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PMID:10587 | Unwanted effects of long-term medication in schizophrenia and depression. | Medicine is an experimental science which proceeds by trial and error, and with pharmacotherapy doctors must continually review the drugs at their disposal for both effectiveness and adverse effects. These adverse effects must be assessed not only in relation to the therapeutic effect, but also, of course, in relation to the severity of the patient's illness and the likely prognosis in the absence of treatment. In this review I will select one or two side effects in each of the major group of drugs for consideration. | Unwanted effects of long-term medication in schizophrenia and depression. Medicine is an experimental science which proceeds by trial and error, and with pharmacotherapy doctors must continually review the drugs at their disposal for both effectiveness and adverse effects. These adverse effects must be assessed not only in relation to the therapeutic effect, but also, of course, in relation to the severity of the patient's illness and the likely prognosis in the absence of treatment. In this review I will select one or two side effects in each of the major group of drugs for consideration. | [
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PMID:10589 | Malaria of the orang-utan (Pongo pygmaeus) in Borneo. | The primary objective of this project was to study the life cycle and ecology of Plasmodium pitheci, a malaria parasite of the orang-utan. The field work was based on the orang-utan rehabilitation centre in the Sepilok Forest Reserve of eastern Sabah. Two visits were made to Sepilok, the first in February and March, 1972, and the second (by W.P.) in January 1974. On the first visit two species of "surrogate host" were taken to Sabah, i.e. chimpanzees and Aotus monkeys for experimental work. The arboreal habitat of the orang-utan in the dipterocarp forests of eastern Sabah is described. In the Sepilok Forest Reserve dwell gibbons and leaf-monkeys, in addition to a small population of semi-domesticated and wild, free-ranging orang-utans of various ages. Although numerous species of anopheline mosquitoes have been collected in eastern Sabah, longitudinal studies are not available. Anopheles balabacensis was caught both attracted to orang-utans and to man at Sepilok. This species which is the main vector of human malaria in the north of Borneo, is suspected also of transmitting orang-utan malaria in this part of Sabah. Repeated blood examinations have been made on a number of orang-utans in the centre since 1966 and a high prevalence of infection was recorded with Plasmodium pitheci. In 1966 10 out of 19 animals had demonstrable parasitaemia. Detailed case histories are presented to show the course of parasitaemia in several orang-utans. Infections of P. pitheci were found to run a very chronic course. During the 1972 expedition a second, previously undescribed malaria parasite of the orang-utan was discovered, and was named P. silvaticum. The new parasite was successfully transmitted both by blood inoculation and, later, by sporozoite inoculation, into splenectomized chimpanzees. Although both species of malaria parasite may cause transitory signs of illness, orang-utans in general appear to be little discomforted by the infection. The animals do however suffer from other infectious diseases such as amoebic and balantidial dysentery, and melioidosis is a serious natural hazard which may have accounted for several deaths of wild orang-utans. An unidentified, intraerythrocytic structure that appeared in the blood of one chimpanzee, which had been inoculated with blood from an orang-utan, may have contributed to its death. Detailed descriptions and illustrations of P. pitheci and P. silvaticum are given. All stages of the life cycle of P. silvaticum are known (the tissue stages having been described in the liver of a "surrogate host", the chimpanzee) but only the blood and sporogonic stages of P. pitheci have been seen. This species was not infective to a chimpanzee, although there is an earlier report of a transient infection in this host by other workers. In the blood both parasites showed a tertian periodicity. From the appearance of the tissue schizonts on the seventh day it was estimated that the complete pre-erythrocytic cycle of P. silvaticum in the chimpanzee would occupy 8 days. P... | Malaria of the orang-utan (Pongo pygmaeus) in Borneo. The primary objective of this project was to study the life cycle and ecology of Plasmodium pitheci, a malaria parasite of the orang-utan. The field work was based on the orang-utan rehabilitation centre in the Sepilok Forest Reserve of eastern Sabah. Two visits were made to Sepilok, the first in February and March, 1972, and the second (by W.P.) in January 1974. On the first visit two species of "surrogate host" were taken to Sabah, i.e. chimpanzees and Aotus monkeys for experimental work. The arboreal habitat of the orang-utan in the dipterocarp forests of eastern Sabah is described. In the Sepilok Forest Reserve dwell gibbons and leaf-monkeys, in addition to a small population of semi-domesticated and wild, free-ranging orang-utans of various ages. Although numerous species of anopheline mosquitoes have been collected in eastern Sabah, longitudinal studies are not available. Anopheles balabacensis was caught both attracted to orang-utans and to man at Sepilok. This species which is the main vector of human malaria in the north of Borneo, is suspected also of transmitting orang-utan malaria in this part of Sabah. Repeated blood examinations have been made on a number of orang-utans in the centre since 1966 and a high prevalence of infection was recorded with Plasmodium pitheci. In 1966 10 out of 19 animals had demonstrable parasitaemia. Detailed case histories are presented to show the course of parasitaemia in several orang-utans. Infections of P. pitheci were found to run a very chronic course. During the 1972 expedition a second, previously undescribed malaria parasite of the orang-utan was discovered, and was named P. silvaticum. The new parasite was successfully transmitted both by blood inoculation and, later, by sporozoite inoculation, into splenectomized chimpanzees. Although both species of malaria parasite may cause transitory signs of illness, orang-utans in general appear to be little discomforted by the infection. The animals do however suffer from other infectious diseases such as amoebic and balantidial dysentery, and melioidosis is a serious natural hazard which may have accounted for several deaths of wild orang-utans. An unidentified, intraerythrocytic structure that appeared in the blood of one chimpanzee, which had been inoculated with blood from an orang-utan, may have contributed to its death. Detailed descriptions and illustrations of P. pitheci and P. silvaticum are given. All stages of the life cycle of P. silvaticum are known (the tissue stages having been described in the liver of a "surrogate host", the chimpanzee) but only the blood and sporogonic stages of P. pitheci have been seen. This species was not infective to a chimpanzee, although there is an earlier report of a transient infection in this host by other workers. In the blood both parasites showed a tertian periodicity. From the appearance of the tissue schizonts on the seventh day it was estimated that the complete pre-erythrocytic cycle of P. silvaticum in the chimpanzee would occupy 8 days. P... | [
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PMID:10591 | Different susceptibilities to intracellular proteases of hemoglobin and hemoglobin-haptoglobin complex. | The susceptibilities of hemoglobin and hemoglobin-haptoglobin complex to intracellular proteases differ significantly. Hemoglobin and hemoglobin-haptoglobin complex are degested in the regions of pH 5.5-2.5 and 4.0-2.5 respectively, having pH optima at pH 4.0 and 3.0 respectively, by intracellular proteases from rat and mouse liver or spleen. The difference in proteolytic susceptibility is found to be due to the different stabilities to acid among hemoglobin derivatives as evidenced by the measurements of their helical contents in acidic pH. | Different susceptibilities to intracellular proteases of hemoglobin and hemoglobin-haptoglobin complex. The susceptibilities of hemoglobin and hemoglobin-haptoglobin complex to intracellular proteases differ significantly. Hemoglobin and hemoglobin-haptoglobin complex are degested in the regions of pH 5.5-2.5 and 4.0-2.5 respectively, having pH optima at pH 4.0 and 3.0 respectively, by intracellular proteases from rat and mouse liver or spleen. The difference in proteolytic susceptibility is found to be due to the different stabilities to acid among hemoglobin derivatives as evidenced by the measurements of their helical contents in acidic pH. | [
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PMID:10592 | Mechanoelectrical transduction in hyaluronic acid salt solution is an entropy-driven process. | An electrical potential develops between the ends of a column of hyaluronic salt solution displaced from a resting position by gentle pressure. A previous study demonstrated that such displacement changes the optical rotary dispersion properties of the salt, either increasing the rotation in the direction already shown by the salt before displacement or changing and increasing the rotation in the opposite direction, depending on the direction of the displacement. The present investigation demonstrates that the loss of bound water component across a membrane separating the solution and water is corelated with the extent of the column displacement. In addition, a return of the column to the position before displacement is correlated with a return of the water component across the membrane-but not at the same rate as the exodus. The data seem consistent with the hypothesis that the hyaluronic acid salt, when strained, adopts a less entropic configuration, releasing bound water and thus increasing the entropy of water component. This change in the distribution of entropy is reversible; i.e., Eddington's "time's arrow" is reversible with respect to the water component of the solution. | Mechanoelectrical transduction in hyaluronic acid salt solution is an entropy-driven process. An electrical potential develops between the ends of a column of hyaluronic salt solution displaced from a resting position by gentle pressure. A previous study demonstrated that such displacement changes the optical rotary dispersion properties of the salt, either increasing the rotation in the direction already shown by the salt before displacement or changing and increasing the rotation in the opposite direction, depending on the direction of the displacement. The present investigation demonstrates that the loss of bound water component across a membrane separating the solution and water is corelated with the extent of the column displacement. In addition, a return of the column to the position before displacement is correlated with a return of the water component across the membrane-but not at the same rate as the exodus. The data seem consistent with the hypothesis that the hyaluronic acid salt, when strained, adopts a less entropic configuration, releasing bound water and thus increasing the entropy of water component. This change in the distribution of entropy is reversible; i.e., Eddington's "time's arrow" is reversible with respect to the water component of the solution. | [
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PMID:10599 | Necroqizing enterocolitis with pneumatosis intestinalis in systemic lupus erythematosus and polyarteritis. | Pneumatosis intestinalis was encountered in association with fatal necrotizing enterocolitis in systemic lupus erythematosus (SLE) and polyarteritis nodosa. The radiologic identification of mottled, bubbly, and linear collections of intramural intestinal gas distinguish this ominous complication from benign pneumatosis cystoides intestinalis. In the setting of intestinal vasculitis due to SLE or polyarteritis nodosa, these characteristic radiologic features indicate necrotizing enterocolitis. Since corticosteroids may mask clinical progression of the intestinal lesion, radiologic evaluation is essential in the overall management of the patient with intestinal vasculitis. | Necroqizing enterocolitis with pneumatosis intestinalis in systemic lupus erythematosus and polyarteritis. Pneumatosis intestinalis was encountered in association with fatal necrotizing enterocolitis in systemic lupus erythematosus (SLE) and polyarteritis nodosa. The radiologic identification of mottled, bubbly, and linear collections of intramural intestinal gas distinguish this ominous complication from benign pneumatosis cystoides intestinalis. In the setting of intestinal vasculitis due to SLE or polyarteritis nodosa, these characteristic radiologic features indicate necrotizing enterocolitis. Since corticosteroids may mask clinical progression of the intestinal lesion, radiologic evaluation is essential in the overall management of the patient with intestinal vasculitis. | [
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PMID:10602 | Biochemical properties of the prostaglandin/thromboxane synthetase of human blood platelets and comparison with the synthetase of bovine seminal vesicles. | The enzyme system which synthesizes prostaglandins and thromboxanes in extracts of washed human platelets has been characterized with respect to kinetic parameters, pH and cofactor dependence, and inhibitor potencies. Arachidonate and dihomo-gamma-linolenate were shown to be mutually competitive substrates, thus providing biochemical support for the assumption that both substrates are metabolized by the same cyclooxygenase, although they are ultimately metabolized to different patterns of products. Products of the synthetase of human leucocytes qualitatively resemble those obtained with human platelets. The prostaglandin synthetase of bovine seminal vesicles was studied under similar conditions, and kinetic parameters and inhibitor potencies were compared with those of platelet extracts. | Biochemical properties of the prostaglandin/thromboxane synthetase of human blood platelets and comparison with the synthetase of bovine seminal vesicles. The enzyme system which synthesizes prostaglandins and thromboxanes in extracts of washed human platelets has been characterized with respect to kinetic parameters, pH and cofactor dependence, and inhibitor potencies. Arachidonate and dihomo-gamma-linolenate were shown to be mutually competitive substrates, thus providing biochemical support for the assumption that both substrates are metabolized by the same cyclooxygenase, although they are ultimately metabolized to different patterns of products. Products of the synthetase of human leucocytes qualitatively resemble those obtained with human platelets. The prostaglandin synthetase of bovine seminal vesicles was studied under similar conditions, and kinetic parameters and inhibitor potencies were compared with those of platelet extracts. | [
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PMID:10603 | Tardive dyskinesia and depressive illness. | Tardive dyskinesia has been regarded as a long-term complication of neuroleptic administration to patients with the diagnosis of schizophrenia. However, nine of the first fourteen patients evaluated for an investigation of tardive dyskinesia met diagnostic criteria for depression. Neuroleptics produce blockade of post-synaptic dopaminergic receptors. Tardive dyskinesia occurs when neuroleptics are discontinued, and is regarded as a manifestation of super-sensitive post-synaptic dopaminergic receptors. Tardive dyskinesia occurs when neuroleptics are discontinued, and is regarded as a manifestation of super-sensitive post-synaptic dopaminergic receptors. Chronically decreased neurotransmission in the synapse of a patient with depression may contribute to the development of a super-sensitive receptor and could explain the high proportion of patients with depression seen in this sample of patients with tardive dyskinesia. | Tardive dyskinesia and depressive illness. Tardive dyskinesia has been regarded as a long-term complication of neuroleptic administration to patients with the diagnosis of schizophrenia. However, nine of the first fourteen patients evaluated for an investigation of tardive dyskinesia met diagnostic criteria for depression. Neuroleptics produce blockade of post-synaptic dopaminergic receptors. Tardive dyskinesia occurs when neuroleptics are discontinued, and is regarded as a manifestation of super-sensitive post-synaptic dopaminergic receptors. Tardive dyskinesia occurs when neuroleptics are discontinued, and is regarded as a manifestation of super-sensitive post-synaptic dopaminergic receptors. Chronically decreased neurotransmission in the synapse of a patient with depression may contribute to the development of a super-sensitive receptor and could explain the high proportion of patients with depression seen in this sample of patients with tardive dyskinesia. | [
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PMID:10604 | Weight-bearing deficiency of the 1st metatarsal ray. | The authors have analysed a special disturbance of the statics and dynamics of the forefoot - deficient weight-bearing on the first metatarsal ray whilst walking. From the clinical point of view, the condition resulted in the development of a dorsal bunion and metatarsalgia. Forty-nine cases were treated and seven causative factors were discovered: Club foot, Paralysis, Congenital deformity, Fracture-dislocation of Lisfranc's joint, Sequelae of surgery for hallux valgus, Sequelae of subtaler arthrodesis, "Functional" abnormality. | Weight-bearing deficiency of the 1st metatarsal ray. The authors have analysed a special disturbance of the statics and dynamics of the forefoot - deficient weight-bearing on the first metatarsal ray whilst walking. From the clinical point of view, the condition resulted in the development of a dorsal bunion and metatarsalgia. Forty-nine cases were treated and seven causative factors were discovered: Club foot, Paralysis, Congenital deformity, Fracture-dislocation of Lisfranc's joint, Sequelae of surgery for hallux valgus, Sequelae of subtaler arthrodesis, "Functional" abnormality. | [
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PMID:10605 | Measurement of glycolytic rates in cell suspensions using a recording pH meter. | A method for measuring continuously glycolytic rates in cell suspensions, using a recording pH meter, is described. Under the described conditions the method is very exact, sensitive and reproducible. The method can be applied to different cells and different conditions of assay calibrating in each case the pH range, cell concentration range and the ratio of delta protons to delta lactic acid. | Measurement of glycolytic rates in cell suspensions using a recording pH meter. A method for measuring continuously glycolytic rates in cell suspensions, using a recording pH meter, is described. Under the described conditions the method is very exact, sensitive and reproducible. The method can be applied to different cells and different conditions of assay calibrating in each case the pH range, cell concentration range and the ratio of delta protons to delta lactic acid. | [
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] |
PMID:10606 | Characterization and induction of aryl hydrocarbon (benzo(a)pyrene) hydroxylase in rabbit bone marrow. | Benzo(a)pyrene hydroxylase activity was found in the bone marrow of control and 3MC-induced New Zealand white rabbits. This activity was localized in the microsomal fraction, was NADPH dependent and CO sensitive. The reaction was inhibited by 7,8-benzoflavone indicating that it was mediated by the 3MC-inducible form of cytochrome P-450. BP hydroxylase activity in rabbit bone marrow was located primarily in white cells, and was considerably higher than that previously reported for cultured human lymphocytes and monocytes. A possible role for the bone marrow mixed-function oxygenase in the production of hemopoietic toxicity is considered. | Characterization and induction of aryl hydrocarbon (benzo(a)pyrene) hydroxylase in rabbit bone marrow. Benzo(a)pyrene hydroxylase activity was found in the bone marrow of control and 3MC-induced New Zealand white rabbits. This activity was localized in the microsomal fraction, was NADPH dependent and CO sensitive. The reaction was inhibited by 7,8-benzoflavone indicating that it was mediated by the 3MC-inducible form of cytochrome P-450. BP hydroxylase activity in rabbit bone marrow was located primarily in white cells, and was considerably higher than that previously reported for cultured human lymphocytes and monocytes. A possible role for the bone marrow mixed-function oxygenase in the production of hemopoietic toxicity is considered. | [
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PMID:10607 | NADPH dependent lipid peroxidation of calcium bound microsomes. | Rat liver microsomes prepared by a calcium aggregation method have been found capable of readily undergoing NADPH induced lipid peroxidation. Malonic dialdehyde production of calcium bound microsomes is equivalent to that attained by microsomes prepared by ultracentrifugation. In addition these calcium bound microsomes can be quickly removed from suspension by means of ultrafiltration. | NADPH dependent lipid peroxidation of calcium bound microsomes. Rat liver microsomes prepared by a calcium aggregation method have been found capable of readily undergoing NADPH induced lipid peroxidation. Malonic dialdehyde production of calcium bound microsomes is equivalent to that attained by microsomes prepared by ultracentrifugation. In addition these calcium bound microsomes can be quickly removed from suspension by means of ultrafiltration. | [
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PMID:10608 | Molecular complexes of cocaine, its active metabolites and some other stimulants with thiamine. | Cocaine, its pharmacologically active metabolites, norcocaine benzoylnorecgonine, benzoylecgonine and other central nervous system stimulants e.g. dextrococaine, nicotine, caffeine and p-hydroxy norephedrine formed molecular complexes with thiamine. The possible implications of such an interaction are discussed. | Molecular complexes of cocaine, its active metabolites and some other stimulants with thiamine. Cocaine, its pharmacologically active metabolites, norcocaine benzoylnorecgonine, benzoylecgonine and other central nervous system stimulants e.g. dextrococaine, nicotine, caffeine and p-hydroxy norephedrine formed molecular complexes with thiamine. The possible implications of such an interaction are discussed. | [
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PMID:10609 | [Immune status of indefinitely surviving rat renal allograft recipients after short course of ALS-treatment Detection of a serum blocking factor by allorosette formation inhibition test (author's transl)]. | 53 LBNF1 kidneys were grafted into L-rats. 24 untreated recipients served as control and survived 16.1 +/- 1.7 days. 14 recipients were treated with 4 ml alloantiserum (ADS) each, and the other 15 animals with 4 ml ALS each. 9 and 10 of these 14 and 15 animals survived for more than 4 months. We performed GvH-reaction with spleen cells of these 19 animals. It showed normal cellular immune response. After splenectomy first donor specific skin was transplanted, 18 days later second skin of same origin (LBNF1) and 18' days after third party skin (LBufF1). The first grafts survived 13.1 +/- 1.9 days in the recipients of ADS treatment and 12.2 +/- 1.2 days in the recipients of ALS. Second skin grafts were rejected delayed in the former recipients as the first grafts, in the later more accelerated than the first grafts. The third grafts survived as the controls. Before and after skin grafting we could not detect lymphocytotoxin and hemagglutinin. The sera of animals with ADS therapy inhibited the spontaneous allorosette formation to 46.0 +/- 4.4% and of ALS therapy 37.7 +/- 9.2%. Our results suggest that after ALS treatment blocking antibodies were produced in the recipients and they cause the enhancement of kidney allograft. | [Immune status of indefinitely surviving rat renal allograft recipients after short course of ALS-treatment Detection of a serum blocking factor by allorosette formation inhibition test (author's transl)]. 53 LBNF1 kidneys were grafted into L-rats. 24 untreated recipients served as control and survived 16.1 +/- 1.7 days. 14 recipients were treated with 4 ml alloantiserum (ADS) each, and the other 15 animals with 4 ml ALS each. 9 and 10 of these 14 and 15 animals survived for more than 4 months. We performed GvH-reaction with spleen cells of these 19 animals. It showed normal cellular immune response. After splenectomy first donor specific skin was transplanted, 18 days later second skin of same origin (LBNF1) and 18' days after third party skin (LBufF1). The first grafts survived 13.1 +/- 1.9 days in the recipients of ADS treatment and 12.2 +/- 1.2 days in the recipients of ALS. Second skin grafts were rejected delayed in the former recipients as the first grafts, in the later more accelerated than the first grafts. The third grafts survived as the controls. Before and after skin grafting we could not detect lymphocytotoxin and hemagglutinin. The sera of animals with ADS therapy inhibited the spontaneous allorosette formation to 46.0 +/- 4.4% and of ALS therapy 37.7 +/- 9.2%. Our results suggest that after ALS treatment blocking antibodies were produced in the recipients and they cause the enhancement of kidney allograft. | [
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PMID:10610 | [The Göttinger minipig as a laboratory animal (author's transl)]. | Blood pictures, serumelectrolytes, acid-base- and bloodgas-values of the arterial blood were determined from two juvenile and one adulte collectives of minipigs (Gottingen strain), which were kept under SPF-conditions. The results were compared with the corresponding values of human blood and should be regarded as base- or orienting values for further investigations. | [The Göttinger minipig as a laboratory animal (author's transl)]. Blood pictures, serumelectrolytes, acid-base- and bloodgas-values of the arterial blood were determined from two juvenile and one adulte collectives of minipigs (Gottingen strain), which were kept under SPF-conditions. The results were compared with the corresponding values of human blood and should be regarded as base- or orienting values for further investigations. | [
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PMID:10611 | [Studies on the pH-dependence, inhibition and reactivation of angiotension II-amide splitting enzymes in human erythrocytes (author's transl)]. | Aminopeptidase activity of three fractions of human erythrocytes (membranes free of hemoglobin; hemolysate free of membranes; enzyme protein fraction made free of hemoglobin by DEAE-cellulose) was measured by a NADH dependent optical test using asparaginyl1-angiotension II-amide as substrate. 1. From the enzyme protein fraction 6 subfractions were obtained by (NH4)2SO4 precipitation. By measuring enzyme kinetics at three different pH-values (pH 5,0; 7,0; 8,0) with and without addition of the effectors Na2EDTA and Ca++ the existence of 6 different enzymes could be demonstrated. 2. The aminopeptidase activity of the hemolysate made free of membranes could be inhibited by diisopropylfluorphosphate and p-chloromercuribenzoate at three different pH-values (pH 5,0; 6,5; 7,0; 8,0 and 6,5; 7,0; 8,0 respectively). 3. A reduction of enzymatic activity of 20% was found after incubation at 37degreesC for two hours. | [Studies on the pH-dependence, inhibition and reactivation of angiotension II-amide splitting enzymes in human erythrocytes (author's transl)]. Aminopeptidase activity of three fractions of human erythrocytes (membranes free of hemoglobin; hemolysate free of membranes; enzyme protein fraction made free of hemoglobin by DEAE-cellulose) was measured by a NADH dependent optical test using asparaginyl1-angiotension II-amide as substrate. 1. From the enzyme protein fraction 6 subfractions were obtained by (NH4)2SO4 precipitation. By measuring enzyme kinetics at three different pH-values (pH 5,0; 7,0; 8,0) with and without addition of the effectors Na2EDTA and Ca++ the existence of 6 different enzymes could be demonstrated. 2. The aminopeptidase activity of the hemolysate made free of membranes could be inhibited by diisopropylfluorphosphate and p-chloromercuribenzoate at three different pH-values (pH 5,0; 6,5; 7,0; 8,0 and 6,5; 7,0; 8,0 respectively). 3. A reduction of enzymatic activity of 20% was found after incubation at 37degreesC for two hours. | [
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PMID:10613 | Carbonic anhydrase inhibitor in trout plasma. | A manometric assay has been constructed such that carbonic anhydrase dehydration activity can be determined utilizing intact erythrocytes. It was found that unwashed whole trout blood lacks any dehydration activity quite in contrast to whole rat blood. Removal of the plasma and replacement with physiological saline results in pronounced dehydration activity with inhibition restored by replacing the saline with the original plasma. An inhibitor residing in the plasma (probably a protein but not yet fully characterized) is capable of limiting in vivo dehydration activity. The inhibitor could work at the level of the enzyme per se or by inhibiting erythrocytic HCO3 influx, or both. The lack of erythrocytic dehydration activity presumably would alter CO2 excretion patterns; possible implications are discussed. | Carbonic anhydrase inhibitor in trout plasma. A manometric assay has been constructed such that carbonic anhydrase dehydration activity can be determined utilizing intact erythrocytes. It was found that unwashed whole trout blood lacks any dehydration activity quite in contrast to whole rat blood. Removal of the plasma and replacement with physiological saline results in pronounced dehydration activity with inhibition restored by replacing the saline with the original plasma. An inhibitor residing in the plasma (probably a protein but not yet fully characterized) is capable of limiting in vivo dehydration activity. The inhibitor could work at the level of the enzyme per se or by inhibiting erythrocytic HCO3 influx, or both. The lack of erythrocytic dehydration activity presumably would alter CO2 excretion patterns; possible implications are discussed. | [
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PMID:10614 | Intracellular pH in cold-blooded vertebrates as a function of body temperature. | Intracellular pH (pHi) was measured in vivo in tissue of frogs (Rana catesbeiana) and turtles (Pseudemys scripta) using the DMO technique. Animals were permitted 3-8 days to come to a new steady-state body temperature (Tb) which ranged 5-32 degrees C. Least squares regression equation for pHi data are: frog blood, 8.184-0.0206 Tb; frog striated muscle, 7.275-0.0152 Tb; turtle blood, 8.092-0.0207Tb; turtle muscle, 7.421-0.0186 Tb; turtle heart, 7.452-0.0122 Tb; turtle liver, 7.753-0.0233 Tb; turtle esophageal smooth muscle, 7.513-0.0141 Tb. Only turtle cardiac muscle deltapHi/deltaT was significantly different from deltapH/deltaT of blood. Results have been interpreted in terms of protein charge state alterations; in the physiological pH range, histidine residues of proteins are the principal dissociable groups (HPr+ = H+ + Pr) affected by pHi and Tb changes. Constancy of protein charge state can be assessed by monitoring alpha imidazole, alphaIM = Pr/(HPr+ + Pr). A uniform pKIM of 6.85 (20degreesC) and a deltaHO of 7 kcal/mol are assumed in calculating alphaIM. Intracellular alphaIM is preserved in the tissues studied as body temperature changes. These results indicate that ectotherm acid-base balance, alphastat control, regulates not only extracellular blood proteins, but also intracellular compartment proteins in such a way as to preserve functions dependent upon protein net charge states. | Intracellular pH in cold-blooded vertebrates as a function of body temperature. Intracellular pH (pHi) was measured in vivo in tissue of frogs (Rana catesbeiana) and turtles (Pseudemys scripta) using the DMO technique. Animals were permitted 3-8 days to come to a new steady-state body temperature (Tb) which ranged 5-32 degrees C. Least squares regression equation for pHi data are: frog blood, 8.184-0.0206 Tb; frog striated muscle, 7.275-0.0152 Tb; turtle blood, 8.092-0.0207Tb; turtle muscle, 7.421-0.0186 Tb; turtle heart, 7.452-0.0122 Tb; turtle liver, 7.753-0.0233 Tb; turtle esophageal smooth muscle, 7.513-0.0141 Tb. Only turtle cardiac muscle deltapHi/deltaT was significantly different from deltapH/deltaT of blood. Results have been interpreted in terms of protein charge state alterations; in the physiological pH range, histidine residues of proteins are the principal dissociable groups (HPr+ = H+ + Pr) affected by pHi and Tb changes. Constancy of protein charge state can be assessed by monitoring alpha imidazole, alphaIM = Pr/(HPr+ + Pr). A uniform pKIM of 6.85 (20degreesC) and a deltaHO of 7 kcal/mol are assumed in calculating alphaIM. Intracellular alphaIM is preserved in the tissues studied as body temperature changes. These results indicate that ectotherm acid-base balance, alphastat control, regulates not only extracellular blood proteins, but also intracellular compartment proteins in such a way as to preserve functions dependent upon protein net charge states. | [
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PMID:10615 | Model studies of intracellular acid-base temperature responses in ectotherms. | Measurements of intracellular pH (pHi) in air-breathing ectotherms have only been made in the steady state; these pHi indicate that protein charge state, measured as alpha imidazole (alphaIM), the fractional dissociation of protein histidine imidazole groups, is preserved when ectotherm tissues change temperature in vivo, with related changes in pHi and PCO2. In partial answer to the question of how such tissues are able to avoid disrupting transients to functions sensitive to protein charge states, model studies were carried out to assess the passive intracellular buffer system response to a combined change in body temperature and CO2 partial pressure as occurs in vivo in these species. The cell compartment was modeled as a closed volume of ternary buffer solution, containing protein imidazole (50 mM/1); phosphate (15 mM/1) and CO2-bicarbonate buffer components, permeable only to CO2 and permitted no change in buffer base. Excursions from a steady-state non-equilibrium pHi were computed to a step-change in temperature/PCO2. Computations for frog (Rana catesbeiana) striated muscle show that the calculated pHi response on the basis of estimated composition and concentration of cell buffer components, moves along the curve describing the steady-state temperature relationship. No transient away from steady-state alphaIM and carbon dioxide content need be postulated. Applications to turtle (Pseudemys scripta) striated muscle are also explored. These calculations show that ectotherm cells may be capable of responding without appreciable time for adaptation to intracellular acid-base state changes incurred by sudden alteration of body temperature in vivo, given the observed adjustments of blood PCO2 with temperature. | Model studies of intracellular acid-base temperature responses in ectotherms. Measurements of intracellular pH (pHi) in air-breathing ectotherms have only been made in the steady state; these pHi indicate that protein charge state, measured as alpha imidazole (alphaIM), the fractional dissociation of protein histidine imidazole groups, is preserved when ectotherm tissues change temperature in vivo, with related changes in pHi and PCO2. In partial answer to the question of how such tissues are able to avoid disrupting transients to functions sensitive to protein charge states, model studies were carried out to assess the passive intracellular buffer system response to a combined change in body temperature and CO2 partial pressure as occurs in vivo in these species. The cell compartment was modeled as a closed volume of ternary buffer solution, containing protein imidazole (50 mM/1); phosphate (15 mM/1) and CO2-bicarbonate buffer components, permeable only to CO2 and permitted no change in buffer base. Excursions from a steady-state non-equilibrium pHi were computed to a step-change in temperature/PCO2. Computations for frog (Rana catesbeiana) striated muscle show that the calculated pHi response on the basis of estimated composition and concentration of cell buffer components, moves along the curve describing the steady-state temperature relationship. No transient away from steady-state alphaIM and carbon dioxide content need be postulated. Applications to turtle (Pseudemys scripta) striated muscle are also explored. These calculations show that ectotherm cells may be capable of responding without appreciable time for adaptation to intracellular acid-base state changes incurred by sudden alteration of body temperature in vivo, given the observed adjustments of blood PCO2 with temperature. | [
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PMID:10616 | Intracellular buffering of heart and skeletal muscles during the onset of hypercapnia. | Changes in the total CO2 content of tissues were determined in order to characterize variations in intracellular acid-base parameters during the onset of hypercapnia. Within two minutes after an increasement in the CO2 tension of the inspired air of rats, there were large increases in the intracellular bicarbonate concentrations of both cardiac and skeletal muscles. Greater changes occurred in the heart, and its intracellular pH remained near normal during the first hour of hypercapnia; whereas there was an intracellular acidosis in skeletal muscle. This greater capacity of the heart to buffer excess CO2 has been linked to an increased movement of bicarbonate ions into and/or hydrogen ions out of cardiac cells during hypercapnia (Lai et al., 1973c). Yet, the buffer capacity of the heart was not compromised by metabolic acidosis during which there was a greatly reduced extracellular bicarbonate ion concentration and a greatly increased extracellular hydrogen ion concentration. The intracellular pH of the cardiac ventricle was stable following the imposition of a noncarbonic acid load on normocapnic rats. | Intracellular buffering of heart and skeletal muscles during the onset of hypercapnia. Changes in the total CO2 content of tissues were determined in order to characterize variations in intracellular acid-base parameters during the onset of hypercapnia. Within two minutes after an increasement in the CO2 tension of the inspired air of rats, there were large increases in the intracellular bicarbonate concentrations of both cardiac and skeletal muscles. Greater changes occurred in the heart, and its intracellular pH remained near normal during the first hour of hypercapnia; whereas there was an intracellular acidosis in skeletal muscle. This greater capacity of the heart to buffer excess CO2 has been linked to an increased movement of bicarbonate ions into and/or hydrogen ions out of cardiac cells during hypercapnia (Lai et al., 1973c). Yet, the buffer capacity of the heart was not compromised by metabolic acidosis during which there was a greatly reduced extracellular bicarbonate ion concentration and a greatly increased extracellular hydrogen ion concentration. The intracellular pH of the cardiac ventricle was stable following the imposition of a noncarbonic acid load on normocapnic rats. | [
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PMID:10618 | The effect of hepatectomy on the energy state and on acid-base variables of the rat brain. | The influence of hepatectomy on cerebral energy metabolism was studied in rats in which an end-to-side portacaval anastomosis had been performed one week earlier. The hepatectomy gave rise to an exaggeration of the increase in tissue ammonia content resulting from the shunt. Three hours after the hepatectomy there was a fall in tissue glutamate content but no change in alpha-ketoglutarate. The energy state of the tissue, as evaluated from the concentrations of ATP, ADP, and AMP, was unchanged. There was a significant increase in cerebrospinal fluid pH but no change in intracellular pH. | The effect of hepatectomy on the energy state and on acid-base variables of the rat brain. The influence of hepatectomy on cerebral energy metabolism was studied in rats in which an end-to-side portacaval anastomosis had been performed one week earlier. The hepatectomy gave rise to an exaggeration of the increase in tissue ammonia content resulting from the shunt. Three hours after the hepatectomy there was a fall in tissue glutamate content but no change in alpha-ketoglutarate. The energy state of the tissue, as evaluated from the concentrations of ATP, ADP, and AMP, was unchanged. There was a significant increase in cerebrospinal fluid pH but no change in intracellular pH. | [
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PMID:10619 | Microcalorimetric measurements of heat production in human erythrocytes. Heat effect during methylene blue stimulation. | The metabolic activity in human erythrocytes during stimulation with 10(-4) mol/l methylene blue has been studied by a microcalorimetric method. Simultaneous measurements were performed on cells from the same preparation suspended in different media. Mean values for the ratios between heat effect values were 7.1 +/- 1.0, 7.4 +/- 0.8, and 10.2 +/- 1.7 (+/- S.D.) for cells suspended in plasma, serum, and glucose phosphate buffer, respectively. All heat effect values were corrected to pH 7.40 using the correction factor found in the present work (0.4 % per 0.01 pH unit). The present calorimetric results are in qualitative agreement with previous reports of other investigators concerning the stimulating effect of methylene blue and the influence of pH on the pentose phosphate pathway. | Microcalorimetric measurements of heat production in human erythrocytes. Heat effect during methylene blue stimulation. The metabolic activity in human erythrocytes during stimulation with 10(-4) mol/l methylene blue has been studied by a microcalorimetric method. Simultaneous measurements were performed on cells from the same preparation suspended in different media. Mean values for the ratios between heat effect values were 7.1 +/- 1.0, 7.4 +/- 0.8, and 10.2 +/- 1.7 (+/- S.D.) for cells suspended in plasma, serum, and glucose phosphate buffer, respectively. All heat effect values were corrected to pH 7.40 using the correction factor found in the present work (0.4 % per 0.01 pH unit). The present calorimetric results are in qualitative agreement with previous reports of other investigators concerning the stimulating effect of methylene blue and the influence of pH on the pentose phosphate pathway. | [
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PMID:10620 | Effect of the histamine H2-receptor antagonist, cimetidine, on gastric secretion and serum gastrin during insulin infusion in Man. | Cimetidine infusion (100 mg h-1) reduced the acid secretory response to insulin infusion (0.03 units Kg-1h-1) when compared to paired control tests in 6 healthy volunteers. There was no significant difference between cimetidine and control tests in terms of pepsin output or serum gastrin concentrations. Cimetidine also reduced the acid secretory response when administered after 90 minutes of insulin had established a secretory response in extended tests in 3 additional volunteers. Cimetidine may have therapeutic potential in the peptic ulcer diathesis. | Effect of the histamine H2-receptor antagonist, cimetidine, on gastric secretion and serum gastrin during insulin infusion in Man. Cimetidine infusion (100 mg h-1) reduced the acid secretory response to insulin infusion (0.03 units Kg-1h-1) when compared to paired control tests in 6 healthy volunteers. There was no significant difference between cimetidine and control tests in terms of pepsin output or serum gastrin concentrations. Cimetidine also reduced the acid secretory response when administered after 90 minutes of insulin had established a secretory response in extended tests in 3 additional volunteers. Cimetidine may have therapeutic potential in the peptic ulcer diathesis. | [
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PMID:10621 | Effect of gastric hypersecretion on the canine duodenum. | The neutralization of acid introduced into the duodenum has been found to be less intensive in patients with duodenal ulcer than in controls. The present work studied the possibility that chronic gastric hypersecretion injures the duodenal mucosa and thereby influences the neutralization system. Gastric hypersecretion was provoked for 3 weeks in 3 dogs by a daily injection of a gastrin preparation with prolonged effect. After a subcutaneous injection of this preparation given together with a test meal the acidity of both gastric and duodenal contents was found to increase significantly. After the 3 weeks of gastric hypersecretion the pancreatic bicarbonate response to exogenous secretin was unchanged, while the bicarbonate response to duodenal acidification was decreased from 2.03 mEq/30 min to 1.27 mEq/30 min (p less than 0.05), compatible with an impaired secretin release. Also the concentration of lactase, maltase, sucrase, and alkaline phosphatase in mucosal biopsies from the second part of the duodenum was significantly reduced (p less than 0.001). These results indicate that gastric hypersecretion causes mucosal damage in the duodenum and thereby reduces the release of secretin. | Effect of gastric hypersecretion on the canine duodenum. The neutralization of acid introduced into the duodenum has been found to be less intensive in patients with duodenal ulcer than in controls. The present work studied the possibility that chronic gastric hypersecretion injures the duodenal mucosa and thereby influences the neutralization system. Gastric hypersecretion was provoked for 3 weeks in 3 dogs by a daily injection of a gastrin preparation with prolonged effect. After a subcutaneous injection of this preparation given together with a test meal the acidity of both gastric and duodenal contents was found to increase significantly. After the 3 weeks of gastric hypersecretion the pancreatic bicarbonate response to exogenous secretin was unchanged, while the bicarbonate response to duodenal acidification was decreased from 2.03 mEq/30 min to 1.27 mEq/30 min (p less than 0.05), compatible with an impaired secretin release. Also the concentration of lactase, maltase, sucrase, and alkaline phosphatase in mucosal biopsies from the second part of the duodenum was significantly reduced (p less than 0.001). These results indicate that gastric hypersecretion causes mucosal damage in the duodenum and thereby reduces the release of secretin. | [
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PMID:10625 | Enkephalin-induced depression of single neurons in brain areas with opiate receptors--antagonism by naloxone. | Enkephalin, applied microiontophoretically, depressed spontaneous and glutamate-induced firing of single neurons in frontal cortex, caudate nucleus, and periaqueductal gray matter, where enkephalin and high concentrations of opiate receptors are found. Many of the depressions were blocked by the specific narcotic antagonist naloxone. The data are compatible with a neurotransmitter or neuromodulator role for this new brain pentapeptide. | Enkephalin-induced depression of single neurons in brain areas with opiate receptors--antagonism by naloxone. Enkephalin, applied microiontophoretically, depressed spontaneous and glutamate-induced firing of single neurons in frontal cortex, caudate nucleus, and periaqueductal gray matter, where enkephalin and high concentrations of opiate receptors are found. Many of the depressions were blocked by the specific narcotic antagonist naloxone. The data are compatible with a neurotransmitter or neuromodulator role for this new brain pentapeptide. | [
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PMID:10622 | Structural studies on des-pentapeptide (B26-30)-insulin. III. State of aggregation, tyrosyl environment, and peptide backbone conformation in solution. | The three-dimensional structure of des-pentapeptide (B26--30)-insulin (DPI) in solution has been studied by several methods in view of the obvious fact that such knowledge would have much to bear on an understanding of the structure of the receptor-binding site of insulin. (1) The molecular weight of DPI has been studied by the gel filtration method. The results demonstrate that DPI exhibits no self-association behaviour but exists as monomers under the experimental conditions. This enables us to deduce that insulin binds its receptor in the monomeric form; its functional unit is the monomer. (2) The pH difference spectra, denaturation difference spectra, and temperature effect curves have been examined. The results indicate that all three tyrosyl side chains of DPI are unmasked and situated on the surface of the molecule. (3) The UV CD curves of DPI have also been studied. The far UV CD curve of DPI at pH 7.0 is similar to that of insulin, except that the negative value for [iota]220 decreases. This probably demonstrates that the peptide backbone conformation of DPI is very similar to that of insulin, except that it is slightly extended for the former. The near UV CD curve for DPI differs from that for insulin and has an extremum at 266nm as well as a low negative value of [iota]. The assignment of this extremum to Phe and/or -S-S- has been discussed. Taking into consideration the results given in the following papers, it may be concluded that the results of conformation research obtained support our previous working hypothesis that the hydrophobic surface in between the two monomers making up dimeric insulin constitutes a part of the receptor-binding site of insulin. | Structural studies on des-pentapeptide (B26-30)-insulin. III. State of aggregation, tyrosyl environment, and peptide backbone conformation in solution. The three-dimensional structure of des-pentapeptide (B26--30)-insulin (DPI) in solution has been studied by several methods in view of the obvious fact that such knowledge would have much to bear on an understanding of the structure of the receptor-binding site of insulin. (1) The molecular weight of DPI has been studied by the gel filtration method. The results demonstrate that DPI exhibits no self-association behaviour but exists as monomers under the experimental conditions. This enables us to deduce that insulin binds its receptor in the monomeric form; its functional unit is the monomer. (2) The pH difference spectra, denaturation difference spectra, and temperature effect curves have been examined. The results indicate that all three tyrosyl side chains of DPI are unmasked and situated on the surface of the molecule. (3) The UV CD curves of DPI have also been studied. The far UV CD curve of DPI at pH 7.0 is similar to that of insulin, except that the negative value for [iota]220 decreases. This probably demonstrates that the peptide backbone conformation of DPI is very similar to that of insulin, except that it is slightly extended for the former. The near UV CD curve for DPI differs from that for insulin and has an extremum at 266nm as well as a low negative value of [iota]. The assignment of this extremum to Phe and/or -S-S- has been discussed. Taking into consideration the results given in the following papers, it may be concluded that the results of conformation research obtained support our previous working hypothesis that the hydrophobic surface in between the two monomers making up dimeric insulin constitutes a part of the receptor-binding site of insulin. | [
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PMID:10626 | beta-Adrenergic receptor involvement in 6-hydroxydopamine-induced supersensitivity in rat cerebral cortex. | The intraventricular administration of 6-hydroxydopamine, a procedure which destroys noradrenergic nerve terminals in the central nervous system, caused an increase in the density of beta-adrenergic receptors in rat cerebral cortex, without affecting their affinity for isoproterenol. The results suggest that changes in the density of adrenergic receptors are involved in 6-hydroxydopamine-induced supersensitivity at central noradrenergic synapses. | beta-Adrenergic receptor involvement in 6-hydroxydopamine-induced supersensitivity in rat cerebral cortex. The intraventricular administration of 6-hydroxydopamine, a procedure which destroys noradrenergic nerve terminals in the central nervous system, caused an increase in the density of beta-adrenergic receptors in rat cerebral cortex, without affecting their affinity for isoproterenol. The results suggest that changes in the density of adrenergic receptors are involved in 6-hydroxydopamine-induced supersensitivity at central noradrenergic synapses. | [
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PMID:10623 | Structural studies on des-pentapeptide (B26-30)-insulin. IV. A preliminary investigation on the hydrophobic region by employing a fluorescence probe, 1-p-toluidinylnaphthalene-8-sulphonate. | The fluorescnece porperties of 1,8-TNS in relation to the polarity and viscosity of the solvents have been studied and found to be just as useful as those of its positional isomer 2,6-TNS in the capacity of being a fluorescent probe. The properties of the hydrophobic region of insulin, des-pentapeptide (B26-30)- insulin (DPI), bovine plasma albumin, lysozyme, and ovalbumin have been investigated by employing this fluorescent probe. It has been shown that there is a small but definite hydrophobic region in DPI just as in insulin. This suggests that removal of the C-terminal pentapeptide does not impair seriously the hydrophobic structure related to the binding with insulin receptor. However, at physiologic pH, the hydrophobic region of DPI becomes more exposed than that of insulin and its conformation is less stable. As the pH is increased, the local conformation of the DPI molecule probably suffers some distortion, which damages the conformation of the hydrophobic region to a certain extent. In comparison with insulin, the DPI molecule is relatively loose and unstable. | Structural studies on des-pentapeptide (B26-30)-insulin. IV. A preliminary investigation on the hydrophobic region by employing a fluorescence probe, 1-p-toluidinylnaphthalene-8-sulphonate. The fluorescnece porperties of 1,8-TNS in relation to the polarity and viscosity of the solvents have been studied and found to be just as useful as those of its positional isomer 2,6-TNS in the capacity of being a fluorescent probe. The properties of the hydrophobic region of insulin, des-pentapeptide (B26-30)- insulin (DPI), bovine plasma albumin, lysozyme, and ovalbumin have been investigated by employing this fluorescent probe. It has been shown that there is a small but definite hydrophobic region in DPI just as in insulin. This suggests that removal of the C-terminal pentapeptide does not impair seriously the hydrophobic structure related to the binding with insulin receptor. However, at physiologic pH, the hydrophobic region of DPI becomes more exposed than that of insulin and its conformation is less stable. As the pH is increased, the local conformation of the DPI molecule probably suffers some distortion, which damages the conformation of the hydrophobic region to a certain extent. In comparison with insulin, the DPI molecule is relatively loose and unstable. | [
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PMID:10624 | Structural studies on des-pentapeptide (B26-30)-insulin. V. High resolution NMR studies. | Preliminary studies have been made of the 250 MHz nuclear magnetic resonance spectra of both insulin and DPI. Differences have been found between DPI and insulin spectra, which indicate that the splitting off of the B-chain C-terminal pentapeptide from insulin has brought about local changes in the conformation of the protein molecule in solution. It seems that these conformational changes have little effect on the biological activity of the hormone. Many studies have revealed that for insulin molecules in solution, an equilibrium exists between aggregation and dissociation, their state of aggregation bearing a close relationship to the concentration as well as pH of the insulin solution. Changes in the concentration and pH value of DPI solutions do not significantly affect the NMR spectra. But as the concentration and pH of the solution are increased, the methyl regions for valine, leucine, and isoleucine and aromatic regions of the insulin spectra are broadened. All these show that zinc-free DPI molecules probably exist as monomers in solution. | Structural studies on des-pentapeptide (B26-30)-insulin. V. High resolution NMR studies. Preliminary studies have been made of the 250 MHz nuclear magnetic resonance spectra of both insulin and DPI. Differences have been found between DPI and insulin spectra, which indicate that the splitting off of the B-chain C-terminal pentapeptide from insulin has brought about local changes in the conformation of the protein molecule in solution. It seems that these conformational changes have little effect on the biological activity of the hormone. Many studies have revealed that for insulin molecules in solution, an equilibrium exists between aggregation and dissociation, their state of aggregation bearing a close relationship to the concentration as well as pH of the insulin solution. Changes in the concentration and pH value of DPI solutions do not significantly affect the NMR spectra. But as the concentration and pH of the solution are increased, the methyl regions for valine, leucine, and isoleucine and aromatic regions of the insulin spectra are broadened. All these show that zinc-free DPI molecules probably exist as monomers in solution. | [
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PMID:10628 | Ovum aging and pH imbalance as a cause of chromosomal anomalies in the hamster. | Using female hamsters mated in estrus, we have produced triploid embryos as manifestations of pregnancy wastage by combining delays of 3 to 4 hours in ferilization with exposure of the animals to hypoxia. Among the triploid embryos only XXX and XXY karotypes occurred, indicating derivation from XX-containing ova. These findings have relevance to human reproduction. | Ovum aging and pH imbalance as a cause of chromosomal anomalies in the hamster. Using female hamsters mated in estrus, we have produced triploid embryos as manifestations of pregnancy wastage by combining delays of 3 to 4 hours in ferilization with exposure of the animals to hypoxia. Among the triploid embryos only XXX and XXY karotypes occurred, indicating derivation from XX-containing ova. These findings have relevance to human reproduction. | [
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PMID:10629 | Choline administration: activation of tyrosine hydroxylase in dopaminergic neurons of rat brain. | The administration of choline in doses previously shown to elevate brain acetylcholine concentrations also increases the activity of tyrosine hydroxylase in rat caudate nuclei. This response can be blocked by atropine, a muscarinic antagonist. These findings indicate that choline-induced increases in acetylcholine concentrations may be associated with parallel changes in the amount of the neurotransmitter released into synapses. | Choline administration: activation of tyrosine hydroxylase in dopaminergic neurons of rat brain. The administration of choline in doses previously shown to elevate brain acetylcholine concentrations also increases the activity of tyrosine hydroxylase in rat caudate nuclei. This response can be blocked by atropine, a muscarinic antagonist. These findings indicate that choline-induced increases in acetylcholine concentrations may be associated with parallel changes in the amount of the neurotransmitter released into synapses. | [
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PMID:10630 | [Capillary sample and blood gas analysis. Technic and validity]. | The authors have developed a technique of sampling and analysis of capillary blood which they describe here. Applied to 34 patients, it gives excellent correlations, both for PO2-PCO2 and pH. The advantages of capillary methods and their disadvantages are discussed. | [Capillary sample and blood gas analysis. Technic and validity]. The authors have developed a technique of sampling and analysis of capillary blood which they describe here. Applied to 34 patients, it gives excellent correlations, both for PO2-PCO2 and pH. The advantages of capillary methods and their disadvantages are discussed. | [
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PMID:10632 | Skin changes in graft-vs-host disease. | In this review of the clinical and histopathologic manifestations of the graft-vs-host reaction, the characteristic changes in the skin are given particular emphasis, since they are among the earliest and most obvious signs of this syndrome. The acute and chronic forms of graft-vs-host disease are distinguished, with notation of their different dermatologic presentations. The distinctive histopathologic and immunopathologic findings of the graft-vs-host reaction in the skin are presented. Finally, the possible pathogenetic mechanisms which produce the clinical picuture of graft-vs-host disease are discussed. Both T cells and B cells apparently are involved, as are macrophages, but what is primary and what is secondary in the reaction remains to be delineated, as do the respective contributions of donor and host cells. | Skin changes in graft-vs-host disease. In this review of the clinical and histopathologic manifestations of the graft-vs-host reaction, the characteristic changes in the skin are given particular emphasis, since they are among the earliest and most obvious signs of this syndrome. The acute and chronic forms of graft-vs-host disease are distinguished, with notation of their different dermatologic presentations. The distinctive histopathologic and immunopathologic findings of the graft-vs-host reaction in the skin are presented. Finally, the possible pathogenetic mechanisms which produce the clinical picuture of graft-vs-host disease are discussed. Both T cells and B cells apparently are involved, as are macrophages, but what is primary and what is secondary in the reaction remains to be delineated, as do the respective contributions of donor and host cells. | [
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] |
PMID:10633 | The introduction of SI units and the standardisation of laboratory reports: recommendations of the South African Association of Clinical Biochemists. | The change of SI units in laboratory reporting is occurring in South Africa. To assist this process and to ensure uniformity among laboratories, the Recommendations of the South African Association of Clinical Biochemists are presented. Controversial points are discussed and subunits selected. A standardised format of laboratory reports is suggested. | The introduction of SI units and the standardisation of laboratory reports: recommendations of the South African Association of Clinical Biochemists. The change of SI units in laboratory reporting is occurring in South Africa. To assist this process and to ensure uniformity among laboratories, the Recommendations of the South African Association of Clinical Biochemists are presented. Controversial points are discussed and subunits selected. A standardised format of laboratory reports is suggested. | [
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PMID:10634 | The effect of microaggregates in stored blood on canine pulmonary vascular resistance. | Microaggregates have been implicated as a contributory cause of respiratory distress syndrome. Blood flow and resistance changes are compared between the right and left lungs following the selective administration of stored autologous heparinized blood into the left pulmonary artery. Eight dogs were bled 1,160 +/- 47 c.c. over 3 days. Following storage for 5 days the volume, number and size of microaggregates were measured by multichannel particle size analyzer and compared to 14-day-old human blood. Distribution of blood flow and resistance were calculated from data derived from injection of radioactively tagged microspheres into the right atrium and determination of cardiac output and pulmonary artery and wedge pressures. These measurements were made during a control period, following resuscitation from a 2 hour hemorrhagic shock period with the stored blood and 3 hours after resuscitation. Despite the administration of stored blood with massive amounts of microaggregates into the left pulmonary artery, the distribution of blood flow immediately and 3 hours following resuscitation was the same as in the control period. The pulmonary vascular resistance increased across both lungs but the increase was the same on the left as the right. These data suggest that microaggregates may not be important in the development of the respiratory distress syndrome. | The effect of microaggregates in stored blood on canine pulmonary vascular resistance. Microaggregates have been implicated as a contributory cause of respiratory distress syndrome. Blood flow and resistance changes are compared between the right and left lungs following the selective administration of stored autologous heparinized blood into the left pulmonary artery. Eight dogs were bled 1,160 +/- 47 c.c. over 3 days. Following storage for 5 days the volume, number and size of microaggregates were measured by multichannel particle size analyzer and compared to 14-day-old human blood. Distribution of blood flow and resistance were calculated from data derived from injection of radioactively tagged microspheres into the right atrium and determination of cardiac output and pulmonary artery and wedge pressures. These measurements were made during a control period, following resuscitation from a 2 hour hemorrhagic shock period with the stored blood and 3 hours after resuscitation. Despite the administration of stored blood with massive amounts of microaggregates into the left pulmonary artery, the distribution of blood flow immediately and 3 hours following resuscitation was the same as in the control period. The pulmonary vascular resistance increased across both lungs but the increase was the same on the left as the right. These data suggest that microaggregates may not be important in the development of the respiratory distress syndrome. | [
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PMID:10636 | Purification and properties of human factor IXa. | Human factor IXa was purified 5,000-fold from serum by ion exchange chromatography. The preparation was free from other clotting factors. Both pH sensitivity and heat stability of purified factor IXa appeared to be different from those of factor IX in the plasma. The molecular weight of human factor IXa is 80,000 as estimated from gel-filtration experiments. Modification of seryl or histidyl side chains abolished the activity of factor IXa. | Purification and properties of human factor IXa. Human factor IXa was purified 5,000-fold from serum by ion exchange chromatography. The preparation was free from other clotting factors. Both pH sensitivity and heat stability of purified factor IXa appeared to be different from those of factor IX in the plasma. The molecular weight of human factor IXa is 80,000 as estimated from gel-filtration experiments. Modification of seryl or histidyl side chains abolished the activity of factor IXa. | [
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PMID:10637 | Reactivity of fibrinogen crosslinking sites in the absence of thrombin. | The reactivity of fibrinogen crosslinking sites with thrombin-free, preactivated factor XIII (F. XIIIa) was investigated under different conditions such as increased ionic strength, presence of urea, protamine sulfate (PS) or of varying concentrations of monodansylcadaverine (MDC). Crosslinking and incorporation of MDC into fibrinogen or fibrin gamma- and alpha-chains were evaluated by SDS-polyacrylamide gel electrophoresis. According to our results, rates of crosslinking of, and of MDC incorporation into, both gamma- and alpha-chains of fibrinogen were low under physiological conditions; they were not significantly influenced by the presence of either 1.0 M NaCl or 1.0 M urea. In contrast, 0.01% PS precipitated fibrinogen, and, simultaneously, significantly increased the rates of crosslinking and of MDC incorporation into both gamma- and alpha-chains. MDC, at concentrations above approximately 6 mM, also precipitated fibrinogen, and, up to a concentration of about 9 mM, markedly enhanced the reactivity of acceptor crosslinking sites. Our results suggest that solubility of fibrinogen and the conformational arrangement of its subunit chains are closely interdependent; the reactivity of crosslinking sites with F. XIIIa seems to be a function of this conformational state. | Reactivity of fibrinogen crosslinking sites in the absence of thrombin. The reactivity of fibrinogen crosslinking sites with thrombin-free, preactivated factor XIII (F. XIIIa) was investigated under different conditions such as increased ionic strength, presence of urea, protamine sulfate (PS) or of varying concentrations of monodansylcadaverine (MDC). Crosslinking and incorporation of MDC into fibrinogen or fibrin gamma- and alpha-chains were evaluated by SDS-polyacrylamide gel electrophoresis. According to our results, rates of crosslinking of, and of MDC incorporation into, both gamma- and alpha-chains of fibrinogen were low under physiological conditions; they were not significantly influenced by the presence of either 1.0 M NaCl or 1.0 M urea. In contrast, 0.01% PS precipitated fibrinogen, and, simultaneously, significantly increased the rates of crosslinking and of MDC incorporation into both gamma- and alpha-chains. MDC, at concentrations above approximately 6 mM, also precipitated fibrinogen, and, up to a concentration of about 9 mM, markedly enhanced the reactivity of acceptor crosslinking sites. Our results suggest that solubility of fibrinogen and the conformational arrangement of its subunit chains are closely interdependent; the reactivity of crosslinking sites with F. XIIIa seems to be a function of this conformational state. | [
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PMID:10638 | Aggregation of platelets and inert particles induced by thrombin. | Thrombin-induced platelet aggregation and release were investigated in washed platelet suspensions and in suspensions of inert particles in order to evaluate the role of fibrinogen-fibrin transformation in aggregometer tracings. Thrombin (0.25-2.0 U/ml) produced two waves of light transmission increase (LTI) in both platelet and inert particle suspensions containing fibrinogen, and concomittantly aggregates were observed under phase microscopy. Without fibrinogen, thrombin induced rapid release of platelet ADP but failed to cause second wave of LTI. The kinetics of LTI in platelet and inert particle systems were related to both thrombin and fibrinogen concentrations. A rapid second wave of LTI could be produced by direct interaction of thrombin-treated platelets or inert particles with polymerizing fibrin, and was inhibited by sodium sulfite and low pH of 5.1 which prevent fibrin monomer polymerization. No fibrin strands were noted in platelet aggregates fixed at the completion of the second wave of LTI. Apyrase and PGE1 inhibited the rate of first but not that of second wave LTI. The results suggest that the release of platelet ADP induced by thrombin primarily affects the first phase aggregation, and the second phase may result from interaction of thrombin-exposed platelets and polymerizing fibrin. Thus, the blood coagulation mechanism may be directly involved in platelet aggregation. | Aggregation of platelets and inert particles induced by thrombin. Thrombin-induced platelet aggregation and release were investigated in washed platelet suspensions and in suspensions of inert particles in order to evaluate the role of fibrinogen-fibrin transformation in aggregometer tracings. Thrombin (0.25-2.0 U/ml) produced two waves of light transmission increase (LTI) in both platelet and inert particle suspensions containing fibrinogen, and concomittantly aggregates were observed under phase microscopy. Without fibrinogen, thrombin induced rapid release of platelet ADP but failed to cause second wave of LTI. The kinetics of LTI in platelet and inert particle systems were related to both thrombin and fibrinogen concentrations. A rapid second wave of LTI could be produced by direct interaction of thrombin-treated platelets or inert particles with polymerizing fibrin, and was inhibited by sodium sulfite and low pH of 5.1 which prevent fibrin monomer polymerization. No fibrin strands were noted in platelet aggregates fixed at the completion of the second wave of LTI. Apyrase and PGE1 inhibited the rate of first but not that of second wave LTI. The results suggest that the release of platelet ADP induced by thrombin primarily affects the first phase aggregation, and the second phase may result from interaction of thrombin-exposed platelets and polymerizing fibrin. Thus, the blood coagulation mechanism may be directly involved in platelet aggregation. | [
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PMID:10643 | Human immunity to rat antigens. II. Immune responses in dialysis patients. | The immune status of 35 patients with renal failure was studied shortly after they had commenced treatment by chronic haemodialysis to see if a group with poor immunological responses could be identified. Of 27 patients who were unimmunised to start with, only two developed lymphocytoxic antibodies after a year of treatment. The routine immunological tests that were carried out on these patients failed to predict which of them would develop antibodies, and the values that were obtained for the group of cytotoxic negative patients were no different from those obtained for the two patients who became immunised and six others who had previously rejected a kidney transplant. By using a new test that measured cellular immunity to rat antigens, eight patients could be identified as "poor responders." These individuals had in addition failed to develop cytotoxic antibodies during dialysis, had serum IgG levels that were significantly lower than normal, and were uniformly unresponsive to purified protein derivative. This group of patients might be a favoruable one to transplant. | Human immunity to rat antigens. II. Immune responses in dialysis patients. The immune status of 35 patients with renal failure was studied shortly after they had commenced treatment by chronic haemodialysis to see if a group with poor immunological responses could be identified. Of 27 patients who were unimmunised to start with, only two developed lymphocytoxic antibodies after a year of treatment. The routine immunological tests that were carried out on these patients failed to predict which of them would develop antibodies, and the values that were obtained for the group of cytotoxic negative patients were no different from those obtained for the two patients who became immunised and six others who had previously rejected a kidney transplant. By using a new test that measured cellular immunity to rat antigens, eight patients could be identified as "poor responders." These individuals had in addition failed to develop cytotoxic antibodies during dialysis, had serum IgG levels that were significantly lower than normal, and were uniformly unresponsive to purified protein derivative. This group of patients might be a favoruable one to transplant. | [
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PMID:10644 | Studies on a systemic xenogeneic graft-versus-host reaction model in newborn mice. | A xenogeneic graft-versus-host reaction model is described, evoked in neonatal mice by injection of rat spleen cells, and registered as splenomegaly at day 7. The following arguments are given as support for the idea that the reaction is indeed a graft-versus-host reaction: only living rat cells can give the reaction; rat cells treated with antilymphocyte serum cannot do so. The reaction is of almost the same strength in mice which have thymus dysplasia and are probably incapable of mounting a host-versus-graft reaction. Pretreatment of the grafted cells with mitomycin C, which abolishes the cells' capacity for DNA synthesis and proliferation, also eliminates their capacity to cause splenomegaly. This is probably because the grafted cell clone, reactive to mouse antigens, is small and has to be expended in order to be effective. Dividing rat cells have been demonstrated by chromosome studies in the enlarged mouse spleens 2--6 days after grafting. | Studies on a systemic xenogeneic graft-versus-host reaction model in newborn mice. A xenogeneic graft-versus-host reaction model is described, evoked in neonatal mice by injection of rat spleen cells, and registered as splenomegaly at day 7. The following arguments are given as support for the idea that the reaction is indeed a graft-versus-host reaction: only living rat cells can give the reaction; rat cells treated with antilymphocyte serum cannot do so. The reaction is of almost the same strength in mice which have thymus dysplasia and are probably incapable of mounting a host-versus-graft reaction. Pretreatment of the grafted cells with mitomycin C, which abolishes the cells' capacity for DNA synthesis and proliferation, also eliminates their capacity to cause splenomegaly. This is probably because the grafted cell clone, reactive to mouse antigens, is small and has to be expended in order to be effective. Dividing rat cells have been demonstrated by chromosome studies in the enlarged mouse spleens 2--6 days after grafting. | [
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PMID:10648 | Correlation of graft-versus-host mortality and positive CML assay in the mouse. | GVH mortality was encountered in each of six parental-F1 hybrid combinations with antigenic disparity sufficient to cause strong positive CML. Mortality was encountered in only one of nine combinations in which CML is negative (or weak). The CML assay may thus be useful, but is not perfect, in prediction of GVH mortality. Of the eight CML-negative, GVH nonlethal combinations, three were MLC positive and also activated donor T-cell proliferation in vivo. | Correlation of graft-versus-host mortality and positive CML assay in the mouse. GVH mortality was encountered in each of six parental-F1 hybrid combinations with antigenic disparity sufficient to cause strong positive CML. Mortality was encountered in only one of nine combinations in which CML is negative (or weak). The CML assay may thus be useful, but is not perfect, in prediction of GVH mortality. Of the eight CML-negative, GVH nonlethal combinations, three were MLC positive and also activated donor T-cell proliferation in vivo. | [
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PMID:10655 | Properties of 3',5'-cyclic-AMP phosphodiesterase from Paragonimus africanus metacercariae. | 3',5'-Cyclic-AMP 5'-nucleotidohydrolase (cAMP phosphodiesterase, EC 3.1.4.17) was partial purified from metacercariae of Paragonimus africanus. The enzyme activity absolutely depends on Mg2 or Mn2+. The pH-optimum of the cAMP phosphidiesterase was found at pH 8.0. The Michaelis constant for cAMP was determined to be 5 X 10(-6) M. Papaverine deoxyadenosine, theophylline and adenosine were found to be competitive inhibitors of the enzyme activity. The inhibitor constants were calculated to be 13 X 10(-6)M, 25 X 10(-5)M, and 35 X 10(-5)M, and 85 X 10(-5)M,respectively. The molecular weight of the cAMP phosphodiesterase was estimated to be about 40 000 by gel filtration. | Properties of 3',5'-cyclic-AMP phosphodiesterase from Paragonimus africanus metacercariae. 3',5'-Cyclic-AMP 5'-nucleotidohydrolase (cAMP phosphodiesterase, EC 3.1.4.17) was partial purified from metacercariae of Paragonimus africanus. The enzyme activity absolutely depends on Mg2 or Mn2+. The pH-optimum of the cAMP phosphidiesterase was found at pH 8.0. The Michaelis constant for cAMP was determined to be 5 X 10(-6) M. Papaverine deoxyadenosine, theophylline and adenosine were found to be competitive inhibitors of the enzyme activity. The inhibitor constants were calculated to be 13 X 10(-6)M, 25 X 10(-5)M, and 35 X 10(-5)M, and 85 X 10(-5)M,respectively. The molecular weight of the cAMP phosphodiesterase was estimated to be about 40 000 by gel filtration. | [
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PMID:10657 | [Hydrogen ion activity in the cell]. | Literature data and results of our experiments evidence for a heterogenous hydrogen distribution in cells. Intracellular pH should be regarded as a mean activity of hydrogen ions which is the sum of activities in different phases of a cell. Intracellular pH value does not depend on the transmembrane action potential difference, and is resistant to respiratory and metabolic disorders of acid-base equilibrium in the body. It also slightly changes with changing the electrolyte composition and pH of the medium and is not influenced by metabolic inhibitors. A low hydrogen activity in the cell has a certain functional significance. The pH stability is ensured by a number of regulatory mechanism: the buffer properties of the protoplasm itself, and the active hydrogen transport into the medium. Hydrogen released from cells is supposed to be connected with functioning of a specific respiratory chain of superficial protoplasmic membranes. | [Hydrogen ion activity in the cell]. Literature data and results of our experiments evidence for a heterogenous hydrogen distribution in cells. Intracellular pH should be regarded as a mean activity of hydrogen ions which is the sum of activities in different phases of a cell. Intracellular pH value does not depend on the transmembrane action potential difference, and is resistant to respiratory and metabolic disorders of acid-base equilibrium in the body. It also slightly changes with changing the electrolyte composition and pH of the medium and is not influenced by metabolic inhibitors. A low hydrogen activity in the cell has a certain functional significance. The pH stability is ensured by a number of regulatory mechanism: the buffer properties of the protoplasm itself, and the active hydrogen transport into the medium. Hydrogen released from cells is supposed to be connected with functioning of a specific respiratory chain of superficial protoplasmic membranes. | [
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PMID:10664 | In situ dissolution of ureteral calculus. | An obstructing uric acid calculus was successfully managed by dissolution in situ. The methods used are described in detail. Perhaps not applicable in all cases, the ease of the procedure makes it worth considering especially in patients at high risk for open operative intervention. | In situ dissolution of ureteral calculus. An obstructing uric acid calculus was successfully managed by dissolution in situ. The methods used are described in detail. Perhaps not applicable in all cases, the ease of the procedure makes it worth considering especially in patients at high risk for open operative intervention. | [
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PMID:10665 | [Activity and variability of aminopeptidases and gamma-glutamyl transpeptidase of the cutaneous mucous membrane in the cow's rumen]. | The authors studied the activity, chromatographic and electrophoretic distribution of leucylarylamidase, cystinamino peptidase, and gamma-glutamyl transpeptidase of the cytoplasmatic fraction of cow's rumen mucous membrane homogenate. The results of comparative analysis draw attention to the existence of a certain number of the molecular forms of the enzymes studied, to the activation of leucylarylamidase by Co2+, cystinamino peptidase by Co2+ and Ca2+. The possible functions of the amino peptidases and transpeptidase of glutamic acid in the metabolism of nitrogen compounds of the type of peptides, amino acids, and their amides, are discussed in the study. | [Activity and variability of aminopeptidases and gamma-glutamyl transpeptidase of the cutaneous mucous membrane in the cow's rumen]. The authors studied the activity, chromatographic and electrophoretic distribution of leucylarylamidase, cystinamino peptidase, and gamma-glutamyl transpeptidase of the cytoplasmatic fraction of cow's rumen mucous membrane homogenate. The results of comparative analysis draw attention to the existence of a certain number of the molecular forms of the enzymes studied, to the activation of leucylarylamidase by Co2+, cystinamino peptidase by Co2+ and Ca2+. The possible functions of the amino peptidases and transpeptidase of glutamic acid in the metabolism of nitrogen compounds of the type of peptides, amino acids, and their amides, are discussed in the study. | [
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PMID:10666 | [Effectiveness of various barbiturates in chickens of different ages]. | Phenobarbital, allobarbital, and pentobarbital in the doses of 40 and 80 mg per 1 kg body mass were applied intramuscularly to groups of the cockerels of the WL breed at the age of two days, one, two, and six weeks (each group had ten birds) and to eight-week-old WL cockerels in groups of five birds. The methods of clinical observation and repeated determination of the response of the animals to sonic stimuli and contact stimuli, and the evaluation of the quality of some reflexes (particularly the spontaneous position of the body and the correction of the lateral position) were used for the study of suppression evoked by the applied barbiturates. Sleep occurred first after the application of pentobarbital (sooner in younger age groups). The latest beginning of sleep was observed after phenobarbital; in the latter case, sleep was hard to evaluate because it was not very deep. The time of sleep had the longest duration after allobarbital (only in the eight-week-old sleep was longer after pentobarbital), and the shortest after phenobarbital; there were also differences in the duration of sleep between the age groups of birds. The pentobarbital dose of 80 mg kg-1 of body mass killed birds in the three youngest age groups )in the two-day-old it killed nine of ten birds, in the one-week-old eight of ten birds, and in the two-week-old two of ten birds). The differences in the effectiveness of the applied barbiturates in two doses per unit of body mass were related to the age of the animals, even in the cases of the shortest age intervals between individual groups. Very high interspecies differences ensue from a comparison with the doses of these barbiturates usually applied to man. | [Effectiveness of various barbiturates in chickens of different ages]. Phenobarbital, allobarbital, and pentobarbital in the doses of 40 and 80 mg per 1 kg body mass were applied intramuscularly to groups of the cockerels of the WL breed at the age of two days, one, two, and six weeks (each group had ten birds) and to eight-week-old WL cockerels in groups of five birds. The methods of clinical observation and repeated determination of the response of the animals to sonic stimuli and contact stimuli, and the evaluation of the quality of some reflexes (particularly the spontaneous position of the body and the correction of the lateral position) were used for the study of suppression evoked by the applied barbiturates. Sleep occurred first after the application of pentobarbital (sooner in younger age groups). The latest beginning of sleep was observed after phenobarbital; in the latter case, sleep was hard to evaluate because it was not very deep. The time of sleep had the longest duration after allobarbital (only in the eight-week-old sleep was longer after pentobarbital), and the shortest after phenobarbital; there were also differences in the duration of sleep between the age groups of birds. The pentobarbital dose of 80 mg kg-1 of body mass killed birds in the three youngest age groups )in the two-day-old it killed nine of ten birds, in the one-week-old eight of ten birds, and in the two-week-old two of ten birds). The differences in the effectiveness of the applied barbiturates in two doses per unit of body mass were related to the age of the animals, even in the cases of the shortest age intervals between individual groups. Very high interspecies differences ensue from a comparison with the doses of these barbiturates usually applied to man. | [
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PMID:10684 | Microsomal styrene mono-oxygenase and styrene epoxide hydrase activities in rats. | 1. Styrene epoxide formation and styrene epoxide hydration have been studied in liver, lung, kidney, heart, spleen and brain of female and male rats. 2. Styrene epoxide formation is NADPH-dependent although it is enhanced when NADH is added together with NADP. This enzymic activity is inhibited by metyrapone and SKF 525-A but not by the effective inhibitors of epoxide hydrase, 1,2-epoxy-3,3,3-trichloropropene and cyclohexene oxide. 3. Known inducers of liver microsomal mono-oxygenases show a different activity on the two enzymes. Phenobarbital increases both formation and hydration of styrene epoxide; and carbamazepine increase the hydration but not the formation of styrene epoxide; a steroid contraceptive combination (lynestrenol+ mestranol) increases styrene epoxide formation while it inhibits epoxide hydrase; 3-methylcholanthrene does not affect either of the activities. | Microsomal styrene mono-oxygenase and styrene epoxide hydrase activities in rats. 1. Styrene epoxide formation and styrene epoxide hydration have been studied in liver, lung, kidney, heart, spleen and brain of female and male rats. 2. Styrene epoxide formation is NADPH-dependent although it is enhanced when NADH is added together with NADP. This enzymic activity is inhibited by metyrapone and SKF 525-A but not by the effective inhibitors of epoxide hydrase, 1,2-epoxy-3,3,3-trichloropropene and cyclohexene oxide. 3. Known inducers of liver microsomal mono-oxygenases show a different activity on the two enzymes. Phenobarbital increases both formation and hydration of styrene epoxide; and carbamazepine increase the hydration but not the formation of styrene epoxide; a steroid contraceptive combination (lynestrenol+ mestranol) increases styrene epoxide formation while it inhibits epoxide hydrase; 3-methylcholanthrene does not affect either of the activities. | [
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PMID:10685 | [Absorption, distribution and excretion of (quinuclidinyl-3 methyl)-10-phenothiazine (LM 209), a new antihistamine]. | 1. The absorption, distribution and elimination of 10-(3-quinuclidinylmethyl)-phenothiazine (LM 209) were studied in the rat and dog after oral or intravenous administration of the 35S-labelled molecule. 2. Determinations of radioactivity in the rat and dog confirmed absorption and showed that the blood levels increase in proportion to the dose but remain very low compared with tissue concentrations. These were highest in the liver and lung and persisted at high level for more than 6 h after dosage. 3. Excretion of radioactivity was by the urinary and faecal routes. The high level of radioactivity in faeces resulted mainly from biliary excretion which was accompanied by much entero-hepatic circulation. 4. The prolonged retention of LM 209, due to binding to blood and tissue proteins and to entero-hepatic circulation, did not lead to noticeable accumulation of the drug after repeated doses. 5. The difference in the intracellular distribution of LM 209 and phenothiazine shows the importance of the quinuclidine N-subsitution on the phenothiazine ring, and results in a greater affinity to sub-cellular particulate fractions (nuclei, mitochondria, microsomes). | [Absorption, distribution and excretion of (quinuclidinyl-3 methyl)-10-phenothiazine (LM 209), a new antihistamine]. 1. The absorption, distribution and elimination of 10-(3-quinuclidinylmethyl)-phenothiazine (LM 209) were studied in the rat and dog after oral or intravenous administration of the 35S-labelled molecule. 2. Determinations of radioactivity in the rat and dog confirmed absorption and showed that the blood levels increase in proportion to the dose but remain very low compared with tissue concentrations. These were highest in the liver and lung and persisted at high level for more than 6 h after dosage. 3. Excretion of radioactivity was by the urinary and faecal routes. The high level of radioactivity in faeces resulted mainly from biliary excretion which was accompanied by much entero-hepatic circulation. 4. The prolonged retention of LM 209, due to binding to blood and tissue proteins and to entero-hepatic circulation, did not lead to noticeable accumulation of the drug after repeated doses. 5. The difference in the intracellular distribution of LM 209 and phenothiazine shows the importance of the quinuclidine N-subsitution on the phenothiazine ring, and results in a greater affinity to sub-cellular particulate fractions (nuclei, mitochondria, microsomes). | [
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PMID:10686 | Metronidazole (Flagyl): degradation by the intestinal flora. | 1. Metronidazole (Flagyl) is reduced exponentially by the contents of the rat caecum in the absence of oxygen. The rate of removal is highest at pH 7 and 37 degrees. 2. Reduction of the drug is inhibited by boiling of the caecal contents, CHCl3, Cu2+, Ag+, azodicarboxylic acid bis-dimethylamide, p-chloromercuric benzoate, N-ethylmaleimide and 4,4,4-trifluoro-1,2-thienyl-1,3-butanedione. Nitrate, ethanol (3%), CO, phenol and amytal did not affect the rate of reduction. 3. It is concluded that iron-sulphur systems are involved in degradation of the drug. | Metronidazole (Flagyl): degradation by the intestinal flora. 1. Metronidazole (Flagyl) is reduced exponentially by the contents of the rat caecum in the absence of oxygen. The rate of removal is highest at pH 7 and 37 degrees. 2. Reduction of the drug is inhibited by boiling of the caecal contents, CHCl3, Cu2+, Ag+, azodicarboxylic acid bis-dimethylamide, p-chloromercuric benzoate, N-ethylmaleimide and 4,4,4-trifluoro-1,2-thienyl-1,3-butanedione. Nitrate, ethanol (3%), CO, phenol and amytal did not affect the rate of reduction. 3. It is concluded that iron-sulphur systems are involved in degradation of the drug. | [
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PMID:10687 | Mechanism of 2-naphthylamine oxidation catalysed by pig liver microsomes. | 1. In pig liver microsomes 2-naphthylamine-dependent NADPH oxidation, oxygen reduction, and hydroxylamine formation are linear with time for several minutes. A sharp increase in NADPH oxidation and oxygen uptake then coincides with an abrupt loss of hydroxylamine from the medium. 2. The initial rate of 2-naphthylamine N-oxidation correlates with the microsomal concentration of mixed-function amine oxidase and the extent of linear accumulation of hydroxylamine is dependent on microsomal NADPH-cytochrome c reductase activity and concentration of lipid (microsomes). 3. Antisera to NADPH-cytochrome c reductase markedly decreased hydroxylamine accumulation during incubation but had no effect on the rate of 2-naphthylamine N-oxidation. 4. A system duplicating all of the kinetic properties of the microsomal 2-naphthylamine oxidase was constructed with two purified flavoproteins, (mixed-function amine oxidase and NADPH-cytochrome c reductase) and a lipid phase (erythrocyte ghosts or synthetic lecithin liposomes). 5. By independently varying the concentrations of each component in the reconstituted system, the contribution of each to the observed kinetics was defined. 6. In addition to the initial N-oxidation of 2-naphthylamine, at least six other reactions contribute to the kinetic patterns of 2-naphthylamine oxidation catalysed by the reconstituted system. | Mechanism of 2-naphthylamine oxidation catalysed by pig liver microsomes. 1. In pig liver microsomes 2-naphthylamine-dependent NADPH oxidation, oxygen reduction, and hydroxylamine formation are linear with time for several minutes. A sharp increase in NADPH oxidation and oxygen uptake then coincides with an abrupt loss of hydroxylamine from the medium. 2. The initial rate of 2-naphthylamine N-oxidation correlates with the microsomal concentration of mixed-function amine oxidase and the extent of linear accumulation of hydroxylamine is dependent on microsomal NADPH-cytochrome c reductase activity and concentration of lipid (microsomes). 3. Antisera to NADPH-cytochrome c reductase markedly decreased hydroxylamine accumulation during incubation but had no effect on the rate of 2-naphthylamine N-oxidation. 4. A system duplicating all of the kinetic properties of the microsomal 2-naphthylamine oxidase was constructed with two purified flavoproteins, (mixed-function amine oxidase and NADPH-cytochrome c reductase) and a lipid phase (erythrocyte ghosts or synthetic lecithin liposomes). 5. By independently varying the concentrations of each component in the reconstituted system, the contribution of each to the observed kinetics was defined. 6. In addition to the initial N-oxidation of 2-naphthylamine, at least six other reactions contribute to the kinetic patterns of 2-naphthylamine oxidation catalysed by the reconstituted system. | [
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PMID:10688 | Production physiology and properties of a novel fungal fibrinolytic enzyme. | A potent extracellular fibrinolytic enzyme was obtained from cultures of the imperfect fungus Fusarium semitectum under certain growth conditions. Nitrate addition to cultures increased enzyme production. The enzyme showed a versatile proteolytic activity against several protein substrates including casein, gelatin, haemoglobin, bovine serum albumin, and fibrin from both buffalo and human sources. Optimal fibrinolysis occurred at pH values around 7.0. The fibrinolytic activity exhibited marked heat stability in enzyme samples heated at 60 degrees C, and retained more than 40% of its activity in samples heated to 100 degrees C for 10 min. Fibrinolysis proceeded optimally in the temperature range between 50--60 degrees C. Copper ions significantly activated the enzyme. Other biochemical properties are also reported. | Production physiology and properties of a novel fungal fibrinolytic enzyme. A potent extracellular fibrinolytic enzyme was obtained from cultures of the imperfect fungus Fusarium semitectum under certain growth conditions. Nitrate addition to cultures increased enzyme production. The enzyme showed a versatile proteolytic activity against several protein substrates including casein, gelatin, haemoglobin, bovine serum albumin, and fibrin from both buffalo and human sources. Optimal fibrinolysis occurred at pH values around 7.0. The fibrinolytic activity exhibited marked heat stability in enzyme samples heated at 60 degrees C, and retained more than 40% of its activity in samples heated to 100 degrees C for 10 min. Fibrinolysis proceeded optimally in the temperature range between 50--60 degrees C. Copper ions significantly activated the enzyme. Other biochemical properties are also reported. | [
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PMID:10689 | [Cleavage of alpha-L-arabinofuranoside, beta-D-glucopyranoside and beta-cellobioside of 4-nitrophenol by enzymes of various fungi - a contribution to increase the selectivity of tumor therapy]. | To carry out long-term experiments as part of a therapy concept of malignant tumours using inactive transport forms of cancerostatic substances and their specific cleavage in the acidic pH region of the tumours by application of extraneous enzymes, we require enzymes with similar catalytic and pharmacokinetic properties which differ from each other in immunological respect. In the search for such enzymes, the alpha-L-arabinofuranosidases from 12 different fungi, among them 9 basidiomycetes, were studied. The enzymes mentioned were demonstrable in all fungi. Optimum pH values ranged between 2.5 and 5.5. The Km values for the cleavage of alpha-L-arabinofuranoside were, in most cases, 0.5 to 1.8 moles-liter-1-10(-3). With regard to pH dependence, the alpha-L-arabinofuranosidases of most of the fungi investigated proved adequate for the long-term trials envisaged. 4-nitrophenyl-beta-D-glucopyranoside and -beta-cellobioside were also cleaved by enzyme preparations of all the 11 fungi investigated. The beta-D-glucopyranosidases showed a less favourable pH dependence than the alpha-L-arabinofuranosidases. The cleavage of 4-nitrophenyl-beta-cellobioside, on the contrary, showed mostly a comparatively favourable pH dependence. On the basis of the coinciding optimal pH values and the occurrence of 4-nitrophenyl-beta-D-glucopyranoside as an intermediate product in the cleavage of the corresponding cellobioside, we assume that both substrates are cleaved by beta-glucosidase. Because the occurrence of the glucoside during the cleavage of cellobioside is undesirable for the therapeutic trial, a method is proposed for selection of an appropriate cellobioside splitting enzyme basing on the present studies and the relevant literature. | [Cleavage of alpha-L-arabinofuranoside, beta-D-glucopyranoside and beta-cellobioside of 4-nitrophenol by enzymes of various fungi - a contribution to increase the selectivity of tumor therapy]. To carry out long-term experiments as part of a therapy concept of malignant tumours using inactive transport forms of cancerostatic substances and their specific cleavage in the acidic pH region of the tumours by application of extraneous enzymes, we require enzymes with similar catalytic and pharmacokinetic properties which differ from each other in immunological respect. In the search for such enzymes, the alpha-L-arabinofuranosidases from 12 different fungi, among them 9 basidiomycetes, were studied. The enzymes mentioned were demonstrable in all fungi. Optimum pH values ranged between 2.5 and 5.5. The Km values for the cleavage of alpha-L-arabinofuranoside were, in most cases, 0.5 to 1.8 moles-liter-1-10(-3). With regard to pH dependence, the alpha-L-arabinofuranosidases of most of the fungi investigated proved adequate for the long-term trials envisaged. 4-nitrophenyl-beta-D-glucopyranoside and -beta-cellobioside were also cleaved by enzyme preparations of all the 11 fungi investigated. The beta-D-glucopyranosidases showed a less favourable pH dependence than the alpha-L-arabinofuranosidases. The cleavage of 4-nitrophenyl-beta-cellobioside, on the contrary, showed mostly a comparatively favourable pH dependence. On the basis of the coinciding optimal pH values and the occurrence of 4-nitrophenyl-beta-D-glucopyranoside as an intermediate product in the cleavage of the corresponding cellobioside, we assume that both substrates are cleaved by beta-glucosidase. Because the occurrence of the glucoside during the cleavage of cellobioside is undesirable for the therapeutic trial, a method is proposed for selection of an appropriate cellobioside splitting enzyme basing on the present studies and the relevant literature. | [
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PMID:10690 | [On the age dependence of the intracellular proteolysis (author's transl)]. | We report the age dependent changes of the proteolytic capacity of the rat liver at pH 3.0 and pH 6.0. The total proteolytic activity increases during the whole cycle. During the weanling period the specific activity (mug substrate split x min-1 X mg liver protein-1) rises up to values about 30% higher than those of the remaining lifetime. We found the specific activity in old male animals (18 months) to be lower than in younger ones (5 months). These findings are correct for the liver homogenate as well as for the cell fractions. | [On the age dependence of the intracellular proteolysis (author's transl)]. We report the age dependent changes of the proteolytic capacity of the rat liver at pH 3.0 and pH 6.0. The total proteolytic activity increases during the whole cycle. During the weanling period the specific activity (mug substrate split x min-1 X mg liver protein-1) rises up to values about 30% higher than those of the remaining lifetime. We found the specific activity in old male animals (18 months) to be lower than in younger ones (5 months). These findings are correct for the liver homogenate as well as for the cell fractions. | [
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PMID:10691 | [Study of resistance to physical stress in pregnant women: influence of standardized work on cardiovascular system, ventilation, gaseous interchange, carbohydrate metabolism and acid-base balance (author's transl)]. | 10 women in the 12th week of pregnancy were tested with 50 and 60 watts on the bicycle ergometer; 16, in the 38th week of pregnancy and 12 weeks after delivery. Heart rate, blood pressure, O2 intake, CO2 elimination, respiration rate, respiratory volume per minute, lactate, pyruvate, glucose, pCO2, base excess and pH were measured at rest and under stress. Already in the 12th week of pregnancy (SSW), O2 intake and calorie consumption for the same work was significantly higher than in the nonpregnant subjects. Heart rate and blood pressure behaved the same during and outside of pregnancy. In the 38th week of pregnancy, the steady-state was reached later. O2 intake and calorie consumption were significantly increased. In pregnant women, the glucose level decreased about 11 mg% under stress while it remained constant in nonpregnant subjects. In pregnant women, lactate production is significantly higher (26%) during work. Metabolic acidosis cannot be compensated by respiration. The base deficit was significantly larger; pH was reduced. In pregnant women, physical stress produces increased respiration, CO2 consumption and calorie consumption are increased, CO2 deficit is greater and metabolic acidosis develops. | [Study of resistance to physical stress in pregnant women: influence of standardized work on cardiovascular system, ventilation, gaseous interchange, carbohydrate metabolism and acid-base balance (author's transl)]. 10 women in the 12th week of pregnancy were tested with 50 and 60 watts on the bicycle ergometer; 16, in the 38th week of pregnancy and 12 weeks after delivery. Heart rate, blood pressure, O2 intake, CO2 elimination, respiration rate, respiratory volume per minute, lactate, pyruvate, glucose, pCO2, base excess and pH were measured at rest and under stress. Already in the 12th week of pregnancy (SSW), O2 intake and calorie consumption for the same work was significantly higher than in the nonpregnant subjects. Heart rate and blood pressure behaved the same during and outside of pregnancy. In the 38th week of pregnancy, the steady-state was reached later. O2 intake and calorie consumption were significantly increased. In pregnant women, the glucose level decreased about 11 mg% under stress while it remained constant in nonpregnant subjects. In pregnant women, lactate production is significantly higher (26%) during work. Metabolic acidosis cannot be compensated by respiration. The base deficit was significantly larger; pH was reduced. In pregnant women, physical stress produces increased respiration, CO2 consumption and calorie consumption are increased, CO2 deficit is greater and metabolic acidosis develops. | [
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PMID:10697 | [Relationship between thermal treatments of milk and molecular hysteresis of the milk protein system (author's transl)]. | The potentiometric titration curve of milk does not show an equilibrium curve but a hysteresis loop between pH 6.2 und pH 4.8. Hysteresis means thermodynamic metastability and cooperative changes within a structural domain. The structural domain involved in these changes is the casein micelle. Cooperative conformation changes and thermodynamic metastability appear on the resolution of the casein micelle caused by the action of protons. The charge condition of the polypeptide chains is not synchron with the charge supply. The lag depends on the thermal treatment. Therefore the milk protein system can serve as a memory for physical datas. | [Relationship between thermal treatments of milk and molecular hysteresis of the milk protein system (author's transl)]. The potentiometric titration curve of milk does not show an equilibrium curve but a hysteresis loop between pH 6.2 und pH 4.8. Hysteresis means thermodynamic metastability and cooperative changes within a structural domain. The structural domain involved in these changes is the casein micelle. Cooperative conformation changes and thermodynamic metastability appear on the resolution of the casein micelle caused by the action of protons. The charge condition of the polypeptide chains is not synchron with the charge supply. The lag depends on the thermal treatment. Therefore the milk protein system can serve as a memory for physical datas. | [
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PMID:10693 | [Different deoxyribonuclease-activities in bull seminal plasma (author's transl)]. | By means of the in situ assay of deoxyribonucleases in DNA-containing polyacrylamide gels after separation by micro-disc-electrophoresis different deoxyribonucleases are detectable in bull seminal plasma. There are two groups of acid deoxyribonuclease-activities with a pH optimum at pH 5.0, one with a pH optimum at pH 7.4 and an additional one with a pH optimum at pH 8.5. | [Different deoxyribonuclease-activities in bull seminal plasma (author's transl)]. By means of the in situ assay of deoxyribonucleases in DNA-containing polyacrylamide gels after separation by micro-disc-electrophoresis different deoxyribonucleases are detectable in bull seminal plasma. There are two groups of acid deoxyribonuclease-activities with a pH optimum at pH 5.0, one with a pH optimum at pH 7.4 and an additional one with a pH optimum at pH 8.5. | [
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PMID:10695 | [Effect of pregnancy on the functional state of the upper respiratory tracts]. | The author studied the condition of various components responsible for the protective function of the upper respiratory tract mucous membrane as well as the olfactory sensibility in 439 pregnant women. She found certain regularities in the change of the motor, absorbing and secretory activity of the mucous membrane and olfactory sensibility, the calorific effect and the active reaction of the secrete being less characteristic. She emphasizes that the above changes cause the development of respiratory disorders in women during the period of pregnancy. | [Effect of pregnancy on the functional state of the upper respiratory tracts]. The author studied the condition of various components responsible for the protective function of the upper respiratory tract mucous membrane as well as the olfactory sensibility in 439 pregnant women. She found certain regularities in the change of the motor, absorbing and secretory activity of the mucous membrane and olfactory sensibility, the calorific effect and the active reaction of the secrete being less characteristic. She emphasizes that the above changes cause the development of respiratory disorders in women during the period of pregnancy. | [
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PMID:10696 | [Basic principles of physiotherapy for allergic diseases of the otorhinolaryngologic organs]. | Physiotherapy for allergic diseases of otorhinolaryngeal organs is often practiced without taking into consideration the stage of development of the pathologic process, its form and individual peculiarities of its course. This is partly connected with lack of data on the mechanism of the hyposensibilizing effect of physiofactors. In this paper the authors divide the methods of hyposensibilizing physiotherapy into groups according to their prevalent effect on the particular system taking part in the formation of clinical manifestations of the allergic reaction. The authors discuss the expediency of using each group of methods at various stages of the disease according to its form and individual peculiarities of its course. | [Basic principles of physiotherapy for allergic diseases of the otorhinolaryngologic organs]. Physiotherapy for allergic diseases of otorhinolaryngeal organs is often practiced without taking into consideration the stage of development of the pathologic process, its form and individual peculiarities of its course. This is partly connected with lack of data on the mechanism of the hyposensibilizing effect of physiofactors. In this paper the authors divide the methods of hyposensibilizing physiotherapy into groups according to their prevalent effect on the particular system taking part in the formation of clinical manifestations of the allergic reaction. The authors discuss the expediency of using each group of methods at various stages of the disease according to its form and individual peculiarities of its course. | [
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PMID:10701 | [Glucose infusions in suspected chronic placental insufficiency caused by gestosis]. | In this study glucose load and its possible therapeutical efficiency in chronic nutritive insufficiency of the placenta is investigated. Following a definite regime glucose infusions were applied to the mother prepartually as well as subpartually in order to substitute the carbohydrate metabolism of hypotrophic fetuses. Glucose values and the parameters of the acid-base-balance were taken and calculated. The microblood analyses were performed subpartually on the mother and the fetus and postpartually on the newborn. The results gained are discussed and explained with regard to metabolism. The glucose infusion therapy in the form mentioned is suited to influence favourably the fetal hypoglucosemia. | [Glucose infusions in suspected chronic placental insufficiency caused by gestosis]. In this study glucose load and its possible therapeutical efficiency in chronic nutritive insufficiency of the placenta is investigated. Following a definite regime glucose infusions were applied to the mother prepartually as well as subpartually in order to substitute the carbohydrate metabolism of hypotrophic fetuses. Glucose values and the parameters of the acid-base-balance were taken and calculated. The microblood analyses were performed subpartually on the mother and the fetus and postpartually on the newborn. The results gained are discussed and explained with regard to metabolism. The glucose infusion therapy in the form mentioned is suited to influence favourably the fetal hypoglucosemia. | [
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PMID:10702 | Susceptibility of Staphylococcus aureus, Streptococcus pyogenes and Diplococcus pneumoniae to antibiotics. Comparison of patterns in Poland and Federal Republic of Germany. | One hundred and eighty five strains of Gram-positive cocci were tested for susceptibility to 16 antibiotics, including some newer drugs, by agar dilution technique. Of these, 100 strains (50 each isolated in Poland and Germany) were Staphylococcus aureus, 55 Streptococcus pyogenes, and 30 Diplococcus pneumoniae. Previous investigations of streptococci and pneumococci isolated in Poland and Federal Republic of Grmany, revealed no differences in antibiotic-susceptibility patterns in both countries, which was not the case with staphylococci. Present study demonstrates further evidence for existence of differences in antibiotic-sensitivity of staphylococci, depending of their geographical origin, and presents actual state of susceptibility to antibiotics of Streptococcus pyogenes and Diplococcus pneumoniae. | Susceptibility of Staphylococcus aureus, Streptococcus pyogenes and Diplococcus pneumoniae to antibiotics. Comparison of patterns in Poland and Federal Republic of Germany. One hundred and eighty five strains of Gram-positive cocci were tested for susceptibility to 16 antibiotics, including some newer drugs, by agar dilution technique. Of these, 100 strains (50 each isolated in Poland and Germany) were Staphylococcus aureus, 55 Streptococcus pyogenes, and 30 Diplococcus pneumoniae. Previous investigations of streptococci and pneumococci isolated in Poland and Federal Republic of Grmany, revealed no differences in antibiotic-susceptibility patterns in both countries, which was not the case with staphylococci. Present study demonstrates further evidence for existence of differences in antibiotic-sensitivity of staphylococci, depending of their geographical origin, and presents actual state of susceptibility to antibiotics of Streptococcus pyogenes and Diplococcus pneumoniae. | [
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PMID:10703 | Sport training and some activities of human polymorphonuclear leukocyte lysosomes. | The acid phosphatase and protease, neutral protease, bactericidal and mitogenic activities were determined in the polymorphonuclear leukocyte (PMNL) lysosomes of 16 years old boys. The investigated group consisted of 20 intense sport training persons during the last six years, the control one of the same age boys without any sport training. The significant decrease of hydrolase activity has been observed in the lysosomes of the peripheral blood PMNL's of the sport training boys. | Sport training and some activities of human polymorphonuclear leukocyte lysosomes. The acid phosphatase and protease, neutral protease, bactericidal and mitogenic activities were determined in the polymorphonuclear leukocyte (PMNL) lysosomes of 16 years old boys. The investigated group consisted of 20 intense sport training persons during the last six years, the control one of the same age boys without any sport training. The significant decrease of hydrolase activity has been observed in the lysosomes of the peripheral blood PMNL's of the sport training boys. | [
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PMID:10705 | [Enzymatic conversion of tetradecanol in heterogenous phase by yeast-alcohol dehydrogenase]. | Alcohol dehydrogenase from yeast converts long-chain primary alcohols not only in the dissolved state, but also at the surface of undissolved particles. Tetradecanol beads with a defined surface can be produced and employed as model substrate. The reaction rate was determined by the proton release accomplished in the reaction. The initial reaction rate depends on the enzyme concentration. The relation is nonlinear (vi = k-[e]0,4); the numerical value of the exponent (n = 0.4) argues in favour of a reaction occurring at the interface. The Lineweaver-Burk plots become linear if the substrate concentrations are based on the molar surface concentrations of the particles. The pH optimum for the reaction at the surface is displaced by 0.25 pH units towards the alkaline region (compared with ethanol as substrate). The activation energy of the reaction with tetradecanol beads as substrate is 30% lower than that for the ethanol oxydation. | [Enzymatic conversion of tetradecanol in heterogenous phase by yeast-alcohol dehydrogenase]. Alcohol dehydrogenase from yeast converts long-chain primary alcohols not only in the dissolved state, but also at the surface of undissolved particles. Tetradecanol beads with a defined surface can be produced and employed as model substrate. The reaction rate was determined by the proton release accomplished in the reaction. The initial reaction rate depends on the enzyme concentration. The relation is nonlinear (vi = k-[e]0,4); the numerical value of the exponent (n = 0.4) argues in favour of a reaction occurring at the interface. The Lineweaver-Burk plots become linear if the substrate concentrations are based on the molar surface concentrations of the particles. The pH optimum for the reaction at the surface is displaced by 0.25 pH units towards the alkaline region (compared with ethanol as substrate). The activation energy of the reaction with tetradecanol beads as substrate is 30% lower than that for the ethanol oxydation. | [
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PMID:10706 | [Structure-activity relationships of halogenated phenylethanolamine and phenoxypropanolamine]. | 12 compounds from the series of halogenated phenylethanolamines and phenoxypropanolamines were tested at the isolated rabbit jejunum, and the pD2-and pA2-values were determined. All the substances act beta-adrenolytically. Except for 3,4-dichloronoradrenaline, which stimulates the alpha-receptors, all the compounds still have pronounced beta-mimetic effects. The 2,5-dihalogenated phenylethanolamines and phenoxypropanolamines block the beta-receptors at lower concentrations than 2,4-dihalogen derivatives. The weakest beta-adrenolytic effects at the intestine were found with compounds halogenated at the 3,4-position. | [Structure-activity relationships of halogenated phenylethanolamine and phenoxypropanolamine]. 12 compounds from the series of halogenated phenylethanolamines and phenoxypropanolamines were tested at the isolated rabbit jejunum, and the pD2-and pA2-values were determined. All the substances act beta-adrenolytically. Except for 3,4-dichloronoradrenaline, which stimulates the alpha-receptors, all the compounds still have pronounced beta-mimetic effects. The 2,5-dihalogenated phenylethanolamines and phenoxypropanolamines block the beta-receptors at lower concentrations than 2,4-dihalogen derivatives. The weakest beta-adrenolytic effects at the intestine were found with compounds halogenated at the 3,4-position. | [
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PMID:10707 | The binding of noradrenaline to human erythrocytes. | When human erythrocytes are incubated in a suspension medium containing noradrenaline, they take up noradrenaline in a reaction proceeding in two phases. In a rapid first reaction noradrenaline is bound by the cells by adsorption at pH-values above 6.0; this reaction follows Freundlich's isotherms. Subsequently, noradrenaline is taken up much more slowly by transmembranous diffusion into the cells. Neither reaction can be influenced by inhibitors such as N-ethyl maleinimide, ouabain, alpha- or beta-receptor blockers. | The binding of noradrenaline to human erythrocytes. When human erythrocytes are incubated in a suspension medium containing noradrenaline, they take up noradrenaline in a reaction proceeding in two phases. In a rapid first reaction noradrenaline is bound by the cells by adsorption at pH-values above 6.0; this reaction follows Freundlich's isotherms. Subsequently, noradrenaline is taken up much more slowly by transmembranous diffusion into the cells. Neither reaction can be influenced by inhibitors such as N-ethyl maleinimide, ouabain, alpha- or beta-receptor blockers. | [
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PMID:10708 | [Renal excretion of long term sulfonamides under fluid administration and modification of the urinary pH value]. | The renal excretion of sulfaclomide, sulfamerazine and sulfamethoxypyridazine is delayed by increased fluid application in rats. The simultaneous administration of sulfonamides and ammonium chloride or sodium hydrogen carbonate causes, respectively, retardation and acceleration of renal sulfonamide excretion which is consistent with the change in urinary pH value. The retarded renal sulfonamide excretion with increasing diuresis is explained by the ensuing change in the urinary pH value. For clinical uses, a speedy renal excretion of long-time sulfonamides by increased diuresis can be expected only if alkalization of the urine is achieved at the same time. | [Renal excretion of long term sulfonamides under fluid administration and modification of the urinary pH value]. The renal excretion of sulfaclomide, sulfamerazine and sulfamethoxypyridazine is delayed by increased fluid application in rats. The simultaneous administration of sulfonamides and ammonium chloride or sodium hydrogen carbonate causes, respectively, retardation and acceleration of renal sulfonamide excretion which is consistent with the change in urinary pH value. The retarded renal sulfonamide excretion with increasing diuresis is explained by the ensuing change in the urinary pH value. For clinical uses, a speedy renal excretion of long-time sulfonamides by increased diuresis can be expected only if alkalization of the urine is achieved at the same time. | [
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PMID:10709 | On the behaviour of murine lymphocytes after in vitro treatment with acid mucoproteins from human serum. | Seromucoproteins from human serum were isolated by perchloric acid extraction followed by DEAE-Sephadex A-50 ion exchange chromatography. The in vitro pretreatment of spleen leukocytes with this fraction caused a dose-dependent inhibition of graft-versus-host reaction as well as an increase of their electrophoretic mobility, the viability being maintained. On contrary, the pretreatment of mice (prospective spleen cell donors of recipients of sheep red blood cells) with human seromucoproteins had no effect on the gvh-reaction as well as on the agglutinin formation to sheep red blood cells under the given conditions. It is supposed that the suppressive effect after in vitro pretreatment may be attributed to a coating effect of seromucoproteins. The fact that spleen cells pretreated in vitro with seromucoproteins are lysed in presence of complement and antiseromucoprotein antiserum supports our opinion. These findings as well as data from the literature support the hypothesis that local concentrated mucoproteins in the skin graft bed in cases of protractedly surviving skin grafts, in the placenta, and on neoplastic tissues can influence unspecifically the immune response. We hope that the understanding of this mechanism may open new possibilities in prolonging allograft survival time. | On the behaviour of murine lymphocytes after in vitro treatment with acid mucoproteins from human serum. Seromucoproteins from human serum were isolated by perchloric acid extraction followed by DEAE-Sephadex A-50 ion exchange chromatography. The in vitro pretreatment of spleen leukocytes with this fraction caused a dose-dependent inhibition of graft-versus-host reaction as well as an increase of their electrophoretic mobility, the viability being maintained. On contrary, the pretreatment of mice (prospective spleen cell donors of recipients of sheep red blood cells) with human seromucoproteins had no effect on the gvh-reaction as well as on the agglutinin formation to sheep red blood cells under the given conditions. It is supposed that the suppressive effect after in vitro pretreatment may be attributed to a coating effect of seromucoproteins. The fact that spleen cells pretreated in vitro with seromucoproteins are lysed in presence of complement and antiseromucoprotein antiserum supports our opinion. These findings as well as data from the literature support the hypothesis that local concentrated mucoproteins in the skin graft bed in cases of protractedly surviving skin grafts, in the placenta, and on neoplastic tissues can influence unspecifically the immune response. We hope that the understanding of this mechanism may open new possibilities in prolonging allograft survival time. | [
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PMID:10712 | Immunological mechanisms in aspirin hypersensitivity. Studies on the immunogenicity of free aspirin. | Anti-aspiryl antibodies were produced in rabbits and guinea pigs by inoculation of aspirin incorporated in complete or incomplete Freund's adjuvant. These antibodies were readily detected by passive haemagglutination using rabbit erythrocytes incubated with aspirin at alkaline pH. Aspiryl conjugates with ovalbumin, human gamma-globulin, bovine gamma-globulin and rabbit serum were also prepared by incubating the proteins with aspirin at alkaline pH. Aspiryl conjugates prepared by this technique behaved, immunologically, identically with the conjugates prepared from aspirin chloride. By contrast, the molar absorbance at 305 nm of the conjugates prepared from aspirin was about 25 times lower than the molar absorbance of the conjugates prepared from aspirin chloride. Since the absorbance of salicylic acid is about eight times greater than that of aspirin, the conclusion is drawn that the aspiryl/salicylyl ratio is significantly higher in the conjugates prepared by incubating proteins with aspirin at alkaline pH than in the conjugates prepared from aspirin chloride. In parallel experiments, salicylic acid did not induce formation of specific antibodies capable of reacting with aspirin- or salicylic acid-treated red cells. Sera giving positive passive haemagglutination with aspirin-treated erythrocytes did not react with erythrocytes treated with salicylic acid or acetic anhydride. | Immunological mechanisms in aspirin hypersensitivity. Studies on the immunogenicity of free aspirin. Anti-aspiryl antibodies were produced in rabbits and guinea pigs by inoculation of aspirin incorporated in complete or incomplete Freund's adjuvant. These antibodies were readily detected by passive haemagglutination using rabbit erythrocytes incubated with aspirin at alkaline pH. Aspiryl conjugates with ovalbumin, human gamma-globulin, bovine gamma-globulin and rabbit serum were also prepared by incubating the proteins with aspirin at alkaline pH. Aspiryl conjugates prepared by this technique behaved, immunologically, identically with the conjugates prepared from aspirin chloride. By contrast, the molar absorbance at 305 nm of the conjugates prepared from aspirin was about 25 times lower than the molar absorbance of the conjugates prepared from aspirin chloride. Since the absorbance of salicylic acid is about eight times greater than that of aspirin, the conclusion is drawn that the aspiryl/salicylyl ratio is significantly higher in the conjugates prepared by incubating proteins with aspirin at alkaline pH than in the conjugates prepared from aspirin chloride. In parallel experiments, salicylic acid did not induce formation of specific antibodies capable of reacting with aspirin- or salicylic acid-treated red cells. Sera giving positive passive haemagglutination with aspirin-treated erythrocytes did not react with erythrocytes treated with salicylic acid or acetic anhydride. | [
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PMID:10714 | High uptake in the erythrocytes and the spleen of the quaternary dipyridylium salt paraquat injected intravenously in hypotonic solutions. | Intravenous injections of the quaternary dipyridlium salt paraquat (14C-labelled) dissolved in solutions of low tonicity result in a high uptake in the erythrocytes and concomitantly also in the spleen (red pulp), the latter being probably due to phagocytosis of paraquat-containing erythrocytes by the reticuloendothelial system. Higher tonicities of the injected solutions result in a low uptake and the same applies to oral, intraperitoneal and subcutaneous injections. Paraquat was present in the erythrocytes in a non-metabolized form without being bound to membranes or proteins. The uptake in the erythrocytes was not influenced by alterations of the pH or by the preparation of a charge-transfer complex with serotonin in the injection solutions. Chemical alterations of the paraquat in the injection solutions could not be detected. In vitro the uptake of paraquat in the erythrocytes was higher in the haemolysed (and then reconstituted by adding sodium chloride) erythrocyte-ghosts than in the non-haemolysed erythrocytes, as shown by incubations at various tonicities. It is proposed that the intravenous injections of paraquat in hypotonic solutions temporarily alter the membranes of the erythrocytes in the blood-stream and make them permeable to paraquat, possibly, as judged from the in vitro experiments, only during a short period of partial haemolysis. The distribution studies also showed a retention of paraquat in the lungs. In addition paraquat was accumulated in the melanin of the tissues. | High uptake in the erythrocytes and the spleen of the quaternary dipyridylium salt paraquat injected intravenously in hypotonic solutions. Intravenous injections of the quaternary dipyridlium salt paraquat (14C-labelled) dissolved in solutions of low tonicity result in a high uptake in the erythrocytes and concomitantly also in the spleen (red pulp), the latter being probably due to phagocytosis of paraquat-containing erythrocytes by the reticuloendothelial system. Higher tonicities of the injected solutions result in a low uptake and the same applies to oral, intraperitoneal and subcutaneous injections. Paraquat was present in the erythrocytes in a non-metabolized form without being bound to membranes or proteins. The uptake in the erythrocytes was not influenced by alterations of the pH or by the preparation of a charge-transfer complex with serotonin in the injection solutions. Chemical alterations of the paraquat in the injection solutions could not be detected. In vitro the uptake of paraquat in the erythrocytes was higher in the haemolysed (and then reconstituted by adding sodium chloride) erythrocyte-ghosts than in the non-haemolysed erythrocytes, as shown by incubations at various tonicities. It is proposed that the intravenous injections of paraquat in hypotonic solutions temporarily alter the membranes of the erythrocytes in the blood-stream and make them permeable to paraquat, possibly, as judged from the in vitro experiments, only during a short period of partial haemolysis. The distribution studies also showed a retention of paraquat in the lungs. In addition paraquat was accumulated in the melanin of the tissues. | [
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PMID:10711 | Morphology and enzyme aktivity in rat small intestinal epithelium 6 and 12 hrs. after an alkylating agent (cyclophosphamide). | Six and twelve hours after a single i.p. dose of cyclophosphamide (100 mg/kg body weight) the activity of different "brush border enzymes" (maltase, sucrase lactase, alkaline phosphatase, gamma-glutamyl transferase) and of a lysosomal enzyme (acid phosphatase) did not change. In vivo absorption of galactose was not diminished by the treatment. The pattern of response to cyclophosphamide seems to be different in SPF and GF rats. The response of crypt epithelium (cell number, mitotic number, mitotic frequency) was more pronounced in the SPF rats, whereas the villus height only decreased in the GF rats. | Morphology and enzyme aktivity in rat small intestinal epithelium 6 and 12 hrs. after an alkylating agent (cyclophosphamide). Six and twelve hours after a single i.p. dose of cyclophosphamide (100 mg/kg body weight) the activity of different "brush border enzymes" (maltase, sucrase lactase, alkaline phosphatase, gamma-glutamyl transferase) and of a lysosomal enzyme (acid phosphatase) did not change. In vivo absorption of galactose was not diminished by the treatment. The pattern of response to cyclophosphamide seems to be different in SPF and GF rats. The response of crypt epithelium (cell number, mitotic number, mitotic frequency) was more pronounced in the SPF rats, whereas the villus height only decreased in the GF rats. | [
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PMID:10715 | Hypertension in end-stage renal disease. The relationship between blood pressure, plasma renin, plasma renin substrate and exchangeable sodium in chronic hemodialysis patients. | Blood pressure (BP), plasma renin concentration (PRC), plasma renin substrate concentration (PRSC) and exchangeable sodium (ES) have been studied in 27 patients undergoing regular hemodialysis because of end-stage renal disease. PRC was significantly higher in the hypertensive than in the normotensive patients. The pattern of PRSC was similar in the groups of patients but with a marked individual variation. ES was slightly lower in the hypertensives than in the normotensives but the difference was not statistically significant. Multiple regression analysis demonstrated a significant correlation between mean BP, the natural logarithm of PRC and ES, but the effect of ES was negligible. PRC was negatively correlated to ES in all patients, including the hypertensives. These results strongly suggest that the renin-angiotensin system is the most important factor involved in the pathogenesis of hypertension in end-stage renal disease, when sodium balance is adequately controlled. A clinical application of the predictive value of PRC concerning the effect of bilateral nephrectomy on hypertension is outlined. | Hypertension in end-stage renal disease. The relationship between blood pressure, plasma renin, plasma renin substrate and exchangeable sodium in chronic hemodialysis patients. Blood pressure (BP), plasma renin concentration (PRC), plasma renin substrate concentration (PRSC) and exchangeable sodium (ES) have been studied in 27 patients undergoing regular hemodialysis because of end-stage renal disease. PRC was significantly higher in the hypertensive than in the normotensive patients. The pattern of PRSC was similar in the groups of patients but with a marked individual variation. ES was slightly lower in the hypertensives than in the normotensives but the difference was not statistically significant. Multiple regression analysis demonstrated a significant correlation between mean BP, the natural logarithm of PRC and ES, but the effect of ES was negligible. PRC was negatively correlated to ES in all patients, including the hypertensives. These results strongly suggest that the renin-angiotensin system is the most important factor involved in the pathogenesis of hypertension in end-stage renal disease, when sodium balance is adequately controlled. A clinical application of the predictive value of PRC concerning the effect of bilateral nephrectomy on hypertension is outlined. | [
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PMID:10716 | A new pattern of multiple endocrine adenomatosis: chemodectoma, bronchial carcinoid, GH-producing pituitary adenoma, and hyperplasia of the parathyroid glands, and antral and duodenal gastrin cells. | A female patient was found to have a chemodectoma, a GH-producing pituitary tumour and a bronchial carcinoid combined with hyperplasia of the parathyroids and of antral and duodenal gastrin cells. This combination of endocrine tumours and hyperplasias does not fit with the two multiple endocrine adenomatosis syndromes recognized at present. The case stresses the importance of scanning the patient for other endocrine tumours, once one has been diagnosed. | A new pattern of multiple endocrine adenomatosis: chemodectoma, bronchial carcinoid, GH-producing pituitary adenoma, and hyperplasia of the parathyroid glands, and antral and duodenal gastrin cells. A female patient was found to have a chemodectoma, a GH-producing pituitary tumour and a bronchial carcinoid combined with hyperplasia of the parathyroids and of antral and duodenal gastrin cells. This combination of endocrine tumours and hyperplasias does not fit with the two multiple endocrine adenomatosis syndromes recognized at present. The case stresses the importance of scanning the patient for other endocrine tumours, once one has been diagnosed. | [
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PMID:10717 | Multiple endocrine adenomatosis of mixed type. | A case of multiple endocrine adenomatosis (MEA) of mixed type is presented. The syndrome, observed in a 65 year-old female, consisted of multiple neurofibroadenomatosis, medullary thyroid carcinoma, multiple adenomata of the parathyroids, adrenal cortical adenoma and small cell anaplastic bronchogenic carcinoma. Thus, it was composed of type 1 as well as of type 2 MEA. On the basis of another seven cases, collected from the literature, the MEA syndrome of mixed type is reviewed with special reference to the phylogenetic origin of the cells of the APUD system. | Multiple endocrine adenomatosis of mixed type. A case of multiple endocrine adenomatosis (MEA) of mixed type is presented. The syndrome, observed in a 65 year-old female, consisted of multiple neurofibroadenomatosis, medullary thyroid carcinoma, multiple adenomata of the parathyroids, adrenal cortical adenoma and small cell anaplastic bronchogenic carcinoma. Thus, it was composed of type 1 as well as of type 2 MEA. On the basis of another seven cases, collected from the literature, the MEA syndrome of mixed type is reviewed with special reference to the phylogenetic origin of the cells of the APUD system. | [
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PMID:10720 | Current dimensions of the endocrine system. | The basic and clinical sciences have become fused in the investigation of relatively new syndromes and their pathogenesis. The measurement of hormone content in serum and tissues and the elucidation of its biologic effect via the membrane and cytoplasmic receptors leads to diagnostic and prognostic accuracy. New breakthrough advances in clinical and cellular phenomena will portend new horizons for more specific diagnoses and modern treatment of present and new endocrinopathies. The dimensions of the neuroendocrine system are expanding; the future perimeters are beyond sight today. | Current dimensions of the endocrine system. The basic and clinical sciences have become fused in the investigation of relatively new syndromes and their pathogenesis. The measurement of hormone content in serum and tissues and the elucidation of its biologic effect via the membrane and cytoplasmic receptors leads to diagnostic and prognostic accuracy. New breakthrough advances in clinical and cellular phenomena will portend new horizons for more specific diagnoses and modern treatment of present and new endocrinopathies. The dimensions of the neuroendocrine system are expanding; the future perimeters are beyond sight today. | [
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PMID:10722 | Present state of alpha- and beta-adrenergic drugs I. The adrenergic receptor. | The cardiovascular alpha adrenergic receptors evoke vasoconstriction, the cardiovascular beta receptors evoke vasodilation and cardiac stimulation. All blood vessels have both alpha and beta receptors. In some areas, for example skin and kidney, the alpha receptors predominate. In some vascular beds, for example the nutrient vessels in skeletal muscle, beta receptors predominate. In other beds, such as coronary, visceral, and connective tissue both receptors are active. The cardiovascular effects of adrenergic agonists depend on which receptor they act on. Phenylephrine is specific for alpha receptors. Isoproterenol is specific for beta receptors. Epinephrine and norepinephrine act on both. The real value of knowing the receptor specificity of each agonist is that side effects can more easily be predicted. For example, adrenergic cardiac stimulants are antiasthmatics. Therefore, adrenergic antiasthmatics can produce excessive cardiac stimulation. For the future, agonists that are not only receptor-specific but also tissue-specific will be developed. The first of these in the United States is terbutaline. The rest of the world has in addition a similar drug, salbutamol. No one knows if this drug will be approved for use by American physicians. | Present state of alpha- and beta-adrenergic drugs I. The adrenergic receptor. The cardiovascular alpha adrenergic receptors evoke vasoconstriction, the cardiovascular beta receptors evoke vasodilation and cardiac stimulation. All blood vessels have both alpha and beta receptors. In some areas, for example skin and kidney, the alpha receptors predominate. In some vascular beds, for example the nutrient vessels in skeletal muscle, beta receptors predominate. In other beds, such as coronary, visceral, and connective tissue both receptors are active. The cardiovascular effects of adrenergic agonists depend on which receptor they act on. Phenylephrine is specific for alpha receptors. Isoproterenol is specific for beta receptors. Epinephrine and norepinephrine act on both. The real value of knowing the receptor specificity of each agonist is that side effects can more easily be predicted. For example, adrenergic cardiac stimulants are antiasthmatics. Therefore, adrenergic antiasthmatics can produce excessive cardiac stimulation. For the future, agonists that are not only receptor-specific but also tissue-specific will be developed. The first of these in the United States is terbutaline. The rest of the world has in addition a similar drug, salbutamol. No one knows if this drug will be approved for use by American physicians. | [
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PMID:10724 | Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts. | The residual hexosaminidase isoenzymes in juvenile Sandhoff and infantile Sandhoff disease fibroblasts, have been determined by starch gel electrophoresis and column isoelectric focusing. Hex A and hex S are the major residual isozymes in fibroblasts from the juvenile patient, while hex B is barely detectable. Only hex S could be detected in fibroblasts from infantile Sandhoff patients. These results suggest that the defects in juvenile and infantile Sandhoff disease may be different allelic modifications of the beta subunit common to hex A and hex B. | Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts. The residual hexosaminidase isoenzymes in juvenile Sandhoff and infantile Sandhoff disease fibroblasts, have been determined by starch gel electrophoresis and column isoelectric focusing. Hex A and hex S are the major residual isozymes in fibroblasts from the juvenile patient, while hex B is barely detectable. Only hex S could be detected in fibroblasts from infantile Sandhoff patients. These results suggest that the defects in juvenile and infantile Sandhoff disease may be different allelic modifications of the beta subunit common to hex A and hex B. | [
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PMID:10725 | Effect of sodium depletion on plasma renin concentration before and during adrenergic beta-receptor blockade with propranolol in normotensive man. | Plasma renin levels have been used to discriminate between different forms of hypertension, but how to define the normal range of plasma renin levels has not been agreed upon. Sodium depletion stimulates renin release. Evaluation of plasma renin would, therefore seem possible only in relation to sodium balance. Plasma renin concentration and concurrent daily sodium excretion were determined in 33 healthy normotensive subjects (control group) ingesting high, normal and low sodium diets. A well-defined hyperbolic relationship was found between the two variables indicating that the physiologic level of plasma renin concentration depends on the state of sodium balance. An increase in plasma potassium concentration may reduce plasma renin concentration, but this appeared to be overruled by the stimulating effect of sodium depletion. To examine whether beta-adrenergic stimulation contributes to the increase in plasma renin concentration during sodium depletion, the relationship between plasma renin concentration and concurrent sodium excretion was studied during beta-receptor blockade with propranolol. In 20 healthy normotensive subjects in whom beta-receptor blockade was verified by a significant reduction in pulse rate, the same hyperbolic relationship was found between plasma renin concentration and sodium excretion as in the control group showing that sodium depletion stimulates renin release independent of sympathetic nervous activity. | Effect of sodium depletion on plasma renin concentration before and during adrenergic beta-receptor blockade with propranolol in normotensive man. Plasma renin levels have been used to discriminate between different forms of hypertension, but how to define the normal range of plasma renin levels has not been agreed upon. Sodium depletion stimulates renin release. Evaluation of plasma renin would, therefore seem possible only in relation to sodium balance. Plasma renin concentration and concurrent daily sodium excretion were determined in 33 healthy normotensive subjects (control group) ingesting high, normal and low sodium diets. A well-defined hyperbolic relationship was found between the two variables indicating that the physiologic level of plasma renin concentration depends on the state of sodium balance. An increase in plasma potassium concentration may reduce plasma renin concentration, but this appeared to be overruled by the stimulating effect of sodium depletion. To examine whether beta-adrenergic stimulation contributes to the increase in plasma renin concentration during sodium depletion, the relationship between plasma renin concentration and concurrent sodium excretion was studied during beta-receptor blockade with propranolol. In 20 healthy normotensive subjects in whom beta-receptor blockade was verified by a significant reduction in pulse rate, the same hyperbolic relationship was found between plasma renin concentration and sodium excretion as in the control group showing that sodium depletion stimulates renin release independent of sympathetic nervous activity. | [
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PMID:10721 | [Etiopathogenesis of necrotizing arteritis (leukocytoclastic vasculitis)]. | The small vessel's necrotizing angiitis (necrotizing microangiitis (NMA), leucocytoclastic angiitis) form a continuous spectrum from the exclusively cutaneous forms of Gougreot, to those which seriously affect the viscera, as the very acute and fatal cases of Zeek, passing through a series of intermediate phases, in which Schönlein-Henoch's purpura is found. In all of these clinical forms, the existence of an allergic mechanism has been suggested from their origin itself and in 1964 Alarcón-Segovia and Brown grouped them under the common denominator of allergic angiitis. Later investigations are far from completely confirming this hypothesis. In isolated cases, the clinical sequence corroborates the hypothesis of a bacterian aetiology (local septic focus), but in the Schónlein-Henoch purpura it has not been proven that there is a greater streptococcus beta-haemolytic frequency is the throat nor a greater number of antibodies in the serum than in normal children or those affected by illnesses not related to rheumatic fever. The aetiologic role of drugs and food is very difficult to prove. The anatomopathologic similarity between the Arthus reaction, the serum sickness and the spontaneous human NMA have led to the hypothesis that the NMA are immunocomplex (IC) diseases. In order to try to prove this, basically three techniques have been used: Direct immunofluorescence to show the IC tissue deposits, and mixed cryoglobulinemia and the serum's anti-complementary activity for the circulating IC. Direct immunofluorescence shows, in approximately 50% of the cases, the presence of IgG and C3 in the damaged vessels (also IgM with frequency). But, are these found combined as complexes? Parish, in some cases of presumably post-bacterial angiitis, has shown the simultaneous presence of the bacterian antigen and the Ig. The direct immunofluorescence negativity can be due to: (1) The IC being rapidly eliminated by the neutrophils; (2) the fact that these are nonimmunologic pathologic cases. On the other hand, the IC deposit could be a passive phenomenon in a previously damaged vessel. With great frequency, mixed cryoglobulinemia is associated with systemic conditions of the auto-immune type (collagenosis, etc) or of the malignant lymphoid haemopathy type, and with NMA. With what frequency is mixed cryoglobulinemia found in the NMA? 33% of the 47 cream's cases. What is the pathogenic relationship between processes? Often the cryoglobulin components are found deposited in angiitis lesions, but its presence and intensity does not guard any relationship with the cryoglobulinemia rate. Besides the 33% of the cases with mixed cryoglobulinemia, 13% serum's anti-complementary activity, and the remaining 54% had no indications of circulating IC with the usual techniques. Of 104 cases of Schónlein-Henoch purpura, 75 of which had nephritis, only 10% had hypocomplementemia. In summary, in about 50% of the patients with NMA, no reasonable indication of IC disease was found... | [Etiopathogenesis of necrotizing arteritis (leukocytoclastic vasculitis)]. The small vessel's necrotizing angiitis (necrotizing microangiitis (NMA), leucocytoclastic angiitis) form a continuous spectrum from the exclusively cutaneous forms of Gougreot, to those which seriously affect the viscera, as the very acute and fatal cases of Zeek, passing through a series of intermediate phases, in which Schönlein-Henoch's purpura is found. In all of these clinical forms, the existence of an allergic mechanism has been suggested from their origin itself and in 1964 Alarcón-Segovia and Brown grouped them under the common denominator of allergic angiitis. Later investigations are far from completely confirming this hypothesis. In isolated cases, the clinical sequence corroborates the hypothesis of a bacterian aetiology (local septic focus), but in the Schónlein-Henoch purpura it has not been proven that there is a greater streptococcus beta-haemolytic frequency is the throat nor a greater number of antibodies in the serum than in normal children or those affected by illnesses not related to rheumatic fever. The aetiologic role of drugs and food is very difficult to prove. The anatomopathologic similarity between the Arthus reaction, the serum sickness and the spontaneous human NMA have led to the hypothesis that the NMA are immunocomplex (IC) diseases. In order to try to prove this, basically three techniques have been used: Direct immunofluorescence to show the IC tissue deposits, and mixed cryoglobulinemia and the serum's anti-complementary activity for the circulating IC. Direct immunofluorescence shows, in approximately 50% of the cases, the presence of IgG and C3 in the damaged vessels (also IgM with frequency). But, are these found combined as complexes? Parish, in some cases of presumably post-bacterial angiitis, has shown the simultaneous presence of the bacterian antigen and the Ig. The direct immunofluorescence negativity can be due to: (1) The IC being rapidly eliminated by the neutrophils; (2) the fact that these are nonimmunologic pathologic cases. On the other hand, the IC deposit could be a passive phenomenon in a previously damaged vessel. With great frequency, mixed cryoglobulinemia is associated with systemic conditions of the auto-immune type (collagenosis, etc) or of the malignant lymphoid haemopathy type, and with NMA. With what frequency is mixed cryoglobulinemia found in the NMA? 33% of the 47 cream's cases. What is the pathogenic relationship between processes? Often the cryoglobulin components are found deposited in angiitis lesions, but its presence and intensity does not guard any relationship with the cryoglobulinemia rate. Besides the 33% of the cases with mixed cryoglobulinemia, 13% serum's anti-complementary activity, and the remaining 54% had no indications of circulating IC with the usual techniques. Of 104 cases of Schónlein-Henoch purpura, 75 of which had nephritis, only 10% had hypocomplementemia. In summary, in about 50% of the patients with NMA, no reasonable indication of IC disease was found... | [
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PMID:10727 | Methodologic problems in plasma renin activity measurements. | The influence of pH and angiotensinase inhibitors on the in vitro generation of angiotensin I during PRA measurements has been investigated. PRA values obtained at pH 5.7 are higher than those obtained at pH 7.4. At pH 5.7, values obtained using diisopropylfluorophosphate (DRP 9 mM) as an angiotensinase inhibitor are higher than values obtained with a mixture of dimercaprol (BAL, 1.6 mM) and hydroxyquinoline (8-OHQ, 3 to 4 mM). Since the two methods for inhibiting angiotensinase are completely and equally efficient, it is suggested that these inhibitors might interfere with the renin angiotensinogen reaction. Significant correlations are observed between the PRA values obtained by the different methods which have been studied. Using an incubation pH of 5.7, and BAL and 8-OH quinoline as angiotensinase inhibitors, the distribution of PRA values in a population of 124 hospitalized hypertensive patients ingesting a normal sodium diet had been studied, and it has been demonstrated that the sensitivity of this method of measurement can detect small changes in PRA in patients with low renin activity. | Methodologic problems in plasma renin activity measurements. The influence of pH and angiotensinase inhibitors on the in vitro generation of angiotensin I during PRA measurements has been investigated. PRA values obtained at pH 5.7 are higher than those obtained at pH 7.4. At pH 5.7, values obtained using diisopropylfluorophosphate (DRP 9 mM) as an angiotensinase inhibitor are higher than values obtained with a mixture of dimercaprol (BAL, 1.6 mM) and hydroxyquinoline (8-OHQ, 3 to 4 mM). Since the two methods for inhibiting angiotensinase are completely and equally efficient, it is suggested that these inhibitors might interfere with the renin angiotensinogen reaction. Significant correlations are observed between the PRA values obtained by the different methods which have been studied. Using an incubation pH of 5.7, and BAL and 8-OH quinoline as angiotensinase inhibitors, the distribution of PRA values in a population of 124 hospitalized hypertensive patients ingesting a normal sodium diet had been studied, and it has been demonstrated that the sensitivity of this method of measurement can detect small changes in PRA in patients with low renin activity. | [
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PMID:10728 | Plasma prorenin: cryoactivation and relationship to renin substrate in normal subjects. | We previously demonstrated an inactive form of renin, termed prorenin, in the plasma of normal, hypertensive and anephric patients. Prorenin activity can be determined in plasma from the total renin activity after activation, minus the prior endogenous plasma renin activity. In the present study, conditions for cryoactivation of prorenin have been defined. Plasma prorenin is slowly converted to active renin-like material at -5 degrees C at pH 7.4. Activation takes four days and does not occur at pH 5.0. The degree of activation increases above pH 5 and is greatest between pH 7 and pH 9. Thus, almost no cryoactivation of prorenin occurs at the pH optimum for renin (5.7) in contrast to maximum activation at pH 7.4. No activation has been observed in the frozen state, but it does occur with decreasing rapidity at temperatures from -5 degress to +4 degress C. Since blood samples obtained for the determination of plasma renin activity are routinely chilled upon collection by most laboratories, some activatin of prorenin most likely occurs in all routine renin assays. The pH optimum of the enzymatic reaction of the activated prorenin in plasma is 5.8, the same as for renal renin, and the shape of the pH optimum curve is similar to that of renal renin added to human plasma. In a group of 23 normal subjects with plasma renin activity of 3.5 +/- 2.9 (SD), the activated prorenin increment was found to be significantly higher, 6.3 +/- 5.0 (SD) ng/ml/hour. Unlike plasma renin activity, prorenin activity in these normal subjects was directly related to the concentration of renin substrate (p less than 0.001). When the actual "concentration" of prorenin was calculated using renal renin as the reference standard, a direct relationship was also found between the concentration of prorenin and renin substrate (p less than 0.01). The observed relationship between prorenin and renin substrate concentrations might be a consequence of their regulation by common factors. | Plasma prorenin: cryoactivation and relationship to renin substrate in normal subjects. We previously demonstrated an inactive form of renin, termed prorenin, in the plasma of normal, hypertensive and anephric patients. Prorenin activity can be determined in plasma from the total renin activity after activation, minus the prior endogenous plasma renin activity. In the present study, conditions for cryoactivation of prorenin have been defined. Plasma prorenin is slowly converted to active renin-like material at -5 degrees C at pH 7.4. Activation takes four days and does not occur at pH 5.0. The degree of activation increases above pH 5 and is greatest between pH 7 and pH 9. Thus, almost no cryoactivation of prorenin occurs at the pH optimum for renin (5.7) in contrast to maximum activation at pH 7.4. No activation has been observed in the frozen state, but it does occur with decreasing rapidity at temperatures from -5 degress to +4 degress C. Since blood samples obtained for the determination of plasma renin activity are routinely chilled upon collection by most laboratories, some activatin of prorenin most likely occurs in all routine renin assays. The pH optimum of the enzymatic reaction of the activated prorenin in plasma is 5.8, the same as for renal renin, and the shape of the pH optimum curve is similar to that of renal renin added to human plasma. In a group of 23 normal subjects with plasma renin activity of 3.5 +/- 2.9 (SD), the activated prorenin increment was found to be significantly higher, 6.3 +/- 5.0 (SD) ng/ml/hour. Unlike plasma renin activity, prorenin activity in these normal subjects was directly related to the concentration of renin substrate (p less than 0.001). When the actual "concentration" of prorenin was calculated using renal renin as the reference standard, a direct relationship was also found between the concentration of prorenin and renin substrate (p less than 0.01). The observed relationship between prorenin and renin substrate concentrations might be a consequence of their regulation by common factors. | [
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PMID:10729 | Beta-adrenergic receptor blocking drugs in spontaneous hypertension. | Eleven beta-adrenergic receptor blocking agents and derivatives were evaluated for their ability to affect systolic arterial blood pressure and pulse rate in unanesthetized, male spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto (WKY) controls. Animals ranged from 7 to 76 weeks of age. The subcutaneous injection of 5 and 45 mg/kg metoprolol in 52 to 64 week old SHRs and 45 mg/kg twice a day to 26 to 29 week old SHRs produced a significant decrease in blooc pressure. The subcutaneous injection of pindolol (0.1 and 1.0 mg/kg) produced a greater and more consistent depressor effect in mature SHRs. The subcutaneous administration of sotalol (100 mg/kg) and alprenolol (20 mg/kg) resulted in a depressor action which was significant 120 minutes after injection of the drug. In the doses used, propranolol, oxprenolol, 4-hydroxypropranolol and K9-1366 produced pressor effect in SHRs. Propranolol did not cause this pressor effect in prehypertensive (seven week old) SHRs. Practolol, dextro-propranolol and KO-1313 had no effect on blood pressure in the doses used. Propranolol, pindolol, metoprolol, dextro-propranolol, 4-hydroxypropranolol, practolol, oxprenolol, KO-1366 and KO-1313 produced no significant effects on blood pressure in normotensive WKY controls in the doses tested. Placing oral doses of 160 mg/kg/day of metoprolol in the drinking water for seven days significantly lowered blood pressure in 14 week old SHRs previously exposed to ineffective doses of 77 mg/kg/day for 24 days. The administration of oral doses of oxprenolol (40 mg/kg/day) in drinking water for three weeks had a slight but insignificant pressor effect. Smaller doses of metoprolol (15 and 39 mg/kg/day for three to four weeks) and practolol (70 to 85 mg/kg/day for two weeks) had no effect on 52 week old SHRs. Oral doses of pindolol, metoprolol, practolol and oxprenolol had no significant effect on blood pressure in WKY controls. There was no clear relationship between the effects of the drugs on blood pressure and their ability to affect the pulse rate. Similarly, there did not appear to be any consistent relationship between the potency of the beta-blocking drug and the blood pressure lowering action. In addition, neither cardioselective beta-blockade nor sympathomimetic properties allowed the prediction of blood pressure responses to the administration of those agents possessing these features. Although SHRs provide a valuable model of human essential hypertension, the variable effects reported here and elsewhere in the literature require caution as to the applicability and usefulness of testing and evaluating beta-adrenergic blocking drugs for theri potential anti-hypertensive effects in this particular form of experimental hypertension. | Beta-adrenergic receptor blocking drugs in spontaneous hypertension. Eleven beta-adrenergic receptor blocking agents and derivatives were evaluated for their ability to affect systolic arterial blood pressure and pulse rate in unanesthetized, male spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto (WKY) controls. Animals ranged from 7 to 76 weeks of age. The subcutaneous injection of 5 and 45 mg/kg metoprolol in 52 to 64 week old SHRs and 45 mg/kg twice a day to 26 to 29 week old SHRs produced a significant decrease in blooc pressure. The subcutaneous injection of pindolol (0.1 and 1.0 mg/kg) produced a greater and more consistent depressor effect in mature SHRs. The subcutaneous administration of sotalol (100 mg/kg) and alprenolol (20 mg/kg) resulted in a depressor action which was significant 120 minutes after injection of the drug. In the doses used, propranolol, oxprenolol, 4-hydroxypropranolol and K9-1366 produced pressor effect in SHRs. Propranolol did not cause this pressor effect in prehypertensive (seven week old) SHRs. Practolol, dextro-propranolol and KO-1313 had no effect on blood pressure in the doses used. Propranolol, pindolol, metoprolol, dextro-propranolol, 4-hydroxypropranolol, practolol, oxprenolol, KO-1366 and KO-1313 produced no significant effects on blood pressure in normotensive WKY controls in the doses tested. Placing oral doses of 160 mg/kg/day of metoprolol in the drinking water for seven days significantly lowered blood pressure in 14 week old SHRs previously exposed to ineffective doses of 77 mg/kg/day for 24 days. The administration of oral doses of oxprenolol (40 mg/kg/day) in drinking water for three weeks had a slight but insignificant pressor effect. Smaller doses of metoprolol (15 and 39 mg/kg/day for three to four weeks) and practolol (70 to 85 mg/kg/day for two weeks) had no effect on 52 week old SHRs. Oral doses of pindolol, metoprolol, practolol and oxprenolol had no significant effect on blood pressure in WKY controls. There was no clear relationship between the effects of the drugs on blood pressure and their ability to affect the pulse rate. Similarly, there did not appear to be any consistent relationship between the potency of the beta-blocking drug and the blood pressure lowering action. In addition, neither cardioselective beta-blockade nor sympathomimetic properties allowed the prediction of blood pressure responses to the administration of those agents possessing these features. Although SHRs provide a valuable model of human essential hypertension, the variable effects reported here and elsewhere in the literature require caution as to the applicability and usefulness of testing and evaluating beta-adrenergic blocking drugs for theri potential anti-hypertensive effects in this particular form of experimental hypertension. | [
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PMID:10730 | Modern system for treating high blood pressure based on renin profiling and vasoconstriction-volume analysis: a primary role for beta blocking drugs such as propranolol. | A new system is proposed for treating the spectrum of patients with high blood pressure. It is based on studies of the renin axis using renin profiling, pharmacologic probes and our bipolar vasoconstriction-volume hypothesis. The new system does not require renin profiling, pharmacologic testing or a vasoconstriction-volume analysis for widespread application. But these procedures, whenever available, will make treatment more efficient and more certain, and at the same time provide better base line definition. In the new system, all patients, except the elderly and those with congestive heart failure, bradycardia or a history of asthma, are treated first with propranolol alone, a procedure which will diminish or normalize blood pressure in many patients with high and noraml renin levels. For nonresponders, diuretic therapy is then superimposed. Subsequently, a propranolol subtraction trial picks out the low-renin patients who will usually respond to a diuretic alone. This program is likely to be fully effective in possible up to 85 per cent of patients. For the residual smaller fraction, drugs such as hydralazine, methyl DOPA, clonidine, reserpine or guanethidine are then added in traditional trial and error fashion. The proposed system has the theoretic attraction for long-term commitment, implicit in antihypertensive therapy, of achieving blood pressure control in large fractions with one drug instead of two or with two drugs instead of three or more. Moreover, the large groups who respond to therapy with propranolol alone (most high-renin and normal-renin patients) or to diuretics alone (most low-renin patients) gain the advantage of simple, more specific, long-term (i.e., antirenin or antivolume) therapy. The use of propranolol alone has practical and theoretic advantages over diuretics. Control may be achieved with even fewer side effects and without hypokalemia and chronic dehydration with its possibly adverse consequences (hyperuricemia, azotemia, hyperlipidemia, hyperreninemia, increased blood viscosity). Also, propranolol provides more direct control of the increased peripheral resistance and of neurogenically-induced swings in blood pressure. At the same time, the new system efficiently exploits the long-term use of diuretic therapy alone in low-renin patients in whom volume excess seems a causal factor. And it tends to avoid the use of diuretics in high-renin patients and of beta-blockers in low-renin patients in whom these drug types may be contraindicated. | Modern system for treating high blood pressure based on renin profiling and vasoconstriction-volume analysis: a primary role for beta blocking drugs such as propranolol. A new system is proposed for treating the spectrum of patients with high blood pressure. It is based on studies of the renin axis using renin profiling, pharmacologic probes and our bipolar vasoconstriction-volume hypothesis. The new system does not require renin profiling, pharmacologic testing or a vasoconstriction-volume analysis for widespread application. But these procedures, whenever available, will make treatment more efficient and more certain, and at the same time provide better base line definition. In the new system, all patients, except the elderly and those with congestive heart failure, bradycardia or a history of asthma, are treated first with propranolol alone, a procedure which will diminish or normalize blood pressure in many patients with high and noraml renin levels. For nonresponders, diuretic therapy is then superimposed. Subsequently, a propranolol subtraction trial picks out the low-renin patients who will usually respond to a diuretic alone. This program is likely to be fully effective in possible up to 85 per cent of patients. For the residual smaller fraction, drugs such as hydralazine, methyl DOPA, clonidine, reserpine or guanethidine are then added in traditional trial and error fashion. The proposed system has the theoretic attraction for long-term commitment, implicit in antihypertensive therapy, of achieving blood pressure control in large fractions with one drug instead of two or with two drugs instead of three or more. Moreover, the large groups who respond to therapy with propranolol alone (most high-renin and normal-renin patients) or to diuretics alone (most low-renin patients) gain the advantage of simple, more specific, long-term (i.e., antirenin or antivolume) therapy. The use of propranolol alone has practical and theoretic advantages over diuretics. Control may be achieved with even fewer side effects and without hypokalemia and chronic dehydration with its possibly adverse consequences (hyperuricemia, azotemia, hyperlipidemia, hyperreninemia, increased blood viscosity). Also, propranolol provides more direct control of the increased peripheral resistance and of neurogenically-induced swings in blood pressure. At the same time, the new system efficiently exploits the long-term use of diuretic therapy alone in low-renin patients in whom volume excess seems a causal factor. And it tends to avoid the use of diuretics in high-renin patients and of beta-blockers in low-renin patients in whom these drug types may be contraindicated. | [
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PMID:10731 | Controlled trial of fetal intensive care. | A fetal intensive care unit was formed at the Queen Victoria Memorial Hospital in 1972. Because of some doubt concerning the value of fetal intensive care, a controlled clinical trial including all high-risk patients was performed. The trial clearly showed that intensive care is associated with improved neurologic and biochemical status of the neonate; however, it is possible that this improvement results from the use of fetal diagnostic tests or some other factor associated with intensive care. Sufficient evidence was gathered to warrant the continuation of fetal intensive care in this hospital, but in other contries, where funding is difficult to obtain, a controlled trial would appear justified. | Controlled trial of fetal intensive care. A fetal intensive care unit was formed at the Queen Victoria Memorial Hospital in 1972. Because of some doubt concerning the value of fetal intensive care, a controlled clinical trial including all high-risk patients was performed. The trial clearly showed that intensive care is associated with improved neurologic and biochemical status of the neonate; however, it is possible that this improvement results from the use of fetal diagnostic tests or some other factor associated with intensive care. Sufficient evidence was gathered to warrant the continuation of fetal intensive care in this hospital, but in other contries, where funding is difficult to obtain, a controlled trial would appear justified. | [
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PMID:10732 | Other hydrophilic lens environments: pH. | Although hydrophilic contact lenses are specifically designed for compatibility with the eye environment, i.e., the tears, they will, with the exception of continuous wear types, spend a significant fraction of their daily cycle in other solutions. This investigation explores the pH characteristics of certain of those alternative media. | Other hydrophilic lens environments: pH. Although hydrophilic contact lenses are specifically designed for compatibility with the eye environment, i.e., the tears, they will, with the exception of continuous wear types, spend a significant fraction of their daily cycle in other solutions. This investigation explores the pH characteristics of certain of those alternative media. | [
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PMID:10733 | Participation of H1 and H2 histamine receptors in physiological vasodilator responses. | Histamine causes vasodilation in the dog by activation of H1 and H2 receptors blocked by mepyramine and metiamide, respectively. Experiments were conducted in anesthetized dogs to determine the participation of H1 and H2 receptors in several forms of physiological dilatation. Mepyramine attenuated both histamine-induced and active-reflex dilatation in the hindlimb. Metiamide caused a further reduction in both sets of dilatation. Neither single nor combined antihistamines reduced dilatation due to exercise or after temporary occlusion of the circulation in the hindlimb. Poststimulation dilatation in the gracilis muscle was partially attenuated by metiamide or mepyramine. Neither dilatation caused by sympathetic nerve stimulation in the hindpaw nor dilatation in the gracilis muscle caused by compound 48/80 was reduced by mepyramine. Following combined H1- and H2-receptor blockade, portions of both types of dilatation were reduced. These data provide evidence for the participation of both types of histamine receptor in active reflex dilatation, low-frequency neurogenic dilatation, dilatation caused by compound 48/80, and poststimulation dilatation. Neither type of histamine receptor appears to be involved in reactive hyperemia or dilatation caused by exercise. | Participation of H1 and H2 histamine receptors in physiological vasodilator responses. Histamine causes vasodilation in the dog by activation of H1 and H2 receptors blocked by mepyramine and metiamide, respectively. Experiments were conducted in anesthetized dogs to determine the participation of H1 and H2 receptors in several forms of physiological dilatation. Mepyramine attenuated both histamine-induced and active-reflex dilatation in the hindlimb. Metiamide caused a further reduction in both sets of dilatation. Neither single nor combined antihistamines reduced dilatation due to exercise or after temporary occlusion of the circulation in the hindlimb. Poststimulation dilatation in the gracilis muscle was partially attenuated by metiamide or mepyramine. Neither dilatation caused by sympathetic nerve stimulation in the hindpaw nor dilatation in the gracilis muscle caused by compound 48/80 was reduced by mepyramine. Following combined H1- and H2-receptor blockade, portions of both types of dilatation were reduced. These data provide evidence for the participation of both types of histamine receptor in active reflex dilatation, low-frequency neurogenic dilatation, dilatation caused by compound 48/80, and poststimulation dilatation. Neither type of histamine receptor appears to be involved in reactive hyperemia or dilatation caused by exercise. | [
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PMID:10734 | Maleate-induced bicarbonaturia in the dog: a carbonic anhydrase-independene effect. | Studies were performed to characterize the renal effects of maleate in anesthetized dogs. Following the intravenous administration of maleate or maleic acid (50 mg/kg), mean fractional bicarbonate excretion (CHCO3/GFR) rose to as high as 26%. Na, K, and phosphate excretion also increased markedly, whereas C1 excretion remained low. An initial transient fall in urinary pH from 6.53 to 6.13 contrasted sharply with the rapid alkalinization of the urine induced by acetazolamide administration. During saline expansion CHCO3/GFR rose from 4 to 37% after maleate administration, whereas Cl excretion did not change significantly. During continuous carbonic anhydrase inhibition with acetazolamide, maleate administration resulted in a further rise in CHCO3/GFR from 22 to 35%. Whereas CPO4/GFR increased only from 1 to 3% during acetazolamide administration, this ratio reached 75% following the addition of maleate. Fumarate, the transisomer of maleate, and malonate, a well-known inhibitor of Krebs cycle, failed to affect bicarbonate excretion. This study demonstrates that maleate inhibits the fraction of bicarbonate reabsorption uncatalyzed by carbonic anhydrase. Impaired anionic reabsorption of bicarbonate or accelerated passive backflux of this ion into proximal tubular lumen are the two mechanisms that best explain the bicarbonaturia induced by maleate. | Maleate-induced bicarbonaturia in the dog: a carbonic anhydrase-independene effect. Studies were performed to characterize the renal effects of maleate in anesthetized dogs. Following the intravenous administration of maleate or maleic acid (50 mg/kg), mean fractional bicarbonate excretion (CHCO3/GFR) rose to as high as 26%. Na, K, and phosphate excretion also increased markedly, whereas C1 excretion remained low. An initial transient fall in urinary pH from 6.53 to 6.13 contrasted sharply with the rapid alkalinization of the urine induced by acetazolamide administration. During saline expansion CHCO3/GFR rose from 4 to 37% after maleate administration, whereas Cl excretion did not change significantly. During continuous carbonic anhydrase inhibition with acetazolamide, maleate administration resulted in a further rise in CHCO3/GFR from 22 to 35%. Whereas CPO4/GFR increased only from 1 to 3% during acetazolamide administration, this ratio reached 75% following the addition of maleate. Fumarate, the transisomer of maleate, and malonate, a well-known inhibitor of Krebs cycle, failed to affect bicarbonate excretion. This study demonstrates that maleate inhibits the fraction of bicarbonate reabsorption uncatalyzed by carbonic anhydrase. Impaired anionic reabsorption of bicarbonate or accelerated passive backflux of this ion into proximal tubular lumen are the two mechanisms that best explain the bicarbonaturia induced by maleate. | [
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PMID:10735 | Tetanic hyperpolarization of single medullated nerve fibers in sodium and lithium. | Repetitive stimulation of a single medullated nerve fiber of Xenopus yields a succession of postspike voltage-time curves which are nearly coincident until attainment of a voltage that corresponds to that of the maximum attained by the normal postspike undershoot. Initially the interspike potential returns toward a resting level after this brief phase of hyperpolarization. However, as tetanization proceeds, a pattern of hyperpolarization develops with the result that, in the tetanic steady state, there exists a progressive hyperpolarization throughout each interspike interval. Extent of postspike hyperpolarization in terms of a deviation deltaVm from the resting level of membrane potential is approximated by the variation deltaVm = delta[MNa + MK]/[GNa + GK] where MNa and MK are current densities associated with active pumping of sodium and potassium ions and GNa and GK are corresponding time-dependent leak conductances. Tetanic hyperpolarization is reversibly abolished by cyanide and by exposure to lithium Ringer. Eventual reappearance of tetanic hyperpolarization in the presence of lithium Ringer suggests lithium pumping. | Tetanic hyperpolarization of single medullated nerve fibers in sodium and lithium. Repetitive stimulation of a single medullated nerve fiber of Xenopus yields a succession of postspike voltage-time curves which are nearly coincident until attainment of a voltage that corresponds to that of the maximum attained by the normal postspike undershoot. Initially the interspike potential returns toward a resting level after this brief phase of hyperpolarization. However, as tetanization proceeds, a pattern of hyperpolarization develops with the result that, in the tetanic steady state, there exists a progressive hyperpolarization throughout each interspike interval. Extent of postspike hyperpolarization in terms of a deviation deltaVm from the resting level of membrane potential is approximated by the variation deltaVm = delta[MNa + MK]/[GNa + GK] where MNa and MK are current densities associated with active pumping of sodium and potassium ions and GNa and GK are corresponding time-dependent leak conductances. Tetanic hyperpolarization is reversibly abolished by cyanide and by exposure to lithium Ringer. Eventual reappearance of tetanic hyperpolarization in the presence of lithium Ringer suggests lithium pumping. | [
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PMID:10736 | Glutamine synthetase and glutamyltransferase in the kidney of man, dog, and rat. | Glutamine synthetase (GS) is known to exist in the kidney of the rat, guinea pig, rabbit, and sheep but not in that of the dog, pig, cat, or pigeon. No data is available in man. Assay of histologically normal renal tissue obtained in human subjects during surgery for abdominal vascular disease failed to demonstrate significant GS activity. In addition, L-glutamine gamma-glutamyltransferase (GT) activity was also very low. The same results were observed in the dog, in which both GS and GT activities did not exceed 15% of those found in the kidney of the normal rat. In the latter animal both GS and GT activities are higher in the outer medulla (312 and 1,165 mumol/h per g wet wt, respectively) than in the cortex (230 and 844, respectively). During metabolic acidosis, GT activity did not change but GS activity decreased in the outer medulla by 40%. When renal cortex slices from normal rats were incubated in the presence of ammonia, glutamate, and octanoate (as a source of ATP), net synthesis of glutamine was readily demonstrated in contrast to slices from normal DOGS. The present studies demonstrate that the kidney of man, like that of the dog, is devoid of significant glutamine synthetase and glutamine gamma-glutamyltransferase activities. In the rat, we have confirmed the functional significance of GS activity in the kidney. We have also shown that renal GT activity is ammoniagenic in vitro in this animal, but the contribution of this system to total ammonia production in vivo remains to be demonstrated. | Glutamine synthetase and glutamyltransferase in the kidney of man, dog, and rat. Glutamine synthetase (GS) is known to exist in the kidney of the rat, guinea pig, rabbit, and sheep but not in that of the dog, pig, cat, or pigeon. No data is available in man. Assay of histologically normal renal tissue obtained in human subjects during surgery for abdominal vascular disease failed to demonstrate significant GS activity. In addition, L-glutamine gamma-glutamyltransferase (GT) activity was also very low. The same results were observed in the dog, in which both GS and GT activities did not exceed 15% of those found in the kidney of the normal rat. In the latter animal both GS and GT activities are higher in the outer medulla (312 and 1,165 mumol/h per g wet wt, respectively) than in the cortex (230 and 844, respectively). During metabolic acidosis, GT activity did not change but GS activity decreased in the outer medulla by 40%. When renal cortex slices from normal rats were incubated in the presence of ammonia, glutamate, and octanoate (as a source of ATP), net synthesis of glutamine was readily demonstrated in contrast to slices from normal DOGS. The present studies demonstrate that the kidney of man, like that of the dog, is devoid of significant glutamine synthetase and glutamine gamma-glutamyltransferase activities. In the rat, we have confirmed the functional significance of GS activity in the kidney. We have also shown that renal GT activity is ammoniagenic in vitro in this animal, but the contribution of this system to total ammonia production in vivo remains to be demonstrated. | [
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PMID:10737 | Calcium uptake by subcellular fractions of human umbilical artery. | Two different mechanisms for the active accumulation of Ca2+ by subcellular fractions of human umbilical artery are described. One, located in the mitochondrial fraction, was induced by exogenous ATP or respiratory substrates (ADP and succinate) and was inhibited by azide. The other, located in the microsomal fraction, was induced by ATP and potentiated by oxalate, but not inhibited by azide. Increasing ATP concentrations up to 4-5 mM increased microsomal Ca2+ accumulation, whereas increasing ATP concentration above 2-3 mM caused inhibition of mitochondrial Ca2+ uptake. Although changing pH from 7.4 to 7.2 had no effect on mitochondrial Ca2+ accumulation, it doubled microsomal uptake. Neither adenosine 3',5'-monophosphate nor guanosine 3',5'-monophosphate in the presence or absence of protein kinase and kinase modulator affected Ca2+ uptake by or phosphorylation of the subcellular fractions. Partially purified protein kinases from umbilical and beef skeletal muscle contained a component(s) distinguishable from the kinase on the basis of its heat stability that enhanced ATP-induced Ca2+ uptake by mitochondrial fractions from the umbilical artery. It is suggested that alterations in Ca2+ sequestration induced by changes in ATP concentration and intracellular pH in mitochondrial and microsomal fractions, respectively, could play a role in the control of arterial patency and closure with changes in PO2. | Calcium uptake by subcellular fractions of human umbilical artery. Two different mechanisms for the active accumulation of Ca2+ by subcellular fractions of human umbilical artery are described. One, located in the mitochondrial fraction, was induced by exogenous ATP or respiratory substrates (ADP and succinate) and was inhibited by azide. The other, located in the microsomal fraction, was induced by ATP and potentiated by oxalate, but not inhibited by azide. Increasing ATP concentrations up to 4-5 mM increased microsomal Ca2+ accumulation, whereas increasing ATP concentration above 2-3 mM caused inhibition of mitochondrial Ca2+ uptake. Although changing pH from 7.4 to 7.2 had no effect on mitochondrial Ca2+ accumulation, it doubled microsomal uptake. Neither adenosine 3',5'-monophosphate nor guanosine 3',5'-monophosphate in the presence or absence of protein kinase and kinase modulator affected Ca2+ uptake by or phosphorylation of the subcellular fractions. Partially purified protein kinases from umbilical and beef skeletal muscle contained a component(s) distinguishable from the kinase on the basis of its heat stability that enhanced ATP-induced Ca2+ uptake by mitochondrial fractions from the umbilical artery. It is suggested that alterations in Ca2+ sequestration induced by changes in ATP concentration and intracellular pH in mitochondrial and microsomal fractions, respectively, could play a role in the control of arterial patency and closure with changes in PO2. | [
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PMID:10738 | Intrarenal blood flow distribution in the desert quail following salt loading. | The total-kidney glomerular filtration rate (GFR) falls when birds are salt loaded. This fall in GFR is caused by glomerular intermittency. The nephrons that stop filtering are small, surface nephrons without loops of Henle. Larger nephrons with loops of Henle in the deeper regions of the kidney continue to filter during salt loading. Microfil casts were made of the renal microvasculature of the desert quail, Lophortyx gambelii, in an attempt to determine at what points intrarenal blood flow is regulated to cause glomerular intermittency. Casts of the renal vasculature were made in quail that were hydrated and in quail that were salt loaded. The results indicate that the small, surface nephrons stop filtering during salt loading because of a vasoconstriction at the level of the afferent arterioles of these nephrons. At the same time, blood flow is maintained to the large nephrons with loops of Henle. Reducing GFR at the expenses of excreting wastes can be viewed as a mechanism to conserve body water during periods of water deprivation. | Intrarenal blood flow distribution in the desert quail following salt loading. The total-kidney glomerular filtration rate (GFR) falls when birds are salt loaded. This fall in GFR is caused by glomerular intermittency. The nephrons that stop filtering are small, surface nephrons without loops of Henle. Larger nephrons with loops of Henle in the deeper regions of the kidney continue to filter during salt loading. Microfil casts were made of the renal microvasculature of the desert quail, Lophortyx gambelii, in an attempt to determine at what points intrarenal blood flow is regulated to cause glomerular intermittency. Casts of the renal vasculature were made in quail that were hydrated and in quail that were salt loaded. The results indicate that the small, surface nephrons stop filtering during salt loading because of a vasoconstriction at the level of the afferent arterioles of these nephrons. At the same time, blood flow is maintained to the large nephrons with loops of Henle. Reducing GFR at the expenses of excreting wastes can be viewed as a mechanism to conserve body water during periods of water deprivation. | [
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PMID:10739 | Inhibition of inotropic effect of hyperosmotic mannitol by lactate in vitro. | Isolated, isometrically contracting cat papillary muscles were used to evaluate the inotropic interactions of lactic acidosis, hypercarbic acidosis, and lactate ion with hypertonic mannitol. These studies have documented that both lactic acidosis (pH less than 7.0) and lactate ion at a normal pH inhibit the inotropic effect of hyperosmotic mannitol in vitro. In contrast, hypercarbic acidosis does not prevent the inotropic effect of mannitol. Inhibition by lactic acid of mannitol's effects on contractility persists in the presence of beta-receptor blockade. The results suggest that inhibition by severe lactic acidosis of the direct inotropic effect of hyperosmolality in isolated cardiac muscle is mediated by lactate ion rather than acidosis per se. | Inhibition of inotropic effect of hyperosmotic mannitol by lactate in vitro. Isolated, isometrically contracting cat papillary muscles were used to evaluate the inotropic interactions of lactic acidosis, hypercarbic acidosis, and lactate ion with hypertonic mannitol. These studies have documented that both lactic acidosis (pH less than 7.0) and lactate ion at a normal pH inhibit the inotropic effect of hyperosmotic mannitol in vitro. In contrast, hypercarbic acidosis does not prevent the inotropic effect of mannitol. Inhibition by lactic acid of mannitol's effects on contractility persists in the presence of beta-receptor blockade. The results suggest that inhibition by severe lactic acidosis of the direct inotropic effect of hyperosmolality in isolated cardiac muscle is mediated by lactate ion rather than acidosis per se. | [
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PMID:10740 | Renal hydrogen ion secretion after release of unilateral ureteral obstruction. | The effect of 24 h of unilateral ureteral obstruction on HCO3 reabsroption and urinary acidification was studied in dogs. The postobstructed kidney (EK) had a significantly lower glomerular filtration rate and renal plasma flow than the contralateral kidney (CK). Urinary pH prior to HCO3 loading was significantly higher in the EK as was maximal HCO3 reabsorption. Saline loading depressed HCO3 reabsorption to the same degree in both kidneys. Urinary PCO2, during HCO3 loading, and during phosphate infusion, was significantly lower in the EK than the CK. Fractional Na excretion was significantly higher in the EK than the CK after deoxycorticosterone acetate administration. Na2SO4 administration enhanced acid excretion only in the CK. K excretion was significantly lower in the EK than the CK both during HCO3 loading and Na2SO4 administration. There was redistribution of cortical blood flow from the outer cortex toward the inner cortex in the EK as compared to the CK. There was no difference in plasma renin activity from both renal veins. These data demonstrate enhanced proximal H+ secretion (which is abolished by volume expansion) and impaired distal H+ secretion by the postobstructed kidney. The distal defect is likely an effect of a generalized disorder of distal transport in that both K secretion and steroid-responsive Na reabsorption were impaired in the postobstructed kidney. | Renal hydrogen ion secretion after release of unilateral ureteral obstruction. The effect of 24 h of unilateral ureteral obstruction on HCO3 reabsroption and urinary acidification was studied in dogs. The postobstructed kidney (EK) had a significantly lower glomerular filtration rate and renal plasma flow than the contralateral kidney (CK). Urinary pH prior to HCO3 loading was significantly higher in the EK as was maximal HCO3 reabsorption. Saline loading depressed HCO3 reabsorption to the same degree in both kidneys. Urinary PCO2, during HCO3 loading, and during phosphate infusion, was significantly lower in the EK than the CK. Fractional Na excretion was significantly higher in the EK than the CK after deoxycorticosterone acetate administration. Na2SO4 administration enhanced acid excretion only in the CK. K excretion was significantly lower in the EK than the CK both during HCO3 loading and Na2SO4 administration. There was redistribution of cortical blood flow from the outer cortex toward the inner cortex in the EK as compared to the CK. There was no difference in plasma renin activity from both renal veins. These data demonstrate enhanced proximal H+ secretion (which is abolished by volume expansion) and impaired distal H+ secretion by the postobstructed kidney. The distal defect is likely an effect of a generalized disorder of distal transport in that both K secretion and steroid-responsive Na reabsorption were impaired in the postobstructed kidney. | [
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PMID:10741 | Effects of increased O2 and CO2 on acid secretion by dogfish gastric mucosa in vitro. | The gastric mucosa of the dogfish (Squalus acanthias), as usually prepared for in vitro chambered experiments, shows a secretory rate (JH) of about 2 mueq/cm2-h, but a potential difference (PD) of zero. Raising PCO2 from 0.05 to 0.1 atm increases JH by 40% and causes the development of a PD of about 2 mV, mucosal surface positive. Increasing PO2 from 0.9 to 1.9 atm in a hyperbaric chamber (at constant PCO2 = 0.1 atm) doubles JH and increases PD to 5 mV. Transepithelial resistance falls by 20% at high PO2. It appears that the dogfish gastric mucosa, like that of the frog, is rate limited by CO2 diffusion into the tissue from the usual 5% mixture and is also rate limited by the usual O2 levels (unlike the frog), presumably due to its thicker structure and higher O2 consumption. The mucosal-positive PD, which is reversed from all other mucosae studied, is readily explained by separate electrogenic H+ and Cl- pumps, but less readily by schemes embodying a neutral HCl pump. It is not yet known whether the hyperbaric conditions are sufficient to ensure O2 sufficiency. | Effects of increased O2 and CO2 on acid secretion by dogfish gastric mucosa in vitro. The gastric mucosa of the dogfish (Squalus acanthias), as usually prepared for in vitro chambered experiments, shows a secretory rate (JH) of about 2 mueq/cm2-h, but a potential difference (PD) of zero. Raising PCO2 from 0.05 to 0.1 atm increases JH by 40% and causes the development of a PD of about 2 mV, mucosal surface positive. Increasing PO2 from 0.9 to 1.9 atm in a hyperbaric chamber (at constant PCO2 = 0.1 atm) doubles JH and increases PD to 5 mV. Transepithelial resistance falls by 20% at high PO2. It appears that the dogfish gastric mucosa, like that of the frog, is rate limited by CO2 diffusion into the tissue from the usual 5% mixture and is also rate limited by the usual O2 levels (unlike the frog), presumably due to its thicker structure and higher O2 consumption. The mucosal-positive PD, which is reversed from all other mucosae studied, is readily explained by separate electrogenic H+ and Cl- pumps, but less readily by schemes embodying a neutral HCl pump. It is not yet known whether the hyperbaric conditions are sufficient to ensure O2 sufficiency. | [
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PMID:10742 | Depression and the reintegration phase of acute schizophrenia. | The authors found moderate to severe depression in 60% of a group of schizophrenic patients experiencing acute decompensations (N=30). The course of the depression was followed over an 8-week period8,during which patients were treated with depot fluphenazines. There was a statistically significant reduction in depression that closely paralleled the correction of the cognitive disorder. The authors discuss problems in identifying and quantifying depression during acute schizophrenic decompensation and suggest that the Hamilton scale anxiety/depression factor and the BRPS depression factor may be useful diagnositc tools. | Depression and the reintegration phase of acute schizophrenia. The authors found moderate to severe depression in 60% of a group of schizophrenic patients experiencing acute decompensations (N=30). The course of the depression was followed over an 8-week period8,during which patients were treated with depot fluphenazines. There was a statistically significant reduction in depression that closely paralleled the correction of the cognitive disorder. The authors discuss problems in identifying and quantifying depression during acute schizophrenic decompensation and suggest that the Hamilton scale anxiety/depression factor and the BRPS depression factor may be useful diagnositc tools. | [
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PMID:10743 | Self-induced depersonalization syndrome. | The author reports two cases in which depersonalization occurred during the waking consciousness of individuals who had engaged in meditative techniques designed to alter consciousness. Psychiatrists should be aware of this phenomenon, as the number organizations in the "consciousness movement" is increasing, and should ask people manifesting depersonalization about any involvement in activities leading to altered states of consciousness. In some cases it might be appropriate to refer such patients to responsible groups that teach altered consciousness by meditation as an egosyntonic desirable state. The author cautions against the use of phenothiazines in cases where depersonalization is a prominent feature. | Self-induced depersonalization syndrome. The author reports two cases in which depersonalization occurred during the waking consciousness of individuals who had engaged in meditative techniques designed to alter consciousness. Psychiatrists should be aware of this phenomenon, as the number organizations in the "consciousness movement" is increasing, and should ask people manifesting depersonalization about any involvement in activities leading to altered states of consciousness. In some cases it might be appropriate to refer such patients to responsible groups that teach altered consciousness by meditation as an egosyntonic desirable state. The author cautions against the use of phenothiazines in cases where depersonalization is a prominent feature. | [
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PMID:10746 | Generic and trade-name antipsychotic drugs: clinical equivalence. | The clinical inequivalence of generic versus trade-name drugs has been reported for nonpsychiatric drugs but rarely for psychotropic drugs. Recent expiration of patents on some psychotropic drugs has made the evaluation of the clinical equivalence of generic versus trade-name drugs a matter of interest from methodological, sociopolitical, and economic aspects. The authors discuss these points, with emphasis on methodology, in their report of a double-blind study of the efficacy of chlorpromazine and Thorazine in the treatment of 54 acute schizophrenic patients. An analysis designed to infer the maximum possible advantage of Thorazine over generic chlorpromazine indicated that differences between the two were clinically insignificant. | Generic and trade-name antipsychotic drugs: clinical equivalence. The clinical inequivalence of generic versus trade-name drugs has been reported for nonpsychiatric drugs but rarely for psychotropic drugs. Recent expiration of patents on some psychotropic drugs has made the evaluation of the clinical equivalence of generic versus trade-name drugs a matter of interest from methodological, sociopolitical, and economic aspects. The authors discuss these points, with emphasis on methodology, in their report of a double-blind study of the efficacy of chlorpromazine and Thorazine in the treatment of 54 acute schizophrenic patients. An analysis designed to infer the maximum possible advantage of Thorazine over generic chlorpromazine indicated that differences between the two were clinically insignificant. | [
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PMID:10747 | Coffee consumption among psychiatric inpatients. | Of 135 patients on an acute psychiatric ward, 34 were "high users" of coffee. The high users tended to be older, single, and have diagnoses of psychosis. They showed significantly more state anxiety than other patients, but there were no differences in trait anxiety or MMPI scores. Further research is suggested to determine whether high caffeine consumption among inpatients may be related to staff coffee-drinking behavior and/or treatment with anticholinergic drugs. | Coffee consumption among psychiatric inpatients. Of 135 patients on an acute psychiatric ward, 34 were "high users" of coffee. The high users tended to be older, single, and have diagnoses of psychosis. They showed significantly more state anxiety than other patients, but there were no differences in trait anxiety or MMPI scores. Further research is suggested to determine whether high caffeine consumption among inpatients may be related to staff coffee-drinking behavior and/or treatment with anticholinergic drugs. | [
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PMID:10748 | Catatonialike symptomatology and withdrawal dyskinesias. | The authors describes a patient who presented catatonialike symptoms and dyskinesias associated with glutethimide discontinuance and antihistamine use. He hypothesizes that altered dopamine metabolism may produce some of the unusual neuropsychiatric characteristics of glutethimide withdrawal. Drug-withdrawal catatonia may be an additional entity in the differential diagnosis of catatonialike states of organic etiology. | Catatonialike symptomatology and withdrawal dyskinesias. The authors describes a patient who presented catatonialike symptoms and dyskinesias associated with glutethimide discontinuance and antihistamine use. He hypothesizes that altered dopamine metabolism may produce some of the unusual neuropsychiatric characteristics of glutethimide withdrawal. Drug-withdrawal catatonia may be an additional entity in the differential diagnosis of catatonialike states of organic etiology. | [
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PMID:10751 | Formal presentation at a scientific meeting. | The giving of a ten minute scientific communication is an art form peculiar to researchers who frequently fail to research the technology required for the performance. Careful selection of the scientific material to be included, the audio-visual aids to support it, and adequate rehearsal before presentation to a critical audience are vital to the success of the presentation. | Formal presentation at a scientific meeting. The giving of a ten minute scientific communication is an art form peculiar to researchers who frequently fail to research the technology required for the performance. Careful selection of the scientific material to be included, the audio-visual aids to support it, and adequate rehearsal before presentation to a critical audience are vital to the success of the presentation. | [
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PMID:10752 | Intravenous flunitrazepam as an anesthetic induction agent. | The effects of the fluorinated benzodiazepine compound flunitrazepam were studied in eighty patients. The drug was administered intravenously in a standard dose of 2 mg, 3 mg, or 4 mg to supplement lumbar epidural analgesia. Induction was smooth and pleasant. The sleep onset time was dose related and exceeded one minute in the majority of patients. Sleep was invariably produced in patients receiving 4 mg but at lower dosage some patients failed to become unconscious. Pain in the arm during injection was a common feature. The respiratory rate was slightly increased, but in two patients apnoea occurred at induction. The cardiovascular system was minimally depressed with a small decrease in systolic blood pressure and pulse rate. Recovery from sleep was slow but sequelae were minimal. The sedative and amnesic properties contributed significantly to the high rate of patient acceptance. | Intravenous flunitrazepam as an anesthetic induction agent. The effects of the fluorinated benzodiazepine compound flunitrazepam were studied in eighty patients. The drug was administered intravenously in a standard dose of 2 mg, 3 mg, or 4 mg to supplement lumbar epidural analgesia. Induction was smooth and pleasant. The sleep onset time was dose related and exceeded one minute in the majority of patients. Sleep was invariably produced in patients receiving 4 mg but at lower dosage some patients failed to become unconscious. Pain in the arm during injection was a common feature. The respiratory rate was slightly increased, but in two patients apnoea occurred at induction. The cardiovascular system was minimally depressed with a small decrease in systolic blood pressure and pulse rate. Recovery from sleep was slow but sequelae were minimal. The sedative and amnesic properties contributed significantly to the high rate of patient acceptance. | [
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PMID:10757 | In vitro effects of certain neurohumors on ultrastructural change of the chick embryonic thyroid gland. | In vitro effects of certain neurohumors, on ultrastructure of 14 days old chick embryonic thyroid gland, has been studied. When the chick embryonic thyroid gland was cultivated in vitro, in the medium containing neurohumors like acetylcholine, adrenaline and histamine for a definite period in a particular sequence and dose, has resulted almost similar ultrastructural changes as seen in the hyperactive thyroid gland. | In vitro effects of certain neurohumors on ultrastructural change of the chick embryonic thyroid gland. In vitro effects of certain neurohumors, on ultrastructure of 14 days old chick embryonic thyroid gland, has been studied. When the chick embryonic thyroid gland was cultivated in vitro, in the medium containing neurohumors like acetylcholine, adrenaline and histamine for a definite period in a particular sequence and dose, has resulted almost similar ultrastructural changes as seen in the hyperactive thyroid gland. | [
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PMID:10758 | Histological response of various endocrine glands after administration of certain neurohumors in chicks. | Histological response of various endocrine glands like pituitary, adrenal, testes and pancreas after administration of certain neurohumors like acetylcholine, adrenaline and histamine in a particular dose and sequence, has been carried out in white leghorn chicks. Result of this study revealed that administration of these neurohumors produced definite changes in various endocrines. Histological changes are more prominent in pituitary and adrenal glands, whereas, pancreas and testes did not reveal much influence of these neurohumors. | Histological response of various endocrine glands after administration of certain neurohumors in chicks. Histological response of various endocrine glands like pituitary, adrenal, testes and pancreas after administration of certain neurohumors like acetylcholine, adrenaline and histamine in a particular dose and sequence, has been carried out in white leghorn chicks. Result of this study revealed that administration of these neurohumors produced definite changes in various endocrines. Histological changes are more prominent in pituitary and adrenal glands, whereas, pancreas and testes did not reveal much influence of these neurohumors. | [
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