationship between the ancestry of a cell and its function. The significance of programmed cell death is discussed. | [
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PMID:8805 | The pharynx of Caenorhabditis elegans. | The anatomy of the pharynx of Caenorhabditis elegans has been reconstructed from electron micrographs of serial sections. The pharynx is used for pumping food into the gut, and is composed of 34 muscle cells, 9 marginal cells, 9 epithelial cells, 5 gland cells and 20 neurones. Three regions of specialization in the cuticle lining of the pharyngeal lumen may aid in the accumulation of food particles. A basement membrane isolates the pharynx from the rest of the animal, making the pharyngeal nervous system a nearly self-contained unit which is composed primarily of five classes of motor neurones and six classes of interneurones. Three other classes have also been described, which by their morphology appear to be neurosecretory and motor, motor and interneuronal, and lastly one pair that only innervates three of the marginal cells. Some classes of neurone have free endings just under the cuticle lining the lumen of the pharynx, suggesting that these are mechano- or proprio-receptive endings. The connectivity of these neurones has been described at the level of individual synaptic regions, and after combining this information with video taped observations of the pharynx pumping, some interpretations of how these neurones function have been offered. | The pharynx of Caenorhabditis elegans. The anatomy of the pharynx of Caenorhabditis elegans has been reconstructed from electron micrographs of serial sections. The pharynx is used for pumping food into the gut, and is composed of 34 muscle cells, 9 marginal cells, 9 epithelial cells, 5 gland cells and 20 neurones. Three regions of specialization in the cuticle lining of the pharyngeal lumen may aid in the accumulation of food particles. A basement membrane isolates the pharynx from the rest of the animal, making the pharyngeal nervous system a nearly self-contained unit which is composed primarily of five classes of motor neurones and six classes of interneurones. Three other classes have also been described, which by their morphology appear to be neurosecretory and motor, motor and interneuronal, and lastly one pair that only innervates three of the marginal cells. Some classes of neurone have free endings just under the cuticle lining the lumen of the pharynx, suggesting that these are mechano- or proprio-receptive endings. The connectivity of these neurones has been described at the level of individual synaptic regions, and after combining this information with video taped observations of the pharynx pumping, some interpretations of how these neurones function have been offered. | [
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PMID:8806 | The structure of the ventral nerve cord of Caenorhabditis elegans. | The nervous system of Caenorhabditis elegans is arranged as a series of fibre bundles which run along internal hypodermal ridges. Most of the sensory integration takes place in a ring of nerve fibres which is wrapped round the pharynx in the head. The body muscles in the head are innervated by motor neurones in this nerve ring while those in the lower part of the body are innervated by a set of motor neurones in a longitudinal fibre bundle which joins the nerve ring, the ventral cord. These motor neurones can be put into five classes on the basis of their morphology and synaptic input. At any one point along the cord only one member from each class has neuromuscular junctions. Members of a given class are arranged in a regular linear sequence in the cord and have non-overlapping fields of motor synaptic activity, the transition between fields of adjacent neurones being sharp and well defined. Members of a given class form gap junctions with neighbouring members of the same class but never to motor neurones of another class. Three of the motor neurone classes receive their synaptic input from a set of interneurones coming from the nerve ring. These interneurones can in turn be grouped into four classes and each of three motor neurone classes receives its synaptic input from a unique combination of interneurone classes. The possible developmental and functional significance of these observations is discussed. | The structure of the ventral nerve cord of Caenorhabditis elegans. The nervous system of Caenorhabditis elegans is arranged as a series of fibre bundles which run along internal hypodermal ridges. Most of the sensory integration takes place in a ring of nerve fibres which is wrapped round the pharynx in the head. The body muscles in the head are innervated by motor neurones in this nerve ring while those in the lower part of the body are innervated by a set of motor neurones in a longitudinal fibre bundle which joins the nerve ring, the ventral cord. These motor neurones can be put into five classes on the basis of their morphology and synaptic input. At any one point along the cord only one member from each class has neuromuscular junctions. Members of a given class are arranged in a regular linear sequence in the cord and have non-overlapping fields of motor synaptic activity, the transition between fields of adjacent neurones being sharp and well defined. Members of a given class form gap junctions with neighbouring members of the same class but never to motor neurones of another class. Three of the motor neurone classes receive their synaptic input from a set of interneurones coming from the nerve ring. These interneurones can in turn be grouped into four classes and each of three motor neurone classes receives its synaptic input from a unique combination of interneurone classes. The possible developmental and functional significance of these observations is discussed. | [
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PMID:8807 | The ultrastructure of Gymnosphaera albida Sassaki, a marine axopodiate protozoon. | Gymnosphaera albida has been found on the sponge Sycon ciliatum in the Menai Straits, North Wales, during the months of May to December. It commonly adopts a sedentary mode of life when cultured, settling with its body in contact with the substratum and its axopodia radiating upwards and outwards all round. At times it floats freely. When sessile it can displace itself, but not by rolling. It is a voracious carnivore. The largest seen had a body size of 510 mum X 320 mum. The body of Gymnosphaera is divided into three zones: a central medulla, a cortex and a superficial reticulated pseudopodial layer. The medulla is finely vacuolated and contains an axoplast at its centre. The cortical cytoplasm contains many nuclei, Golgi bodies, polysomes, mitochondria, osmiophilic globules, lipoid spherules and vacuoles of various kinds, but no zooxanthellae. The superficial reticulated pseuopodial layer contains osmiophilic globules and occasional mitochondria. Axonemes radiate from the axoplast to the axopodia, along which osmiophilic globules are generally in motion. In between the cortex and the reticulated pseudopodial layer there is a narrow, extracytoplasmic capsular wall (Sassaki's line), consisting of a microfibrillar coagulum. The wall is a labile structure, perforating locally to allow the passage of food vacuoles or faeces and vanishing completely in certain conditions. It is evaginated to form a sleeve around the base of each axopodium. The cortex is completely penetrated by a system of clefts, the lumen of which opens here and there into the space containing the capsular wall. The clefts are distinct from the endoplasmic reticulum, cisternae of which are commonly found near the surface of the cytoplasmic tracts. Some of the cortical vacuoles contain organic refractive crystals. The crystals have the shape of crossed rodlets, each rodlet having a thermostable component ensheathing a thermolabile component. Their properties are described. The nuclei are enveloped in a thin layer of cytoplasm, connected by narrow bridges to the adjacent cytoplasmic strands. They generally contain several peripherally arranged nucleoli, each bearing a number of nucleolar organizers. Near the centre of the nucleoplasm there is usually a "central chromatin body". The vacuoles of the medulla are of two kinds, one equipped with a fibrous coat. In the vicinity of an axoneme the coat commonly connects with the microtubules and their cross-bridges. The axoplast has a central "hyalosphere" exhibiting a fibrogranular matrix. No tripartite organelle is present therein. The axoplast shell consists of the proximal ends of the axonemes, each enveloped by a fibrous sheath, the fibres coursing around adjacent axonemes, binding them together. The shell thickness is a constant fraction (1/2.5) of the axoplast diameter. The axonemes consist of bundles of parallel microtubules arranged in transverse section in a pattern of alternating rows of hexagons, the microtubules being joined together by 12.3 nm long cross-bridges... | The ultrastructure of Gymnosphaera albida Sassaki, a marine axopodiate protozoon. Gymnosphaera albida has been found on the sponge Sycon ciliatum in the Menai Straits, North Wales, during the months of May to December. It commonly adopts a sedentary mode of life when cultured, settling with its body in contact with the substratum and its axopodia radiating upwards and outwards all round. At times it floats freely. When sessile it can displace itself, but not by rolling. It is a voracious carnivore. The largest seen had a body size of 510 mum X 320 mum. The body of Gymnosphaera is divided into three zones: a central medulla, a cortex and a superficial reticulated pseudopodial layer. The medulla is finely vacuolated and contains an axoplast at its centre. The cortical cytoplasm contains many nuclei, Golgi bodies, polysomes, mitochondria, osmiophilic globules, lipoid spherules and vacuoles of various kinds, but no zooxanthellae. The superficial reticulated pseuopodial layer contains osmiophilic globules and occasional mitochondria. Axonemes radiate from the axoplast to the axopodia, along which osmiophilic globules are generally in motion. In between the cortex and the reticulated pseudopodial layer there is a narrow, extracytoplasmic capsular wall (Sassaki's line), consisting of a microfibrillar coagulum. The wall is a labile structure, perforating locally to allow the passage of food vacuoles or faeces and vanishing completely in certain conditions. It is evaginated to form a sleeve around the base of each axopodium. The cortex is completely penetrated by a system of clefts, the lumen of which opens here and there into the space containing the capsular wall. The clefts are distinct from the endoplasmic reticulum, cisternae of which are commonly found near the surface of the cytoplasmic tracts. Some of the cortical vacuoles contain organic refractive crystals. The crystals have the shape of crossed rodlets, each rodlet having a thermostable component ensheathing a thermolabile component. Their properties are described. The nuclei are enveloped in a thin layer of cytoplasm, connected by narrow bridges to the adjacent cytoplasmic strands. They generally contain several peripherally arranged nucleoli, each bearing a number of nucleolar organizers. Near the centre of the nucleoplasm there is usually a "central chromatin body". The vacuoles of the medulla are of two kinds, one equipped with a fibrous coat. In the vicinity of an axoneme the coat commonly connects with the microtubules and their cross-bridges. The axoplast has a central "hyalosphere" exhibiting a fibrogranular matrix. No tripartite organelle is present therein. The axoplast shell consists of the proximal ends of the axonemes, each enveloped by a fibrous sheath, the fibres coursing around adjacent axonemes, binding them together. The shell thickness is a constant fraction (1/2.5) of the axoplast diameter. The axonemes consist of bundles of parallel microtubules arranged in transverse section in a pattern of alternating rows of hexagons, the microtubules being joined together by 12.3 nm long cross-bridges... | [
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PMID:8808 | Peroxide induced chemiluminescence in an in vitro proline hydroxylation system. | This communication describes a hydrogen peroxide (HOOH) induced chemiluminescence (CL) in an in vitro aromatic (proline) hydroxylation system. The reactive components of the system are ascorbic (AA), ethylene diamine tetraacetic disodium salt (EDTA), ferrous sulfate, and HOOH. The CL is (1) nearly dissipated within three minutes, (2) enhanced and/or sustained by proline and polylysine to a greater degree than by alanine, (3) partially inhibited by a,a' dipyridyl, EDTA, and ethanol, (4) most dependent upon the presence of Fe2+, AA, and HOOH. The in vitro proline hydroxylation system is more effective than ground state oxygen in terms of the CL produced and the percent of hydroxyproline formed. | Peroxide induced chemiluminescence in an in vitro proline hydroxylation system. This communication describes a hydrogen peroxide (HOOH) induced chemiluminescence (CL) in an in vitro aromatic (proline) hydroxylation system. The reactive components of the system are ascorbic (AA), ethylene diamine tetraacetic disodium salt (EDTA), ferrous sulfate, and HOOH. The CL is (1) nearly dissipated within three minutes, (2) enhanced and/or sustained by proline and polylysine to a greater degree than by alanine, (3) partially inhibited by a,a' dipyridyl, EDTA, and ethanol, (4) most dependent upon the presence of Fe2+, AA, and HOOH. The in vitro proline hydroxylation system is more effective than ground state oxygen in terms of the CL produced and the percent of hydroxyproline formed. | [
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PMID:8810 | Voraciousness induced in cats by benzodiazepines. | Different benzodiazepines, when administered to fasting cats, increased both the total amount of food eaten and also the rate at which food was ingested. Moreover, when injected to foodsatiated cats, these compounds made them resume eating voraciously. Pentobarbital also stimulated food intake, but was much less potent than the benzodiazepines tested. | Voraciousness induced in cats by benzodiazepines. Different benzodiazepines, when administered to fasting cats, increased both the total amount of food eaten and also the rate at which food was ingested. Moreover, when injected to foodsatiated cats, these compounds made them resume eating voraciously. Pentobarbital also stimulated food intake, but was much less potent than the benzodiazepines tested. | [
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PMID:8811 | Drug-induced parkinsonism in the rat- a model for biochemical investigation of the parkinson-syndrome. III. The incorporation of D-glucose-14C(U) in amino acids of brain and liver from rats pretreated with reserpine or with phenothiazines. | Following treatment with reserpine or alternatively with a combination of phenothiazines (Randolektil, Majeptil) a drug-induced parkinsonoid reaction was provoked in rats. Twenty min before decapitation, 18 muCi d-glucose-14C(U) was administered intravenously. Concentration and radioactivities of glutamic acid (glu), glutamine (gln), serine (ser), and glycine (gly) were assayed in some regions of brain and in liver. Separation was performed by a combination of paper electrophoresis and chromatography or by an automatic amino acid analyzer. 1 After reserpine, the concentrations of serine and glycine were increased ten-fold while their specific activities decreased by the same factor. The interconversion serine-glycine was not affected. The concentration of glutamic acid was reduced while its specific activity remained constant. 2. After phenothiazines, the concentrations of serine and glycine in brain were also increased but their specific activities were decreased to a different degree. This indicates an additional effect on the serine-synthesis from glucose. The interconversion serine-glycine was also altered. The concentration of glutamic acid was decreased but specific activity was constant except in the thalamus region tested. 3. The influence of both treatments on amino acid turnover in liver differed from the observed impairment of brain metabolism. 4. Possible correlations between the changes in amino acid metabolism, catecholamines, and the neurologic parkinsonian symptoms are discussed. | Drug-induced parkinsonism in the rat- a model for biochemical investigation of the parkinson-syndrome. III. The incorporation of D-glucose-14C(U) in amino acids of brain and liver from rats pretreated with reserpine or with phenothiazines. Following treatment with reserpine or alternatively with a combination of phenothiazines (Randolektil, Majeptil) a drug-induced parkinsonoid reaction was provoked in rats. Twenty min before decapitation, 18 muCi d-glucose-14C(U) was administered intravenously. Concentration and radioactivities of glutamic acid (glu), glutamine (gln), serine (ser), and glycine (gly) were assayed in some regions of brain and in liver. Separation was performed by a combination of paper electrophoresis and chromatography or by an automatic amino acid analyzer. 1 After reserpine, the concentrations of serine and glycine were increased ten-fold while their specific activities decreased by the same factor. The interconversion serine-glycine was not affected. The concentration of glutamic acid was reduced while its specific activity remained constant. 2. After phenothiazines, the concentrations of serine and glycine in brain were also increased but their specific activities were decreased to a different degree. This indicates an additional effect on the serine-synthesis from glucose. The interconversion serine-glycine was also altered. The concentration of glutamic acid was decreased but specific activity was constant except in the thalamus region tested. 3. The influence of both treatments on amino acid turnover in liver differed from the observed impairment of brain metabolism. 4. Possible correlations between the changes in amino acid metabolism, catecholamines, and the neurologic parkinsonian symptoms are discussed. | [
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PMID:8812 | Generalization of morphine and lysergic acid diethylamide (LSD) stimulus properties to narcotic analgesics. | The present investigation sought to determine whether the stimulus properties of morphine and lysergic acid diethylamide (LSD) would generalize to several narcotic analgesics which vary in their subjective effects. Morphine and saline served as discriminative stimuli for one group of rats in a 2-lever discrimination task. LSD and saline were discriminative stimuli for a second group. Depression of one lever in an operant chamber resulted in reinforcement following the administration of morphine or LSD and the opposite lever was reinforced after saline. After discriminated responding was stable, stimulus generalization tests with narcotic analgesics and antagonists showed that the stimulus properties of morphine generalized to methadone and meperidine, and partially to pentazocine, all of which produce morphine-like subjective effects in humans. Morphine stimulus properties did not generalize to nalorphine or cyclazocine, which produce dissimilar subjective effects. The stimulus properties of LSD generalized partially to cyclazocine, but not to nalorphine. In humans cyclazocine and nalorphine produce a high incidence of psychotomimetic effects, but the subjective effects of cyclazocine are differentiable from those of LSD. | Generalization of morphine and lysergic acid diethylamide (LSD) stimulus properties to narcotic analgesics. The present investigation sought to determine whether the stimulus properties of morphine and lysergic acid diethylamide (LSD) would generalize to several narcotic analgesics which vary in their subjective effects. Morphine and saline served as discriminative stimuli for one group of rats in a 2-lever discrimination task. LSD and saline were discriminative stimuli for a second group. Depression of one lever in an operant chamber resulted in reinforcement following the administration of morphine or LSD and the opposite lever was reinforced after saline. After discriminated responding was stable, stimulus generalization tests with narcotic analgesics and antagonists showed that the stimulus properties of morphine generalized to methadone and meperidine, and partially to pentazocine, all of which produce morphine-like subjective effects in humans. Morphine stimulus properties did not generalize to nalorphine or cyclazocine, which produce dissimilar subjective effects. The stimulus properties of LSD generalized partially to cyclazocine, but not to nalorphine. In humans cyclazocine and nalorphine produce a high incidence of psychotomimetic effects, but the subjective effects of cyclazocine are differentiable from those of LSD. | [
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PMID:8813 | A comparison of the effects of flurazepam 30 mg and triazolam 0.5 mg on the sleep of insomniacs. | The effects of oral, bedtime triazolam 0.5 mg and flurazepam 30 mg, on the laboratory sleep of 12 insomniacs were compared in a double blind, crossover study. A 22 consecutive night schedule was used: Nts. 1--2 placebo; 3--6 first drug; 7--8 placebo; 9--14 no drugs; 15--16 placebo; 17--20 second drug; 21--22 placebo. In 6 Ss first drug was triazolam and second drug was flurazepam. In the other 6 Ss the drug order was reversed. Effects on sleep were assessed objectively by conventional EEG/EOG/EMG sleep recordings and subjectively by questionnaires administered each morning. Side or toxic effects were assessed by physical exams, clinical lab tests, and twice daily questionnaires. During their administration the two drugs were practically indistinguishable in their effects. Both significantly reduced objective and subjective measures of insomnia, such as total wake time and sleep latency. On discontinuation the drugs differentially affected sleep, e.g., on the first post flurazepam night total sleep time was significantly more than baseline whereas on first post triazolam night, total sleep time was significantly less than baseline. There were no remarkable side or toxic effects with either drug. | A comparison of the effects of flurazepam 30 mg and triazolam 0.5 mg on the sleep of insomniacs. The effects of oral, bedtime triazolam 0.5 mg and flurazepam 30 mg, on the laboratory sleep of 12 insomniacs were compared in a double blind, crossover study. A 22 consecutive night schedule was used: Nts. 1--2 placebo; 3--6 first drug; 7--8 placebo; 9--14 no drugs; 15--16 placebo; 17--20 second drug; 21--22 placebo. In 6 Ss first drug was triazolam and second drug was flurazepam. In the other 6 Ss the drug order was reversed. Effects on sleep were assessed objectively by conventional EEG/EOG/EMG sleep recordings and subjectively by questionnaires administered each morning. Side or toxic effects were assessed by physical exams, clinical lab tests, and twice daily questionnaires. During their administration the two drugs were practically indistinguishable in their effects. Both significantly reduced objective and subjective measures of insomnia, such as total wake time and sleep latency. On discontinuation the drugs differentially affected sleep, e.g., on the first post flurazepam night total sleep time was significantly more than baseline whereas on first post triazolam night, total sleep time was significantly less than baseline. There were no remarkable side or toxic effects with either drug. | [
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PMID:8814 | Clinical significance of plasma chlorpromazine levels. II. Plasma levels of the drug, some of its metabolites and prolactin in patients receiving long-term phenothiazine treatment. | Plasma levels of chlorpromazine (CPZ), 3 of its metabolites and prolactin were measured repeatedly in 18 chronic schizophrenic patients. The patients were studied while on chronic phenothiazine medication (chlorpromazine in 8, other phenothiazines in 10), during 4-6 weeks on placebo and during 6-12 weeks of CPZ treatment. The findings were compared with those obtained during acute CPZ treatment in patients who had received similar CPZ doses but no previous long-term phenothiazine medication. Plasma CPZ levels were similar in the chronic and the acute groups and so was their relation to dose. In neither group was therapeutic effect related to plasma CPZ level. In these chronic patients, in contrast to findings during acute CPZ treatment, neither prolactin level nor the appearance of parkinsonian symptoms was related to plasma drug level. In the chronic group both these effects were less pronounced during the period on CPZ which followed the placebo than were the corresponding effects during CPZ treatment in the acute group. Since plasma CPZ levels of the two groups were similar, these differences may be due to an acquired tolerance of the nervous system to some of the antidopaminergic effects of the drug. | Clinical significance of plasma chlorpromazine levels. II. Plasma levels of the drug, some of its metabolites and prolactin in patients receiving long-term phenothiazine treatment. Plasma levels of chlorpromazine (CPZ), 3 of its metabolites and prolactin were measured repeatedly in 18 chronic schizophrenic patients. The patients were studied while on chronic phenothiazine medication (chlorpromazine in 8, other phenothiazines in 10), during 4-6 weeks on placebo and during 6-12 weeks of CPZ treatment. The findings were compared with those obtained during acute CPZ treatment in patients who had received similar CPZ doses but no previous long-term phenothiazine medication. Plasma CPZ levels were similar in the chronic and the acute groups and so was their relation to dose. In neither group was therapeutic effect related to plasma CPZ level. In these chronic patients, in contrast to findings during acute CPZ treatment, neither prolactin level nor the appearance of parkinsonian symptoms was related to plasma drug level. In the chronic group both these effects were less pronounced during the period on CPZ which followed the placebo than were the corresponding effects during CPZ treatment in the acute group. Since plasma CPZ levels of the two groups were similar, these differences may be due to an acquired tolerance of the nervous system to some of the antidopaminergic effects of the drug. | [
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PMID:8815 | Characteristics of pentobarbital discrimination in the gerbil: transfer and antagonism. | Experiment 1. Gerbils were trained in a T-shaped maze to discriminate the effects produced by pentobarbital (P-barb. 15 mg/kg, i.p.) and the effects of saline. The response, a left or right turn in the maze, was thus contingent upon the prevailing training condition (P-barb. or saline). The criterion of performing 8 correct first trial choices in 10 consecutive sessions was reached within 20 training sessions. Tests with descending doses of P-barb. yielded an ED50 of 9 mg/kg. Tests with phenobarbital (40 mg/kg) or diazepam (2 and 4 mg/kg) solely maintained the drug response. P-barb. discrimination was reversed by megimide (ED50: 8.5-9.6 mg/kg) and metrazol (ED50:24.9-27.9 mg/kg). Thus megimide was approximately 3 times more effective than metrazol. Metrazol (40 and 80 mg/kg) also counteracted the phenobarbital and diazepam response. Picrotoxin (2.5 and 5 mg/kg) was less effective whereas caffeine (100 mg/kg) and piracetam (100-1000 mg/kg) did not upset P-barb. discrimination. Experiment 2. Naive gerbils had to discriminate mixtures of P-barb. (15 mg/kg) plus either 40 or 80 mg/kg of metrazol from saline already at the start of the discriminative training. The drug combinations produced discriminable effects since most gerbils reached the acquisition criterion (8/10), although more slowly than gerbils trained with P-barb, solely. Gerbils trained without a drug s-imulus (saline vs. saline) never attained the criterion during 60 consecutive sessions. In conclusion, reversal of established discrimination (Expt. 1) does not necessarily mean that the same drug combination lacks discriminable effects as demonstrated in Experiment 2. | Characteristics of pentobarbital discrimination in the gerbil: transfer and antagonism. Experiment 1. Gerbils were trained in a T-shaped maze to discriminate the effects produced by pentobarbital (P-barb. 15 mg/kg, i.p.) and the effects of saline. The response, a left or right turn in the maze, was thus contingent upon the prevailing training condition (P-barb. or saline). The criterion of performing 8 correct first trial choices in 10 consecutive sessions was reached within 20 training sessions. Tests with descending doses of P-barb. yielded an ED50 of 9 mg/kg. Tests with phenobarbital (40 mg/kg) or diazepam (2 and 4 mg/kg) solely maintained the drug response. P-barb. discrimination was reversed by megimide (ED50: 8.5-9.6 mg/kg) and metrazol (ED50:24.9-27.9 mg/kg). Thus megimide was approximately 3 times more effective than metrazol. Metrazol (40 and 80 mg/kg) also counteracted the phenobarbital and diazepam response. Picrotoxin (2.5 and 5 mg/kg) was less effective whereas caffeine (100 mg/kg) and piracetam (100-1000 mg/kg) did not upset P-barb. discrimination. Experiment 2. Naive gerbils had to discriminate mixtures of P-barb. (15 mg/kg) plus either 40 or 80 mg/kg of metrazol from saline already at the start of the discriminative training. The drug combinations produced discriminable effects since most gerbils reached the acquisition criterion (8/10), although more slowly than gerbils trained with P-barb, solely. Gerbils trained without a drug s-imulus (saline vs. saline) never attained the criterion during 60 consecutive sessions. In conclusion, reversal of established discrimination (Expt. 1) does not necessarily mean that the same drug combination lacks discriminable effects as demonstrated in Experiment 2. | [
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PMID:8818 | Structure-activity relationships among desmethyl derivatives of neuroleptics and antidepressants for substrate specificty to indolethylamine N-methyltransferase from rabbit lung. | Desmethylperazine (norperazine) and desmethylprochlorperazine (norprochlorperazine), like nor1- and nor2chlorpromazine, are excellent substrates for indolethylamine N-methyltransferase (NMT) and also inhibit the formation of dimethyltryptamine (DMT) from N-methyl-tryptamine (NMT). Nortriptyline and protriptyline, antidepressant compounds which like NMT contain a secondary amino group, also serve as substrates for INMT but lack in inhibitory effect on DMT formation. | Structure-activity relationships among desmethyl derivatives of neuroleptics and antidepressants for substrate specificty to indolethylamine N-methyltransferase from rabbit lung. Desmethylperazine (norperazine) and desmethylprochlorperazine (norprochlorperazine), like nor1- and nor2chlorpromazine, are excellent substrates for indolethylamine N-methyltransferase (NMT) and also inhibit the formation of dimethyltryptamine (DMT) from N-methyl-tryptamine (NMT). Nortriptyline and protriptyline, antidepressant compounds which like NMT contain a secondary amino group, also serve as substrates for INMT but lack in inhibitory effect on DMT formation. | [
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PMID:8820 | Effects of flurazepam (Dalmane) on anterior pituitary secretion. | Sleep stages and release patterns for growth hormone (GH), luteinizing hormone (LH) and prolactin were evaluated in two subjects during a three week period in which flurazepam 30 mg was administered nightly. Sleep stages were monitored throughout the placebo-baseline, drug and placebo-withdrawal conditions. Blood samples were obtained on nights three and four of baseline, after two and three weeks of drug administration and following extended drug withdrawal. In both subjects, flurazepam produced a marked suppression in stages 3 and 4 (slow wave) sleep which was maintained throughout the drug administration period. Following withdrawal, there was a slight increase in slow wave sleep above baseline levels. With all three hormones, no clear cut changes were observed in mean nightly output, pulse amplitude and pulse frequency from baseline to the drug and the withdrawal conditions. Thus, the decrease in slow wave sleep produced by administering flurazepam 30 mg was not accompanied by any clear cut changes in GH, LH or prolactin. | Effects of flurazepam (Dalmane) on anterior pituitary secretion. Sleep stages and release patterns for growth hormone (GH), luteinizing hormone (LH) and prolactin were evaluated in two subjects during a three week period in which flurazepam 30 mg was administered nightly. Sleep stages were monitored throughout the placebo-baseline, drug and placebo-withdrawal conditions. Blood samples were obtained on nights three and four of baseline, after two and three weeks of drug administration and following extended drug withdrawal. In both subjects, flurazepam produced a marked suppression in stages 3 and 4 (slow wave) sleep which was maintained throughout the drug administration period. Following withdrawal, there was a slight increase in slow wave sleep above baseline levels. With all three hormones, no clear cut changes were observed in mean nightly output, pulse amplitude and pulse frequency from baseline to the drug and the withdrawal conditions. Thus, the decrease in slow wave sleep produced by administering flurazepam 30 mg was not accompanied by any clear cut changes in GH, LH or prolactin. | [
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PMID:8821 | Biochemical localization of gamma-glutamyl transpeptidase within cellular elements of the rat cerebral cortex. | The presence of the enzyme gamma-glutamyl transpeptidase was established in cellular elements of the rat cerebral cortex. Lowest enzyme activity was found in the total cerebral homogenate while approximately four-fold increased enzymatic activities were evident in capillary-enriched, glial-enriched and purified neuronal fractions. | Biochemical localization of gamma-glutamyl transpeptidase within cellular elements of the rat cerebral cortex. The presence of the enzyme gamma-glutamyl transpeptidase was established in cellular elements of the rat cerebral cortex. Lowest enzyme activity was found in the total cerebral homogenate while approximately four-fold increased enzymatic activities were evident in capillary-enriched, glial-enriched and purified neuronal fractions. | [
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