5,021 results on '"Aminopyrine"'
Search Results
402. Inhibition of human platelet cathepsin A by non-steroidal anti-inflammatory drugs--in vitro study
- Author
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Halina Ostrowska
- Subjects
Blood Platelets ,Aspirin ,Anti-Inflammatory Agents, Non-Steroidal ,Indomethacin ,Cathepsin A ,Humans ,Phenacetin ,Carboxypeptidases ,In Vitro Techniques ,Aminopyrine ,Salicylic Acid ,Salicylates - Abstract
Since the lysosomal proteases appear at site of inflammation they may be a target for non-steroidal anti-inflammatory drugs (NSAIDs). In in vitro study the inhibition of human platelet cathepsin A by NSAIDs was found. Indomethacin, phenacetin and aminophenazone were the most potent inhibitors of cathepsin A. Acetylsalicylic acid added to platelet lysate inhibited cathepsin A in the same extent as salicylate. The inhibition was time-dependent and reversed after dialysis. Mixed type of inhibition by salicylate was shown.
- Published
- 1996
403. Continuous monitoring of 13C-aminopyrine metabolism in rats: effects of cold exposure and noradrenaline
- Author
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François Lascaux, François Mion, Y. Minaire, Marina Rousseau, Alain Géloën, and Roger Guilluy
- Subjects
Male ,medicine.medical_specialty ,Cold exposure ,Endogeny ,General Biochemistry, Genetics and Molecular Biology ,Rats, Sprague-Dawley ,Norepinephrine ,Cytochrome P-450 Enzyme System ,In vivo ,Internal medicine ,medicine ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,Aminopyrine ,Demethylation ,Dose-Response Relationship, Drug ,Chemistry ,Hepatic cytochrome ,Continuous monitoring ,General Medicine ,Metabolism ,Rats ,Cold Temperature ,Endocrinology ,Liver ,Linear Models ,Perfusion - Abstract
A system was developed to allow constant monitoring of hepatic cytochrome P450 activity in awake and unrestrained rats. A continuous 13C-aminopyrine perfusion was performed, and breath samples obtained for endogenous CO2 production and 13C measurements, to calculate 13C O2 production due to aminopyrine demthylation. Increasing doses of 13C-aminopyrine produced a hyperbolic increase of expired 13CO2, compatible with an in vivo measurement of enzymatic activity. Acute-cold exposure of the rats during 13C-aminopyrine perfusion produced a two-fold increase of endogenous CO2 production, together with a 27% increased 13C-aminopyrine metabolism (p0.05 vs basal conditions). In contrast, noradrenaline (20 microg/kg BW/min), despite a similar effect on energy expenditure, did not significantly change 13C-aminopyrine metabolism. Acute-cold exposure is known to stimulate both adrenal catecholamine secretion and the sympathetic nervous system. The observed difference in 13C-aminopyrine demthylation during cold exposure and nonadrenaline perfusion, therefore, could be due to a more specific effect of adrenal catecholamines on liver aminopyrine metabolism. These results suggest the possibility of prolonged in vivo monitoring of liver metabolism pathways such as aminopyrine demethylation, thus allowing the study of drug acute interactions with cytochrome P450 system.
- Published
- 1996
404. Reactive metabolites and agranulocytosis
- Author
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Jack Uetrecht
- Subjects
biology ,Hypochlorous acid ,Chemistry ,Hematology ,General Medicine ,Oxidative phosphorylation ,Pharmacology ,Neutrophil Activation ,Hypochlorous Acid ,chemistry.chemical_compound ,Antigen ,Myeloperoxidase ,Immunology ,biology.protein ,Cytotoxic T cell ,Humans ,Antibody ,Stem cell ,Cytotoxicity ,Aminopyrine ,Clozapine ,Agranulocytosis - Abstract
Central to most hypotheses of the mechanism of idiosyncratic drug-induced blood dyscrasias is the involvement of reactive metabolites. In view of the reactive nature of the majority of such metabolites, it is likely that they are formed by, or in close proximity to the blood cells affected. The major oxidative system of neutrophils generates hypochlorous acid. We have demonstrated that the drugs associated with the highest incidence of agranulocytosis are oxidized to reactive metabolites by hypochlorous acid and/or activated neutrophils. There are many mechanisms by which such reactive metabolites could induce agranulocytosis. In the case of aminopyrine-induced agranulocytosis, most cases appear to involve drug-dependent anti-neutrophil antibodies, and these are likely to be induced by cell membrane antigens modified by the reactive metabolite of aminopyrine. The target of agranulocytosis associated with many other drugs is usually neutrophil precursors and may involve cytotoxicity or a cell-mediated immune reaction induced by a reactive metabolite. In the case of aplastic anaemia, there is evidence in some cases for involvement of cytotoxic T cells, which could either be induced by metabolites generated by neutrophils, or more likely, by reactive metabolites generated by stem cells.
- Published
- 1996
405. Separation of five antipyretic analgesics by micellar electrokinetic capillary chromatography
- Author
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Y, Chen, F M, Han, and Z B, Yuan
- Subjects
Electrophoresis ,Chromatography ,Phenylbutazone ,Anti-Inflammatory Agents, Non-Steroidal ,Dipyrone ,Aminopyrine ,Antipyrine - Abstract
The derivatives of antipyrine and phenylbutazone are important antipyretic analgesics commonly used in clinical medicine. Although high performance liquid chromatography has been the conventional method used for the analysis of these drugs, in recent years capillary electrophoresis was validated to be a useful method in the analysis of antipyretic analgesics. However, there has been no report on the separation of antipyrine (AP), 4-aminoantipyrine (4-AAP), aminopyrine (APY), dipyrone (DIP) and phenylbutazone (PHE) in the literature. In this paper, a micellar electrokinetic capillary chromatographic (MECC) separation method was described for the five antipyretic analgesics.
- Published
- 1996
406. A qualitative method for assessing the C-14 labelling position in [C-14]-dimethyl aminoantipyrine (aminopyrine)
- Author
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UCL - MD/MINT - Département de médecine interne, UCL - MD/FARM - Ecole de pharmacie, Levêque, Philippe, Gallez, Bernard, UCL - MD/MINT - Département de médecine interne, UCL - MD/FARM - Ecole de pharmacie, Levêque, Philippe, and Gallez, Bernard
- Abstract
[C-14]-Aminopyrine is a well known compound which is widely used for the evaluation of the hepatic function (breath test). As this breath lest is based upon N-demethylation, it is essential to verify the labelling position in order to guarantee relevant results. We propose an enzymatic method based on collection of (CO2)-C-14 produced after specific in vitro N-demethylation in a medium containing horseradish peroxidase, formaldehyde dehydrogenase and formate dehydrogenase. This assay allows for a qualitative monitoring of the labelling position.
- Published
- 1998
407. Roles of sigma receptors in isolated guinea pig parietal cells
- Author
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T, Suzuki, N, Tani, N, Mutoh, and T, Miwa
- Subjects
Male ,Parietal Cells, Gastric ,Isotope Labeling ,Guinea Pigs ,Cyclic AMP ,Animals ,Receptors, sigma ,Calcium ,Carbon Radioisotopes ,Aminopyrine ,Tritium ,Guanidines ,Cells, Cultured - Abstract
Sigma receptor involvement in the oxyntic mechanism of gastric parietal cells was investigated using isolated guinea pig parietal cells. Using the 14C-aminopyrine accumulation method, di(orthotolyl)guanidine (DTG), a sigma receptor agonist, demonstrated peak stimulation of acid production at a concentration of 5 x 10(-5) M. The DTG-induced stimulatory effect on 14C-aminopyrine accumulation in preparations enriched in parietal cells was inhibited by haloperidol, a DTG inhibitor, and omeprazole, a proton pump inhibitor, in a concentration-dependent manner. Assessment of the interaction between DTG and agonists for histamine, gastrin, and muscarine receptors demonstrated a potentiating interaction effect on acid production only when parietal cells were exposed to both DTG and histamine. A receptor-binding assay using 3H-DTG revealed two sigma receptor subtypes, sigma 1 and sigma 2, on the crude membranes of parietal cells. There was a direct relationship between DTG dose and intracellular Ca2+ concentration, but there was no change in intracellular cyclic adenosine 5'-monophosphate (cAMP) concentration when parietal cells were exposed to DTG. These results demonstrate that sigma receptors exist on guinea pig gastric parietal cells and suggest that they play a role in acid production via an increase in intracellular Ca2+ concentration.
- Published
- 1995
408. [13C]Aminopyrine breath test detects altered liver metabolism caused by low-dose oral contraceptives
- Author
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Peter D. Klein, David Y. Graham, and Antone R. Opekun
- Subjects
Adult ,Male ,medicine.medical_specialty ,Physiology ,medicine.drug_class ,media_common.quotation_subject ,Mixed Function Oxygenases ,Liver disease ,Liver Function Tests ,Oral administration ,Internal medicine ,Medicine ,Humans ,Aminopyrine ,Menstrual cycle ,media_common ,Breath test ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Hepatology ,medicine.disease ,Endocrinology ,Breath Tests ,Liver ,Estrogen ,Toxicity ,Female ,Liver function ,business ,Contraceptives, Oral - Abstract
The [13C]aminopyrine breath test measures hepatic mixed function oxidase activity. The cumulative percent dose recovered over 2 hr is a sensitive indicator of hepatic dysfunction; valuesor = 7.0% have been shown to indicate severe liver disease. Previous studies have suggested that the test results may be influenced by the use of oral contraceptives steroids. We compared the results from five non-oral contraceptive-using women with those from 31 women whose duration of oral contraceptive steroid usage ranged from 4 to 204 months. The women were taking one of four oral contraceptive formulations that differed in the amounts of estrogen (20, 35, or 50 micrograms with 1 mg progesterone) and progesterone (35 micrograms estrogen with stepped levels of progesterone of 0.5, 0.75, and 1.0 mg). The [13C]aminopyrine breath test was performed on days 21 and 28 of the menstrual cycle. Cumulative percent dose recovery values among the normal menstrual cycle of non-oral contraceptive steroid-using women were 12.1 +/- 1.6 and 11.8 +/- 1.5% (mean +/- SD). In contrast, oral contraceptive steroid users showed a marked reduction in cumulative percent dose recovery at 21 days, averaging 6.1 +/- 2.3% (P0.001), and returned to normal values (10.2 +/- 3.5%) at 28 days in most women(seven days after oral contraceptive steroid usage was paused). The adverse impact on hepatic mixed function oxidase by oral contraceptive formulations did not differ on the basis of estrogen or progesterone content. The adverse impact of oral contraceptive usage on the mixed function oxidase activity measured by the [13C]aminopyrine breath test must be considered for women of childbearing potential.
- Published
- 1995
409. [Amidazophen. Yes or no?]
- Author
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J, Jákó and G, Arató
- Subjects
Adult ,Fever ,Anti-Inflammatory Agents, Non-Steroidal ,Analgesics, Non-Narcotic ,Kidney Tubular Necrosis, Acute ,Lupus Nephritis ,Pregnancy Complications ,Fatal Outcome ,Pregnancy ,Humans ,Lupus Erythematosus, Systemic ,Female ,Aminopyrine ,Acetaminophen - Abstract
The authors compare the side effects and hazards of the use of Paracetamol and Amidazophen on the basis of literary data. They draw the conclusion that in case of illnesses accompanied by fever, Amidazophen is preferable as an antifebrile, on both professional and cost-effectiveness grounds. This conclusion is supported by an acute tubularis necrosis case, where a direct link is suspected between the use of Paracetamol as an antifebrile and the development of kidney damage.
- Published
- 1995
410. Aminopyrine infusion breath test for the determination of changes in P450 metabolism in vivo
- Author
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A. N. Kotake, M. L. Phan, T. J. Shinn, S. K. Kuwahara, and B. D. Schreider
- Subjects
Health, Toxicology and Mutagenesis ,Analgesic ,Pharmacology ,Toxicology ,Biochemistry ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Cytochrome P-450 Enzyme System ,In vivo ,medicine ,Animals ,Cytochrome P-450 Enzyme Inhibitors ,Expiration ,Carbon Radioisotopes ,Cimetidine ,Aminopyrine ,Breath test ,medicine.diagnostic_test ,Chemistry ,General Medicine ,Metabolism ,Rats ,Breath Tests ,Aminophenazone ,Perfusion ,medicine.drug - Abstract
1. An osmotic mini-pump was used to maintain a constant infusion of radiolabelled [N-dimethyl-14C] aminopyrine into a rat. After implanting the mini-pump, 14CO2 expiration rate was constant within 12 h, and this rate was maintained for 192 h. 2. Treatment with 2-diethylaminoethyl-2,2-diphenylvalerate HCl (SKF 525-A) or cimetidine, inhibitors of P450-dependent metabolism, resulted in both dose- and time-dependent inhibition of the expiration of 14CO2.
- Published
- 1995
411. A role for calcineurin (protein phosphatase-2B) in the regulation of glutamate release
- Author
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Talvinder S. Sihra, Christophe Pouzat, Angus C. Nairn, Peter Kloppenburg, and Zhixin Lin
- Subjects
medicine.medical_specialty ,Biophysics ,Glutamic Acid ,Biology ,Pharmacology ,Biochemistry ,Exocytosis ,Tacrolimus ,Membrane Potentials ,Dephosphorylation ,Internal medicine ,Protein Phosphatase-2B ,medicine ,Phosphoprotein Phosphatases ,Animals ,Phosphorylation ,Aminopyrine ,Molecular Biology ,Egtazic Acid ,Cerebral Cortex ,Calcineurin ,Glutamate receptor ,Drug Synergism ,Cell Biology ,Rats ,Cytosol ,Endocrinology ,medicine.anatomical_structure ,Cerebral cortex ,Calcium ,Calmodulin-Binding Proteins ,Synaptosomes - Abstract
Previous studies have shown that 4-aminopyridine (4AP) induced Ca-influx effects the release of glutamate from nerve terminals (synaptosomes) isolated from rat cerebral cortex. We now show that the Ca-dependent component of this release is potentiated by preincubation of the synaptosomes with the immunosuppressant, FK506, an inhibitor of protein phosphatase-2B (calcineurin). FK506 did not inhibit the Ca-independent release of glutamate from a cytosolic pool. Examination of the effect of FK506 on the influx of Ca elicited by 4AP indicated that inhibition of calcineurin activity resulted in an increase of voltage-dependent Ca-influx. Based on these results, we suggest that protein dephosphorylation effected by calcineurin may suppress voltage-dependent Ca-channel activity and in so doing inhibits evoked glutamate release. Activation of calcineurin produced by initial Ca-entry may represent a negative feedback to limit the activity of Ca-channels coupled to the release of glutamate.
- Published
- 1995
412. Platelet-activating factor stimulates gastric acid secretion in isolated rabbit gastric glands
- Author
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André Bado, L. Moizo, Iradj Sobhani, P. Braquet, T. Tarrade, J.-P. Laigneau, and M. J. M. Lewin
- Subjects
Male ,medicine.medical_specialty ,Carbachol ,Thienopyridines ,Physiology ,Biology ,In Vitro Techniques ,Gastric Acid ,chemistry.chemical_compound ,Physiology (medical) ,Gastric glands ,Internal medicine ,medicine ,Extracellular ,Gastric mucosa ,Animals ,Platelet Activating Factor ,Aminopyrine ,Egtazic Acid ,Fluorescent Dyes ,Hepatology ,Platelet-activating factor ,Dose-Response Relationship, Drug ,Gastroenterology ,Biological Transport ,Azepines ,Triazoles ,Famotidine ,Kinetics ,Thiazoles ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Verapamil ,Gastric Mucosa ,Gastric acid ,Calcium ,Rabbits ,Intracellular ,Histamine ,medicine.drug - Abstract
We examined the effect of platelet-activating factor (PAF) on gastric acid secretion by isolated rabbit gastric glands as determined by [14C]aminopyrine ([14C]AP) uptake. PAF, histamine, and carbachol time- and concentration-dependently stimulated [14C]AP uptake, with estimated half-maximal effective concentrations of 60 pM, 0.25 microM, and 0.1 microM, respectively. PAF-induced [14C]AP uptake was inhibited by the specific PAF antagonists BN-50727 and SR-27417 and by the proton pump inhibitors omeprazole and lansoprazole. However, the H2-receptor antagonist famotidine had no effect. Buffering extracellular Ca2+ by ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid resulted in a shift to the right of the time-course effect of PAF without altering the maximal response, whereas buffering intracellular Ca2+ by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid 2-acetoxymethyl ester, as well as blocking Ca2+ channels by verapamil, inhibited PAF-induced [14C]AP uptake. Intracellular Ca2+ concentration in isolated rabbit gastric glands, as measured by fura 2-acetoxymethyl ester, concentration-dependently increased in response to PAF, to a maximum of 1.5-fold for 0.1 microM. These results suggest that PAF stimulates gastric acid secretion via specific receptors activating intracellular Ca2+ mobilization, which could be located on the parietal cells.
- Published
- 1995
413. [Case history--red urine]
- Author
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Vouzémoix
- Subjects
Adult ,Drug Combinations ,Phenobarbital ,Porphyria, Acute Intermittent ,Humans ,Female ,Aminopyrine - Published
- 1995
414. [Studies on histamine H2-receptor antagonistic property of FRG-8813, a novel anti-ulcer drug]
- Author
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Sadayoshi Onodera, Haruo Ohnishi, Masato Tanaka, Tetsuaki Yamaura, Niro Inaba, Takao Suzuki, and Masahiro Shibata
- Subjects
Male ,Time Factors ,Pyridines ,Guinea Pigs ,Pharmacology ,In Vitro Techniques ,chemistry.chemical_compound ,Histamine H2 receptor ,Piperidines ,Acetamides ,medicine ,Gastric mucosa ,Potency ,Animals ,Cimetidine ,Aminopyrine ,Cerebral Cortex ,Dose-Response Relationship, Drug ,Myocardial Contraction ,Stimulation, Chemical ,Famotidine ,Schild regression ,medicine.anatomical_structure ,chemistry ,Histamine H2 Antagonists ,Gastric Mucosa ,Antagonism ,Histamine ,medicine.drug - Abstract
The present study was conducted to investigate the histamine H2-receptor antagonistic property of FRG-8813 by using isolated guinea pig right atria, gastric cells and cerebral cortex preparations. FRG-8813 inhibited the histamine-induced positive chronotropic response of the right atria and shifted the concentration-response curve of histamine to the right with suppression of the maximal response. Although the inhibitory effect of FRG-8813 was enhanced in a time-dependent manner and long-lasting, the antagonism was reversible. The potency of FRG-8813 was 2 times and 50 times greater than those of famotidine and cimetidine, respectively. FRG-8813 decreased the histamine-induced [14C]aminopyrine accumulation in gastric cells. Schild plot analysis showed that the slopes of FRG-8813, famotidine and cimetidine were 1.56, 1.40 and 1.07, respectively, suggesting that the mode of the antagonism of FRG-8813 is also unsurmountable in gastric cells. The lack of effect on dbcAMP- and bethanechol-induced [14C]aminopyrine accumulations indicated the selectivity of FRG-8813 for histamine H2-receptor. As in the right atria, the potency of H2-antagonism was 1.5 times and 40 times greater than those of famotidine and cimetidine, respectively. In the [3H]tiotidine binding study of the cerebral cortex preparation, the Ki values showed that the affinity of FRG-8813 was 2 times and 80 times more potent than those of famotidine and cimetidine, respectively. In conclusion, FRG-8813 is an unsurmountable and selective histamine H2-receptor antagonist with 2 times greater potency than famotidine. The antagonistic activity is reversible in spite of the time-dependent increase of the antagonism.
- Published
- 1995
415. Metabolism of aminopyrine and derivatives in man: in vivo study of monomorphic and polymorphic metabolic pathways
- Author
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Carmen Martínez, Julio Benítez, and José A. G. Agúndez
- Subjects
Adult ,Male ,Adolescent ,Health, Toxicology and Mutagenesis ,Administration, Oral ,Urine ,Pharmacology ,Toxicology ,Biochemistry ,chemistry.chemical_compound ,Pharmacokinetics ,Oral administration ,medicine ,Humans ,Mephenytoin ,Aminopyrine ,Biotransformation ,Chemistry ,General Medicine ,Metabolism ,Middle Aged ,Debrisoquine ,Aminophenazone ,Female ,Caffeine ,medicine.drug - Abstract
1. The main metabolic pathways involved in the biodisposition of aminopyrine have been monitored in vivo in 60 healthy volunteers by measuring the amount of parent drug and metabolites recovered in the urine 24 h after oral administration of 250 mg aminopyrine. 2. The amount of metabolites in the 24-h urine was (mean +/- SD of 60 individuals): unchanged aminopyrine, 0.2 +/- 0.2 mg; methyl aminoantipyrine, 4.5 +/- 2.8 mg; formyl aminoantipyrine, 18.5 +/- 10.1 mg; aminoantipyrine, 9.2 +/- 6.6 mg; and acetyl aminoantipyrine, 31.8 +/- 21.1 mg. 3. Large interindividual differences (12-200-fold changes) are present in all the metabolic steps involved in aminopyrine biotransformation. These differences are not related to gender, intake of caffeine or alcohol, or known drug-metabolizing polymorphisms such as those involved in debrisoquine or mephenytoin metabolism. In contrast, smoking resulted in a decrease in the N(4)-demethylation ratio (p = 0.011). 4. The interindividual differences followed an apparently normal distribution in the N(4)- and N(2)-dimethylation and formylation pathways (p > 0.1). In contrast, acetylation follows a polymorphic distribution (p < 0.03), with an apparent antimode ratio close to 4. With the exception of the acetylation pathway, all of the metabolic ratios correlated between themselves (p < 0.001).
- Published
- 1995
416. Inhibition of acid secretory response and induction of ornithine decarboxylase and its mRNA by TGF alpha and EGF in isolated rat gastric glands
- Author
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Stanislaw J. Konturek, Jerzy Ostrowski, Krzysztof Wojciechowski, and L Trzeciak
- Subjects
medicine.medical_specialty ,TGF alpha ,Eflornithine ,Physiology ,Clinical Biochemistry ,Molecular Sequence Data ,Spermine ,Biology ,In Vitro Techniques ,Ornithine Decarboxylase ,Biochemistry ,Polymerase Chain Reaction ,Ornithine decarboxylase ,Gastric Acid ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Epidermal growth factor ,Internal medicine ,Gastric glands ,medicine ,Gastric mucosa ,Animals ,RNA, Messenger ,Rats, Wistar ,Aminopyrine ,Parietal cell ,DNA Primers ,Base Sequence ,Epidermal Growth Factor ,Transforming Growth Factor alpha ,Rats ,medicine.anatomical_structure ,chemistry ,Gastric Mucosa ,Enzyme Induction ,Gastric acid ,Histamine - Abstract
TGF alpha shows structural and functional homology to EGF, but TGF alpha's mitogenic potency is greater. Our previous study showed that EGF may inhibit parietal cell secretory response through the induction of ornithine decarboxylase (ODC). The aim of this study was to determine parietal cell acid production in vitro in response to stimulation by TGF alpha and EGF and to compare the effect of these two growth factors on ODC activity and ODC mRNA in isolated rat gastric glands. 45 min treatment with TGF alpha and EGF had no effect on basal acid production but did inhibit histamine-stimulated acid production in a dose dependent manner. The two growth factors did not inhibit histamine-stimulated aminopyrine (AP) uptake from incubation medium with concentration of KCl increased from 5 to 70 mM. In the presence of specific ODC inhibitor, alpha-difluoromethylornithine (DFMO), both EGF and TGF alpha failed to inhibit histamine-stimulated AP accumulation. Polyamine spermine also inhibited AP accumulation but this inhibitory effect was not affected by DFMO. After 1 h treatment with TGF alpha and EGF, ODC activities increased to an average 283 +/- 78% and 227 +/- 64% above the basal activity, respectively. 30 min treatment of gastric glands with TGF alpha and EGF resulted in, respectively, 2.9 +/- 0.4- and 2.7 +/- 0.5-fold increases of ODC mRNA level, as assessed by RT-PCR.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
417. Relationship of the aminopyrine breath test and the Child-Pugh score to urinary sodium retention in patients with liver cirrhosis
- Author
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G, Wensing, E, Lotterer, H, Ahlsdorf, C F, Kügler, E G, Hahn, and W E, Fleig
- Subjects
Adult ,Liver Cirrhosis ,Male ,Breath Tests ,Liver Function Tests ,Reference Values ,Sodium ,Humans ,Female ,Middle Aged ,Aminopyrine ,Kidney Function Tests ,Aged - Abstract
This study investigated the relationship between urinary sodium excretion and liver function, as assessed by the aminopyrine breath test (ABT) and conventional parameters, in 62 patients with cirrhosis kept on a constant salt diet. Urinary sodium excretion was related non-linearly to the ABT (r = 0.76). Less significant correlations were observed to the Child-Pugh score (r = -0.65), cholinesterase (r = 0.58), bilirubin (r = -0.56), albumin (r = 0.51) and prothrombin time (r = 0.49). When patients were arbitrarily divided into 6 groups according to the ABT, sodium excretion balanced the sodium intake up to a 50% reduction in ABT. In groups with more than a 50% reduction sodium retention occurred. When patients were grouped according to the Child-Pugh score, urinary salt output was balanced in patients with scores of 5 and 6 and decreased in patients with scores greater six. However, the change in sodium output from normal salt excretion to sodium retention was less pronounced in patients grouped according to the Child-Pugh score than in patients grouped according to the ABT. The results suggest a non-linear relationship between the impairment in hepatic and renal function in cirrhosis. They are compatible with the concept of a threshold of hepatic function necessary to maintain normal renal function.
- Published
- 1995
418. Oxidation of aminopyrine by hypochlorite to a reactive dication: possible implications for aminopyrine-induced agranulocytosis
- Author
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Earl Macknight, Hing Man Ma, Robert McClelland, and Jack Uetrecht
- Subjects
Magnetic Resonance Spectroscopy ,Hypochlorous acid ,Neutrophils ,chemistry.chemical_element ,Hypochlorite ,Toxicology ,Photochemistry ,Chloride ,Mass Spectrometry ,Ion ,chemistry.chemical_compound ,Isotopes ,Cations ,medicine ,Chlorine ,Humans ,Hydrogen peroxide ,Aminopyrine ,Iminium ,General Medicine ,Deuterium ,Dication ,Hypochlorous Acid ,Kinetics ,chemistry ,Oxidation-Reduction ,medicine.drug ,Agranulocytosis - Abstract
Aminopyrine is associated with a high incidence of agranulocytosis. It is known to be oxidized by peroxidases and hypochlorous acid to a blue cation radical. It has been proposed that the mechanism by which hypochlorous acid oxidizes aminopyrine to a cation radical involves N-chlorination followed by loss of a chlorine radical. Another possible mechanism is loss of HCl to form an iminium ion and subsequent reaction with another molecule of aminopyrine and a hydrogen ion to form two radical cations. This mechanism would lead to incorporation of a hydrogen from water; however, using a deuterated analog, we found no hydrogen incorporation, thus providing strong evidence against this mechanism. Using a stopped-flow diode array spectrophotometer to study the reaction between aminopyrine and hypochlorous acid, an intermediate with a lambda max at approximately 420 nm was observed in the formation of the cation radical. We propose that this represents a dication formed by the loss of chloride ion from N-chloroaminopyrine. This intermediate is very reactive, with a half-life of approximately 15 ms, and in addition to being the precursor of the cation radical, it also appears to react with two molecules of water to form several other products that were observed and are consistent with the proposed dication intermediate. Similar stable products were formed when amino-pyrine was oxidized by the combination of myeloperoxidase, hydrogen peroxide, and chloride or activated neutrophils. The reactive dication formed by neutrophil-derived hypochlorous acid could be responsible for aminopyrine-induced agranulocytosis.
- Published
- 1995
419. Comparative effects of GLP-1-(7-36) amide, oxyntomodulin and glucagon on rabbit gastric parietal cell function
- Author
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Bernard Thorens, Alain Kervran, Frédéric Hollande, Dominique Bataille, and L Gros
- Subjects
endocrine system ,medicine.medical_specialty ,Glucagon-Like Peptides ,Biology ,Glucagon ,chemistry.chemical_compound ,Parietal Cells, Gastric ,Glucagon-Like Peptide 1 ,Internal medicine ,Amide ,medicine ,Cyclic AMP ,Animals ,RNA, Messenger ,Aminopyrine ,Parietal cell ,Pharmacology ,digestive, oral, and skin physiology ,Blotting, Northern ,Glucagon-like peptide-1 ,Peptide Fragments ,Oxyntomodulin ,Endocrinology ,medicine.anatomical_structure ,Somatostatin ,chemistry ,Rabbits ,hormones, hormone substitutes, and hormone antagonists ,Histamine - Abstract
We have investigated in vitro, the effects of glucagon-like peptide-1-(7-36) amide (GLP-1-(7-36) amide), oxyntomodulin and glucagon on two rabbit parietal cell-enriched fractions (F3, F3n), with parietal cell contents of 60% and 88%, respectively. Histamine (10(-5) M) stimulated [14C]aminopyrine accumulation to an amount of 850% in excess of the basal level, whereas GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10(-6) M) induced increases of 50% and 30%, respectively. With a histamine concentration of 10(-6) M, [14C]aminopyrine accumulation was stimulated to 498% in excess of the basal level; GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10(-7) M) induced increases of 18% and 15%, respectively. With these parameters, oxyntomodulin[19-37] and glucagon were without effect. Specific binding of [125I]GLP-1-(7-36) amide to parietal cell plasma membranes was inhibited dose-dependently by GLP-1-(7-36) amide, oxyntomodulin and glucagon with inhibitory concentrations of 0.25 nM, 65 nM and 800 nM, respectively. No specific binding of [125I]oxyntomodulin or [125I]glucagon was detectable. GLP-1-(7-36) amide receptor mRNA was only detected in parietal cell-enriched fractions. GLP-1-(7-36) amide, oxyntomodulin and glucagon stimulated parietal cell cAMP production to similar maximal levels with median values close to 0.28 nM, 10.5 nM and 331.7 nM, whereas oxyntomodulin[19-37] had no effect. The maximal cAMP production induced by GLP-1-(7-36) amide, oxyntomodulin or glucagon was additive to that induced by histamine.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
420. Aminopyrine breath test improves long-term prognostic evaluation in patients with alcoholic cirrhosis in Child classes A and B
- Author
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Olivier Thys, Daniel Urbain, Vinciane Muls, and Hamphrey Ham
- Subjects
Alcoholic liver disease ,medicine.medical_specialty ,Cirrhosis ,Time Factors ,Gastroenterology ,Severity of Illness Index ,Liver Cirrhosis, Alcoholic ,Internal medicine ,Severity of illness ,medicine ,Humans ,In patient ,Aminopyrine ,Survival analysis ,Breath test ,Hepatology ,medicine.diagnostic_test ,business.industry ,Proportional hazards model ,medicine.disease ,Prognosis ,Survival Analysis ,digestive system diseases ,Breath Tests ,Survival study ,business - Abstract
In a 4-year survival study, we evaluated the prognostic value of the aminopyrine breath test and the Child-Turcotte-Pugh score in 190 alcoholic patients. Using aminopyrine breath test results, the patients were stratified into group 1 (aminopyrine breath test > 2%), group 2 (1% < or = aminopyrine breath test < 2%) and group 3 (aminopyrine breath test < 1%). Survival rates at 4 years were 68% in group 1, 35% in group 2 and 17% in group 3. Using the Child-Turcotte-Pugh score, survival rates at 4 years were 67% in Child-Turcotte-Pugh class A, 40% in class B and 7% in class C. To assess the value of aminopyrine breath test as an adjunct to Child-Turcotte-Pugh score in prognostic evaluation of patients with cirrhosis, two approaches have been used: a regression analysis using Cox's proportional hazard model by including the Child-Turcotte-Pugh score and aminopyrine breath test value, and the log-rank test to assess the prognostic value of aminopyrine breath test in each Child-Turcotte-Pugh class separately. The regression analysis showed that both parameters, the Child-Turcotte-Pugh score and the aminopyrine breath test results, were accepted in the model, suggesting that the aminopyrine breath test was still significantly related to survival once the Child-Turcotte-Pugh score had been entered into the model. Analysis of the prognostic value of the aminopyrine breath test in each Child-Turcotte-Pugh class separately indicated, however, that the contribution was negligible in the Child-Turcotte-Pugh class C.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
421. [The use of lymphocyte cultures for the investigation of drug biotransformation]
- Author
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A, Langner, M F, Melzig, S, Kempa, and A, Krause
- Subjects
Male ,Cell Survival ,Codeine ,Morpholines ,Rats ,Mice ,Pharmaceutical Preparations ,Nitrobenzoates ,Tumor Cells, Cultured ,Animals ,Anticonvulsants ,Pyrroles ,Lymphocytes ,Rats, Wistar ,Aminopyrine ,Multiple Myeloma ,Biotransformation ,Cells, Cultured - Abstract
In the present paper the rat lymphocytes and mouse myeloma cell culture are developed as in vitro test systems and used for the investigation on the biotransformation of drugs. The rat lymphocyte culture was established as a suspension culture after the isolation of the cells from the spleen of male wistar rats by mechanical disaggregation and density gradient centrifugation with a yield of 10(7) cells per spleen and a viability of 80%. The addition of the mitogens PHA and Con A to the culture stimulated the proliferation of the lymphocytes leading to a doubling of the number of cells comparing with control cultures. Myeloma cells are a permanent cell line of B-lymphocytes. The cultivation was carried out as stationary suspension. The marked proliferation of the cells could be increased by addition of Con A. The biochemical properties of both kinds of cells are qualitatively comparable. Cytochrome P-450 mediated demethylase activities could be detected, which were 5-10 fold higher in myeloma cells. The pretreatment with the enzyme inductors phenobarbitone and 3-methylcholanthrene as well as the addition of the mitogens PHA and Con A increased these turnover rates. Reductive and conjugating activities were not present in the cultures. The established and characterized in vitro systems were applied for the investigation on the biotransformation of 4 potential drugs. The cardiac effective Trapidil (Rocornal) derivative AR 12463 (5-piperidino-7-[N-pentyl-N-(beta-hydroxyethyl)]- amino-s-triazolo[1,5-a]pyrimidine) is transformed in lymphocyte and myeloma cell cultures in two compounds. These substances revealed as the hydroxypentyl- and the hydroxypyrimidine derivative.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
422. Relationship between oxidative hepatic metabolism, urinary sodium excretion and sympathetic nerve activity in experimental cirrhosis in the rat
- Author
-
G, Wensing, R, Sabra, and R A, Branch
- Subjects
Male ,Sympathetic Nervous System ,Natriuresis ,Blood Pressure ,Water-Electrolyte Balance ,Liver Cirrhosis, Experimental ,Rats ,Rats, Sprague-Dawley ,Norepinephrine ,Breath Tests ,Liver ,Phenobarbital ,Animals ,Aminopyrine ,Carbon Tetrachloride ,Oxidation-Reduction ,Glomerular Filtration Rate - Abstract
This study investigated the relationship between changes in renal sympathetic activity as assessed by renal norepinephrine spill-over and the onset of renal sodium retention in the phenobarbital/carbon tetrachloride model of experimental cirrhosis in rats. In this model, sodium retention occurs when hepatic function, assessed by the aminopyrine breath test (ABT), falls below a critical threshold. Three groups of rats, studied on a constant salt diet, included a group with cirrhosis and sodium retention, a group with cirrhosis of similar duration and no sodium retention and a time-control phenobarbitaltreated group. ABT, renal plasma flow (RPF), glomerular filtration rate (GFR) and mean arterial pressure (MAP) were measured at the time of catecholamine sampling in anesthetized rats. Cirrhosis was associated with reductions in MAP, no change in RPF and GFR, and an ABT below the threshold in rats with sodium retention. In contrast, rats without sodium retention had liver function above the threshold. Renal norepinephrine spill-over increased continuously from controls to non-sodium retaining and sodium retaining animals. The difference between sodium retaining animals and controls was significant. Norepinephrine spill-over correlated to ABT and MAP but not urinary salt excretion. The data suggest that, under these experimental conditions, increased sympathetic activity may contribute to the onset of sodium retention. A plausible explanation for the continuous increase is that catecholamines are released as a compensatory mechanism in response to a primary yet undefined vasodilator.
- Published
- 1995
423. Gaseous nitrogen dioxide increases the endogenous synthesis of carcinogenic N-nitrosodimethylamine in animals
- Author
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Bl, Rubenchik, Aa, Glavin, Pm, Galenko, Aa, Kilkichko, Io, Oleinick, and Kv, Artemov
- Subjects
Male ,Sodium Nitrite ,Anti-Inflammatory Agents, Non-Steroidal ,Nitrogen Dioxide ,Administration, Oral ,Alanine Transaminase ,Dimethylnitrosamine ,Rats ,Mice, Inbred C57BL ,Drug Combinations ,Mice ,Liver ,Administration, Inhalation ,Carcinogens ,Animals ,Aminopyrine ,Biomarkers ,DNA Damage ,Glutathione Transferase ,Mutagens - Abstract
Inhalation of nitrogen dioxide (NO2) by mice administered orally amidopyrine (AP) and sodium nitrite resulted in increased biosynthesis of N-nitrosodimethylamine (NDMA), as determined by analysis using gas chromatography with thermal energy analyzer detector. These results were also confirmed indirectly in chronic experiments on rats using the system of biomarkers of NDMA formation (single-stranded DNA liver damages, alanine-aminotransferase, glutathione-S-transferase, and liver S9 fraction activity). The inhibition of NDMA metabolism by 4-methylpyrazol (4-MP) administration increases the sensitivity of NDMA biosynthesis assay in frozen whole-mouse powder. The results confirm that NO2 can serve as the precursor of nitrosamines.
- Published
- 1995
424. Significance of aminopyrine breath test as a parameter of hepatic functional reserve in 40% partial hepatectomy of rats with CCl4-induced liver injury
- Author
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Satoru Anbiru, Satoshi Ohtawa, Takashi Kaiho, Akira Togawa, Takenori Sugasawa, Masayuki Ohtsuka, Norio Yasuda, Kijuro Takanishi, Motoki Nagai, Eiji Gohchi, M. Miyazaki, Nobuyuki Nakajima, Akira Ogata, Hiroshi Itoh, Shinichi Hayashi, and Katsuhiko Ando
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,CCL4 ,Partial hepatectomy ,Liver Cirrhosis, Experimental ,Gastroenterology ,chemistry.chemical_compound ,Liver Function Tests ,Internal medicine ,medicine ,Animals ,Hepatectomy ,Aspartate Aminotransferases ,Rats, Wistar ,HEPATIC PROTEIN ,Aminopyrine ,Carbon Tetrachloride ,Liver injury ,Breath test ,medicine.diagnostic_test ,business.industry ,Surgical mortality ,Alanine Transaminase ,General Medicine ,medicine.disease ,Rats ,chemistry ,Breath Tests ,Liver ,Protein Biosynthesis ,Carbon tetrachloride ,business - Abstract
Rats with CCl4-induced liver injury underwent partial (40%) hepatectomy. The [14C]aminopyrine breath test (ABT) values in rats with CCl4-induced liver injury were reduced by 34% compared with those in rats with normal liver. Preoperative ABT values clearly discriminated between survivors and those that died following 40% partial hepatectomy in rats CCl4-induced liver injury (P
- Published
- 1995
425. In vivo metabolism of aminopyrine by the larvae of the helminth Heligmosomoides polygyrus
- Author
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J.L. Brazier, Dominique Kerboeuf, Denis Soubieux, Jean-Louis Rivière, and Roger Guilluy
- Subjects
Chromatography, Gas ,Cytochrome ,Mass Spectrometry ,Mice ,In vivo ,parasitic diseases ,medicine ,Parasite hosting ,Helminths ,Animals ,Dimethyl Sulfoxide ,Anthelmintic ,Aminopyrine ,Adrenergic alpha-Antagonists ,Larva ,Nematospiroides dubius ,General Veterinary ,biology ,Imidazoles ,In vivo metabolism ,General Medicine ,biology.organism_classification ,Infectious Diseases ,Biochemistry ,Dealkylation ,Insect Science ,biology.protein ,Parasitology ,Heligmosomoides polygyrus ,medicine.drug - Abstract
The in vivo N-dealkylation of [13C-2]-labeled aminopyrine by the L1-L2 larvae of Heligmosomoides polygyrus was demonstrated by the use of a sensitive gas chromatography-mass spectrometry method. This is the first evidence for the possible existence of a cytochrome P-450-dependent activity in helminths.
- Published
- 1995
426. Pillar height dependent formation of unprecedented Pd8 molecular swing and Pd6 molecular boat via multicomponent self-assembly
- Author
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Sankarasekaran Shanmugaraju, Sachin A. Joshi, Yogesh P. Patil, Dipak Samanta, Munirathinam Nethaji, and Partha Sarathi Mukherjee
- Subjects
Diffraction ,Chemistry ,Stereochemistry ,Imidazoles ,Molecular Conformation ,Metals and Alloys ,Pillar ,General Chemistry ,Swing ,Acceptor ,Fluorescence ,Catalysis ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Crystallography ,Isomerism ,Materials Chemistry ,Ceramics and Composites ,Titration ,Fullerenes ,Self-assembly ,Aminopyrine ,Palladium - Abstract
Three-component self-assembly of a cis-blocked 90 degrees Pd(II) acceptor with a mixture of a tetraimidazole and a linear dipyridyl donor self-discriminated into unusual Pd-8 molecular swing (1) and Pd-6 molecular boat (2), which are characterized by single-crystal X-ray diffraction analysis; their ability to bind C-60 in solution is established by fluorescence titration.
- Published
- 2012
427. Effect of Helicobacter pylori on dbc-AMP stimulated acid secretion by human parietal cells
- Author
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H, Jablonowski, K J, Hengels, N, Krämer, G, Geis, W, Opferkuch, and G, Strohmeyer
- Subjects
Campylobacter jejuni ,Gastric Acid ,Helicobacter pylori ,Parietal Cells, Gastric ,Biopsy ,Colony Count, Microbial ,Cyclic AMP ,Humans ,Cardia ,Carbon Radioisotopes ,Aminopyrine ,Omeprazole - Abstract
This study examines the effect of different H.p. strains (A-D) on dbc-AMP stimulated acid secretion by human parietal cells in vitro. H.p. strains A and D reduced acid secretion dose-dependently between 20 and 80%. In contrast, H.p. strains B and C had little or no effect. We conclude that H.p. strains vary in their ability to suppress acid secretion, and that the site of inhibition lies beyond the c-AMP level, possibly involving the K+H(+)-ATPase of the parietal cell. Interference with acid secretion may facilitate H.p. colonization of the stomach and may prove to be an important pathogenetic factor.
- Published
- 1994
428. Multiple actions of epidermal growth factor and TGF-alpha on rabbit gastric parietal cell function
- Author
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C. S. Chew, K. Nakamura, and A. C. Petropoulos
- Subjects
Male ,medicine.medical_specialty ,TGF alpha ,Time Factors ,Physiology ,Genistein ,Biology ,Dinoprostone ,chemistry.chemical_compound ,Parietal Cells, Gastric ,Epidermal growth factor ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Virulence Factors, Bordetella ,Tyrosine ,Phosphorylation ,Protein kinase A ,Aminopyrine ,Hepatology ,Dose-Response Relationship, Drug ,Epidermal Growth Factor ,Kinase ,Gastroenterology ,Protein-Tyrosine Kinases ,Transforming Growth Factor alpha ,Phosphoproteins ,Endocrinology ,chemistry ,Pertussis Toxin ,Rabbits ,Tyrosine kinase - Abstract
Parietal cells in primary culture and freshly isolated parietal cells were used to compare acute and chronic effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on acid-secretory related activity, measured as accumulation of the weak base, [14C]aminopyrine (AP). EGF and TGF-alpha chronically enhanced basal and agonist-stimulated AP accumulation (mean effective concentration 0.6-0.8 nM) but acutely inhibited responses to histamine and carbachol (half-maximal inhibitory concentration approximately 4 nM). Pertussis toxin (250 ng/ml, 4 h) suppressed acute EGF inhibition of histamine-stimulated AP accumulation but not the chronic enhancement. A subclass of tyrosine kinase inhibitors suppressed chronic EGF effects (genistein > tyrphostin B56 >>> tyrphostin B42), whereas tyrphostin A25, lavendustin A, and the inactive genistein analogue, daidzein, had no significant effect. In contrast, histamine-stimulated AP accumulation was acutely potentiated by genistein, daidzein, and tyrphostin B42, but not tyrphostin B56. Reduced phosphorylation of a 44- to 45-kDa protein with an isoelectric point of approximately 7 [phosphoprotein (pp) 44] was correlated with chronic inhibition but not with acute potentiation by specific tyrosine kinase inhibitors. Preliminary data indicate that pp44 is a member of the mitogen-activated protein kinase family of tyrosine/threonine kinases (also known as extracellular signal-related kinases). We propose that 1) EGF and/or TGF-alpha modulates parietal cell function by multiple signaling pathways, 2) a soluble tyrosine kinase may be involved in the mediation of the chronic effects of EGF, and 3) acute potentiation of histamine-stimulated AP accumulation by certain tyrosine kinase inhibitors and daidzein is probably not mediated by receptor-associated tyrosine kinases.
- Published
- 1994
429. Exendin-4 and exendin-(9-39)NH2: agonist and antagonist, respectively, at the rat parietal cell receptor for glucagon-like peptide-1-(7-36)NH2
- Author
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Jens J. Holst, Meinhard Classen, John Eng, Kerstin Dehne, Wolfgang Schepp, Thomas Riedel, Johanna Schmidtler, Volker Schusdziarra, and Jean-Pierre Raufman
- Subjects
endocrine system ,medicine.medical_specialty ,medicine.drug_class ,Glucagon-Like Peptides ,Stimulation ,Peptide ,In Vitro Techniques ,complex mixtures ,Binding, Competitive ,Gastric Acid ,chemistry.chemical_compound ,fluids and secretions ,Parietal Cells, Gastric ,Glucagon-Like Peptide 1 ,Internal medicine ,medicine ,Cyclic AMP ,Receptors, Glucagon ,Animals ,Rats, Wistar ,Receptor ,Aminopyrine ,Parietal cell ,Pharmacology ,chemistry.chemical_classification ,Venoms ,digestive, oral, and skin physiology ,Cell Membrane ,Radioimmunoassay ,Lizards ,Receptor antagonist ,Glucagon ,Adenosine ,Peptide Fragments ,Rats ,medicine.anatomical_structure ,Endocrinology ,Cross-Linking Reagents ,chemistry ,Exenatide ,Female ,Peptides ,hormones, hormone substitutes, and hormone antagonists ,Histamine ,medicine.drug - Abstract
Exendin-4 is a novel peptide from Heloderma suspectum venom which is 53% homologous with glucagon-like peptide-1 GLP-1-(7-36)NH2, a stimulant of cAMP-dependent H+ production in rat parietal cells. It was the aim of the present study to determine whether this effect of GLP-1-(7-36)NH2 is shared by exendin-4, and whether the responses to either peptide are blocked by exendin-(9-39)NH2, a competitive specific exendin receptor antagonist. In enriched rat parietal cells H+ production was measured indirectly by [14C]aminopyrine accumulation. cAMP production was determined by radioimmunoassay. [125I]GLP-1-(7-36)NH2 was prepared using chloramine T followed by high pressure liquid chromatography (HPLC) purification. Exendin-4 (10(-12) - 10(-8) M) stimulated [14C]aminopyrine accumulation in a concentration-dependent manner (EC50 = 7.6 x 10(-11) M). At the maximally effective concentration (10(-9) M) exendin-4 was as effective as GLP-1-(7-36)NH2 reaching 70-80% of the response to 10(-4) M histamine. Likewise, exendin-4 (10(-11) - 10(-7) M) stimulated parietal cell cAMP production up to 2.8-fold. Maximal stimulation by exendin-4 of [14C]aminopyrine accumulation was not affected by ranitidine (10(-4) M), but was concentration-dependently reduced by exendin-(9-39)NH2 (10(-11) - 10(-7) M). At the maximal concentration, exendin-(9-39)NH2 completely abolished the responses to 10(-9) M exendin-4 and to 10(-9) M GLP-1-(7-36)NH2 while not altering stimulation by 10(-4) M histamine. Binding of [125I]GLP-1-(7-36)NH2 to enriched parietal cells was displaced by exendin-4 (Ki = 4.6 x 10(-10) M) as well as by exendin-(9-39)NH2 (Ki = 4.0 x 10(-9) M).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
430. A device for automatic measurement of writhing and its application to the assessment of analgesic agents
- Author
-
Ken-Ichi Adachi
- Subjects
Male ,Materials science ,Wheatstone bridge ,Time Factors ,Comparator ,Acoustics ,Injections, Subcutaneous ,Transducers ,Pain ,Acetates ,Toxicology ,Analgesic agents ,law.invention ,Mefenamic Acid ,Mice ,law ,Caffeine ,Animals ,Aminopyrine ,Strain gauge ,Acetic Acid ,Pain Measurement ,Pharmacology ,Inflammation ,Analgesics ,Behavior, Animal ,Dose-Response Relationship, Drug ,Morphine ,Tension (physics) ,Detector ,Electric Stimulation ,Multivibrator ,Disease Models, Animal ,Transducer ,Drug Evaluation - Abstract
A device was developed for automatically measuring writhing in mice so as to be applied to the assessment of analgesic agents. The device was composed of a specially designed container equipped with a detector, namely, a mechanoelectro transducer for writhing. The detector was made up of units of a string, two plates, and two strain gauges. In the unit, each end of the string was connected to either of the plates to which either of the strain gauges was attached. The change in tension of the string due to writhing was converted into the mechanical strain of the plates and then the resistance change of the strain gauges. The resistance change was amplified by a Wheatstone bridge circuit that was connected to a differential amplifier, a high-pass filter, comparator(s), and a monostable multivibrator to obtain the electrical signal for writhing. Using this device, writhing was continuously measured, and evaluation of various types of analgesic agents was performed. The result suggests that this device has sufficient accuracy both for the detection of writhing and the evaluation of analgesics. It has the advantage of automatic measurement of writhing in contrast to the conventional visual observation method.
- Published
- 1994
431. Evaluation of hepatocellular function by way of receptor-mediated uptake of a technetium-99m-labeled asialoglycoprotein analog
- Author
-
Walter Trudeau, Dusan P. Hutak, Robert C. Stadalnik, David R. Vera, and Neville R. Pimstone
- Subjects
Indocyanine Green ,medicine.medical_specialty ,Cirrhosis ,Receptors, Cell Surface ,Asialoglycoprotein Receptor ,Gastroenterology ,Sensitivity and Specificity ,Liver disease ,Primary biliary cirrhosis ,Liver Function Tests ,Predictive Value of Tests ,Internal medicine ,Albumins ,medicine ,Humans ,Carbon Radioisotopes ,Aminopyrine ,Radionuclide Imaging ,Breath test ,Liver injury ,Hepatology ,medicine.diagnostic_test ,business.industry ,Liver Cirrhosis, Biliary ,Liver Diseases ,Organotechnetium Compounds ,medicine.disease ,Breath Tests ,Liver ,Liver biopsy ,Chronic Disease ,Liver function ,business - Abstract
We have developed a quantitative functional imaging study of the liver using a radiolabeled asialoglycoprotein analog, Tc-galactosyl-neoglycoalbumin. Heart and liver time-activity data can be transformed by automated kinetic analysis into asialoglycoprotein hepatocyte receptor concentration. Twenty-eight healthy controls, 46 patients with noncholestatic chronic liver injury and 11 patients with primary biliary cirrhosis were studied. Liver function was also assessed by Pugh modified-Child-Turcotte criteria, 14C-aminopyrine breath test and indocyanine green clearance (24 patients). Results: (a) In normal controls with a Child-Turcotte criteria score of 5, receptor concentration ranged from 0.63 to 1.19 μmol/L, with a mean 0.83 ± 2 S.D. 0.06 μmol/L, which was significantly higher (p < 0.001) than that of the patient group (mean receptor concentration = 0.44 ± 2 S.D. 0.04 μmol/L). In cirrhotic patients with Child-Turcotte criteria score of 5, the mean receptor concentration was 0.60 ± 2 S.D. 0.07 μmol/L, which was significantly lower than controls (p < 0.01). In end-stage cirrhosis (Child-Turcotte criteria score 11 to 15), a group in which patients died or required orthotopic liver transplantation within 1 yr, the mean receptor concentration was 0.35 ± 2 S.D. to 0.07 μmol/L. The sensitivity and specificity for receptor concentration in relation to liver disease, with values above 0.65 μmol/L being normal, were 0.96 and 0.88, respectively. Receptor concentration correlated well with Child-Turcotte criteria score (r = 0.78, p =
- Published
- 1994
432. Oxygen radical formation by the cytochrome P450 system as a cellular mechanism for cyclosporine toxicity
- Author
-
F, Serino, J, Grevel, K L, Napoli, B D, Kahan, and H W, Strobel
- Subjects
Male ,Proadifen ,Free Radical Scavengers ,Rats ,Rats, Sprague-Dawley ,Kinetics ,Chloramphenicol ,Ketoconazole ,Cytochrome P-450 Enzyme System ,Enzyme Induction ,Phenobarbital ,Cyclosporine ,Microsomes, Liver ,Animals ,Lipid Peroxidation ,Aminopyrine ,NADP - Published
- 1994
433. Functional and structural changes of isolated rat parietal cells during membrane potential modulation
- Author
-
J, Ostrowski, D, Jarosz, W, Zych, and K, Wojciechowski
- Subjects
4-Nitrophenylphosphatase ,Carbonyl Cyanide m-Chlorophenyl Hydrazone ,H(+)-K(+)-Exchanging ATPase ,Parietal Cells, Gastric ,Animals ,Aminopyrine ,Membrane Potentials ,Rats - Abstract
The present experiments were undertaken to extent our earlier observations (J Physiol Pharmacol 1991, 42, 367-79) relating membrane potential with membrane recycling of parietal cells. Studies were performed in vitro using gastric glands that were isolated through the use of rat stomachs transformed into "everted sacs" and filled with hyperosmolar NaCl-EDTA solution. Acid production was indirectly determined by accumulation of 14C-aminopyrine (AP) and its translocation by measurement of acridine orange fluorescence. H+/K(+)-ATPase activity was assayed by measurement of K(+)-stimulated p-nitrophenylphosphatase (pNPPase) of the proton pump. Morphologic state of parietal cells in relation to their functional activity was observed using electron microscopy. Changes in the membrane potential were obtained by the treatment of gastric glands with protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) in the incubation media of different pH. CCCP caused time-dependent decrease in AP accumulation by parietal cells from the medium of pH 6.6 but not that of pH 7.8. pNPPase activity increased in aplical and decreased in tubulovesical membrances prepared from CCCP treated glands which were incubated in the medium being more acidic than cell cytoplasm. Electron microscopic assessment showed morphological transformation of resting parietal cells treated with CCCP in pH 6.6 from nonsecreting to secreting state. CCCP acting in acidic incubation medium also caused the decrease in acridine orange fluorescence in the cytoplasm of parietal cells with some temporary increase of its fluorescence in the lumen o gastric glands. These findings support our hypothesis that changes in parietal cell membrane potential by protonophore CCCP may translocate HCl from tubulovesicles to secretory canaliculi. While the above explanation is suggestive, the exact mechanisms controlling a membrane recycling during the secretory response of parietal cells in vitro remain to be elucidated.
- Published
- 1994
434. The effect of recombinant cytokines on [14C]-aminopyrine accumulation by isolated canine parietal cells
- Author
-
D J, Nompleggi, M, Beinborn, A, Roy, and M M, Wolfe
- Subjects
Tumor Necrosis Factor-alpha ,Indomethacin ,Histamine Antagonists ,Recombinant Proteins ,Dogs ,Parietal Cells, Gastric ,1-Methyl-3-isobutylxanthine ,Animals ,Humans ,Carbachol ,Carbon Radioisotopes ,Aminopyrine ,Cells, Cultured ,Interleukin-1 - Abstract
Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been shown to inhibit basal and pentagastrin-stimulated gastric secretion in rats and histamine-stimulated secretion in dogs. IL-1 also reduces the severity of ethanol and stress-induced gastroduodenal damage. The aim of this study was to examine the effects of human recombinant IL-1 alpha and TNF-alpha on enzymatically dispersed and enriched (90%) parietal cells stimulated with histamine, histamine plus 3-isobutyl-1-methylxanthine (IMX) or carbachol (all 10(-5) M). Acid secretion was assessed indirectly by quantitating [14C]-aminopyrine (AP) accumulation. IL-1 alpha (500 and 1000 ng/ml) inhibited histamine-stimulated AP uptake by 53% and 60% respectively, and it inhibited IL-1 alpha (1500 ng/ml) by 69%. IL-1 alpha (500 and 1000 ng/ml) inhibited histamine plus IMX-stimulated AP uptake by 36% and 34%, respectively. IL-1 alpha (500 ng/ml) also inhibited carbachol-stimulated AP accumulation. TNF-alpha (100 and 250 ng/ml) inhibited histamine-stimulated AP accumulation by 38% and 36%, respectively. TNF-alpha also significantly inhibited histamine/IMX- and carbachol-stimulated AP uptake (Por = .01). Indomethacin did not affect IL-1 alpha-induced inhibition. These results show that IL-1 alpha and TNF-alpha inhibit histamine- and carbachol-stimulated isolated parietal cell secretion and that, for IL-1 alpha, this effect does not depend on mucosal prostaglandin synthesis.
- Published
- 1994
435. Effects of ascorbic acid on iproniazid-induced hepatitis in phenobarbital-treated rats
- Author
-
Rie Bandou, Harumi Maeda, Hiroshi Kiwada, Tsuyoshi Goromaru, and Yoko Matsuki
- Subjects
Male ,medicine.medical_specialty ,Chromatography, Gas ,Metabolite ,Pharmaceutical Science ,Ascorbic Acid ,Isotope dilution ,Iproniazid ,chemistry.chemical_compound ,Liver Function Tests ,Internal medicine ,Medicine ,Animals ,Aspartate Aminotransferases ,Rats, Wistar ,Aminopyrine ,Pharmacology ,business.industry ,Alanine Transaminase ,General Medicine ,Ascorbic acid ,Rats ,Kinetics ,Endocrinology ,Hydrazines ,chemistry ,Liver ,Aminophenazone ,Phenobarbital ,Toxicity ,Liver function ,Chemical and Drug Induced Liver Injury ,business ,medicine.drug - Abstract
The effects of ascorbic acid (AA) on hepatic injury induced by iproniazid (IPN) in phenobarbital-treated rats were investigated by the evaluation of hepatic function using the clearance of aminopyrine (AM). Either IPN or isopropylhydrazine (IP-Hy), a potent toxic metabolite of IPN, were administered as a pretreatment to rats with or without AA. After i.v. injection of AM, the blood concentration of AM was determined by capillary gas chromatography by isotope dilution analysis using deuterium-labeled AM (AM-d 9 ) as the internal standard. The kinetic parameters of AM, V d , k el and total body clearance, were estimated from the time course of blood concentration. Pretreatment with MN with AA led to a marked increase in the k el and in the clearance compared with pretreatment using IPN alone. A significant increase in the k el and the clearance was also found in the case of combined pretreatment using IP-Hy with AA. The effects of AA on the hepatic injury induced by IPN were studied according to its histological aspects. In the specimens obtained following the administration of IPN or IP-Hy with AA, the degree of cell necrosis was remarkably lowed both quantitatively and qualitatively. The present results clearly demonstrate that AA was effective in reducing IPN-induced hepatitis
- Published
- 1994
436. The aminopyrine breath test
- Author
-
F, Perri, M, Pastore, V, Annese, and A, Andriulli
- Subjects
Breath Tests ,Cytochrome P-450 Enzyme System ,Liver ,Liver Function Tests ,Liver Diseases ,Microsomes, Liver ,Humans ,Carbon Radioisotopes ,Aminopyrine ,Prognosis - Abstract
The metabolic basis and clinical application of the aminopyrine breath test (ABT) as a measure of liver function is reviewed in this article. Several papers have been published in the 20 years that have elapsed since the test was validated in man by Hepner and Vesell. Nevertheless, even if the aminopyrine breath test has been shown to be a non-invasive, reliable and semiquantitative liver function test with diagnostic and prognostic accuracy, it is not yet extensively used in clinical practice, probably because it is not widely known to clinicians. The aminopyrine breath test, like other newer tests (phenacetin, caffeine and erythromycin breath tests), allows the effects of drugs on hepatic cytochrome P-450 to be explored both in normal subjects and in liver patients. This interesting field of application is sure to expand the appeal of the aminopyrine breath test in the future.
- Published
- 1994
437. Effects of Helicobacter pylori on histamine and carbachol stimulated acid secretion by human parietal cells
- Author
-
Opferkuch W, G Geis, N Kraemer, Georg Strohmeyer, K J Hengels, and H. Jablonowski
- Subjects
medicine.medical_specialty ,Carbachol ,Spirillaceae ,In Vitro Techniques ,Helicobacter Infections ,Gastric Acid ,chemistry.chemical_compound ,Parietal Cells, Gastric ,Internal medicine ,medicine ,Gastric mucosa ,Humans ,Secretion ,Aminopyrine ,Omeprazole ,biology ,Dose-Response Relationship, Drug ,Helicobacter pylori ,Stomach ,Gastroenterology ,biology.organism_classification ,bacterial infections and mycoses ,Molecular biology ,Stimulation, Chemical ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Histamine ,medicine.drug ,Research Article - Abstract
Helicobacter pylori (H pylori) infection is associated with hypo, normal, and hypersecretory disorders of the gastric mucosa. Pathophysiological pathways by which H pylori interacts with acid secretion are still unclear. The effects of H pylori on (14C) aminopyrine uptake by human parietal cells were examined as an indirect assay for acid secretion. Isolated oxyntic glands were stimulated with submaximal concentrations of histamine or carbachol and incubated with sonicates of different H pylori strains. Omeprazole and sonicates of Campylobacter jejuni served as positive and negative controls, respectively. Two of four H pylori strains reduced hydrochloric acid sequestration within the parietal cells significantly and in a dose dependent manner in up to 80%. Interaction with acid secretion may therefore constitute a factor contributing to a distinct pathogenicity of H pylori strains.
- Published
- 1994
438. Short report: interferon-alpha decreases 14C-aminopyrine breath test values in patients with chronic hepatitis C
- Author
-
Yves Horsmans, Réginald Brenard, and André Geubel
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Alpha interferon ,Gastroenterology ,Drug Administration Schedule ,chemistry.chemical_compound ,Cytochrome P-450 Enzyme System ,Internal medicine ,medicine ,Cytochrome P-450 Enzyme Inhibitors ,Humans ,Pharmacology (medical) ,Aminopyrine ,Interferon alfa ,Aged ,Breath test ,Chemotherapy ,Hepatology ,biology ,medicine.diagnostic_test ,business.industry ,Cytochrome P450 ,Interferon-alpha ,Middle Aged ,Hepatitis C ,Surgery ,chemistry ,Breath Tests ,Aminophenazone ,Chronic Disease ,biology.protein ,Microsome ,Female ,Liver function ,business ,medicine.drug ,Aminopyrine N-Demethylase - Abstract
Objective: To investigate the effect of interferon-alpha on cytochrome P-450 dependent microsomal function. Methods: The C-14-aminopyrine breath test was performed before, during and after a standard dose of interferon-alpha (3 000 000 units three times per week) was administered for at least six months (nine patients with chronic hepatitis C). Results: Mean aminopyrine breath test values obtained during therapy were significantly lower than either pre- or post-treatment, the degree of reduction varying widely between individuals. Pre- and post-treatment aminopyrine breath test values did not differ significantly. Conclusion: Interferon therapy is associated with a significant and transient inhibition of cytochrome P-450 activity, which should be taken into account when prescribing concurrent therapy with drugs metabolized by this pathway.
- Published
- 1994
439. Stimulation of rat parietal cell function by histamine and GLP-1-(7-36) amide is mediated by Gs alpha
- Author
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W. Rosenthal, Wolfgang Schepp, Meinhard Classen, Stefan Offermanns, Kerstin Dehne, and Johanna Schmidtler
- Subjects
medicine.medical_specialty ,Cholera Toxin ,Physiology ,G protein ,Glucagon-Like Peptides ,Cell Separation ,Biology ,medicine.disease_cause ,Cyclase ,chemistry.chemical_compound ,Histamine H2 receptor ,Parietal Cells, Gastric ,GTP-Binding Proteins ,Glucagon-Like Peptide 1 ,Physiology (medical) ,Internal medicine ,medicine ,Cyclic AMP ,Animals ,Rats, Wistar ,Aminopyrine ,Cells, Cultured ,Parietal cell ,Forskolin ,Hepatology ,Dose-Response Relationship, Drug ,Cholera toxin ,Cell Membrane ,Colforsin ,Gastroenterology ,Glucagon ,Peptide Fragments ,Rats ,Adenosine Diphosphate ,Molecular Weight ,Kinetics ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Electrophoresis, Polyacrylamide Gel ,Female ,Cyclase activity ,Histamine ,Adenylyl Cyclases - Abstract
It was the aim of the present study to determine in rat parietal cells whether Gs alpha, the stimulatory subunit of adenylate cyclase, mediates adenosine 3',5'-cyclic monophosphate (cAMP)-dependent parietal cell function in response to histamine and glucagon-like peptide 1 (GLP-1)-(7-36) amide. Cytoplasmic membrane from enriched (83 +/- 5%) rat parietal cells were incubated for 30 min with 30 microCi/ml [32P]NAD+ and 40 micrograms/ml preactivated cholera toxin (CT), a pharmacological tool for activation of Gs alpha. Subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography revealed [32P]ADP ribosylation of Gs alpha represented by three proteins with molecular masses ranging from 42 to 45 kDa. In intact parietal cells, CT (10(-12)-10(-8) M) caused marked stimulation of [14C]aminopyrine accumulation and cAMP production confirming the functional importance of Gs alpha in regulation of H+ production. Identical membrane preparations were preincubated (2 h, 4 degrees C) in parallel with and without RM/1, a rabbit polyclonal anti-Gs alpha-antibody. Subsequently, adenylate cyclase was stimulated by histamine, GLP-1-(7-36) amide, CT, or forskolin. At a 1:10 dilution, the antiserum completely abolished adenylate cyclase activity in response to maximal concentrations of histamine, GLP-1-(7-36) amide, and CT while reducing forskolin stimulation by only 22.0 +/- 4.9%. At 1:50, RM/1 reduced responses to histamine, GLP-1-(7-36) amide and CT by 20-30% but failed to inhibit forskolin-stimulated enzyme activity. At 1:100, the antiserum was ineffective versus all stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
440. Sex-related differences in the expression of cytochrome P450 in hamsters: cDNA cloning and examination of the expression of three distinct CYP2C cDNAs
- Author
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T, Sakuma, K, Masaki, S, Itoh, T, Yokoi, and T, Kamataki
- Subjects
Male ,Sex Characteristics ,DNA, Complementary ,Base Sequence ,Mesocricetus ,Tolbutamide ,Molecular Sequence Data ,Benzphetamine ,Saccharomyces cerevisiae ,Hydroxylation ,Cytochrome P-450 Enzyme System ,Cricetinae ,Microsomes, Liver ,Animals ,Female ,Cloning, Molecular ,Aminopyrine ,Cytochrome P450 Family 2 ,Oligonucleotide Probes ,Sequence Alignment - Abstract
Sex-related differences in the expression of cytochrome P450 isozymes in hamsters were investigated. Three distinct cDNA clones (assigned as CYP2C25, CYP2C26, and CYP2C27) were isolated from liver cDNA libraries from male and female hamsters, using rat CYP2C11 cDNA as a probe. Sequence analysis revealed that these three forms were very similar to each other (90% identity of nucleotide sequences) and belong to the CYP2C gene subfamily. The CYP2C25, CYP2C26, and CYP2C27 cDNA clones consisted of an open reading frame encoding 490 amino acids. CYP2C25, CYP2C26, and CYP2C27 proteins expressed in Saccharomyces cerevisiae catalyzed the hydroxylation of tolbutamide and the N-demethylation of aminopyrine and benzphetamine. Only CYP2C25 showed testosterone hydroxylase (16 beta) activity. Northern blot analyses with specific oligonucleotide probes demonstrated that expression of CYP2C27 was male specific and male predominant in kidneys and livers, respectively. No sex-related difference was observed in the expression of CYP2C25 and CYP2C26. These results support our previous findings that sex-related differences in the expression of liver microsomal cytochromes P450 occur in hamsters.
- Published
- 1994
441. Secretagogue-induced [14C]aminopyrine uptake in isolated equine parietal cells
- Author
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Martha Campbell-Thompson
- Subjects
Male ,Time Factors ,Dose-Response Relationship, Drug ,Swine ,Biological Transport ,Rats ,Kinetics ,Parietal Cells, Gastric ,Species Specificity ,Gastric Mucosa ,1-Methyl-3-isobutylxanthine ,Animals ,Humans ,Carbachol ,Female ,Pentagastrin ,Carbon Radioisotopes ,Horses ,Aminopyrine ,Cells, Cultured ,Histamine - Abstract
Equine oxyntic mucosal cells were obtained by sequential exposure to pronase and collagenase. Acid production by parietal cells was assessed by uptake of [14C]aminopyrine (AP), a weak base that accumulates in intracellular acidic spaces. Incubation for various times revealed a maximal AP uptake at 10 minutes for histamine and carbachol. Similar secretagogue responses were observed for parietal cells from the mucosal cell preparation or after enrichment by elutriation. Histamine and isobutyl-methylxanthine (IBMX) stimulated AP uptake with a dose-dependent response and maximal effective concentration of 100 microM. Carbachol, 1 to 100 microM, and pentagastrin (PG), 1 to 1,000 nM, were ineffective stimulants of AP uptake. The AP uptake values for 100 microM IBMX, 1 microM carbachol, or 100 nM PG were 77 +/- 6%, 50 +/- 3.2%, and 40 +/- 4.5%, respectively, of that observed with maximal stimulation by 100 microM histamine (mean +/- SEM, n = 4 to 14). Uptake of AP by nonstimulated control cells was 36 +/- 3.6% of maximal histamine stimulation. The AP accumulations during control conditions and after stimulation with 100 microM histamine and IBMX, 1 microM carbachol, or 100 nM PG were 1.18 +/- 0.39, 2.81 +/- 0.85, 1.93 +/- 0.48, 1.44 +/- 0.36, and 1.23 +/- 0.33 pmol of AP/10(5) parietal cells, respectively. Individual histamine dose-response curves were shifted to the right by increasing ranitidine and cimetidine concentrations (0.1 to 50 microM). These results indicate that isolated equine parietal cells are maximally stimulated by histamine and minimally stimulated by carbachol and PG.
- Published
- 1994
442. [Effects of selenium on endogenous synthesis of N-nitrosamines and toxicity of nitrites in rats]
- Author
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E M, Mamaeva, G F, Zhukova, S G, Vlaskina, V P, Deriagina, N A, Golubkina, A B, Sokolov, and S A, Khotimchenko
- Subjects
Male ,Nitrosamines ,Sodium Nitrite ,Biochemical Phenomena ,Animal Feed ,Biochemistry ,Dimethylnitrosamine ,Rats ,Selenium ,Animals ,Rats, Wistar ,Aminopyrine ,Selenomethionine ,Nitrites - Abstract
Male Wistar rats were fed selenium (0.2, 2.9 or 5.5 mg/kg of dry feed) in the form of selenomethionine. They also received for 6 weeks amidopyrine (33 mg/kg b.w.) and/or sodium nitrite (20 mg/kg b.w.) administered intragastrically. The quantitation of endogenously synthetized volatile nitrosamines in the stomach, selenium in the serum, biochemically evaluated nitrite and nitrosamines toxicity revealed an inverse relationship between feed selenium concentrations and the amount of endogenously produced nitrosodimethylamine from equal precursor doses. A protective selenium effect on methemoglobin-producing action of nitrite ions was established. It is shown that introduction of precursors induces increased body need in selenium.
- Published
- 1994
443. Interaction between drugs and pressure-sensitive adhesives in transdermal therapeutic systems
- Author
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T, Kokubo, K, Sugibayashi, and Y, Morimoto
- Subjects
Diffusion ,Acrylates ,Calorimetry, Differential Scanning ,Pharmaceutical Preparations ,Solubility ,Ketoprofen ,Adhesives ,Silicones ,Lidocaine ,Rubber ,Administration, Cutaneous ,Aminopyrine - Abstract
Release experiments with four drugs using representative pressure-sensitive adhesive (PSA) matrices were performed at 37 degrees C, and drug-PSA polymer interaction was determined by the Williams, Landel, and Ferry (WLF) equation. Two acrylic-type [2-ethylhexylacrylate and acrylic acid copolymer (2EHA/AA) or acrylamide copolymer (2EHA/AAm)], one rubber-type (a mixture of high and low molecular weight polyisobutylene), and one silicone-type PSA were used, and dipropylphthalate (PP), aminopyrine (AMP), ketoprofen (KP), and lidocaine (LC) were selected as model drugs because of their molecular size and functional groups. PSA containing acrylic acid (2EHA/AA) strongly interacted with the amide LC, with the tertiary amine AMP, and with the carboxylic acid KP; PSA-containing acrylamide (2EHA/AAm), however, did not interact with LC or AMP, although it markedly interacted with KP. The rubber-type and silicone-type PSAs, composed of no or only a few polar functional groups, did not interact with any of the drugs used in this experiment. Therefore, the diffusion coefficient of the drugs through PSA was influenced by the drug-PSA polymer interaction, and the extent of this interaction can be estimated by the relationship between the drug concentrations in the PSA and their diffusion coefficients.
- Published
- 1994
444. Metabolic function of the liver in caerulein induced acute pancreatitis
- Author
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K, Celiński, Z, Kleinrok, J, Pokora, I, Chibowska, H, Cichoz-Lach, B, Skrzydło-Radomańska, and G, Czechowska
- Subjects
Perfusion ,Liver ,Pancreatitis ,Acute Disease ,Animals ,Rats, Wistar ,Aminopyrine ,Ceruletide ,Rats - Published
- 1994
445. [Nonsteroidal antiinflammatory agents as modulators of glucocorticoid function of receptors]
- Author
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P P, Golikov, N Iu, Nikolaeva, and V V, Marchenko
- Subjects
Male ,Cytosol ,Receptors, Glucocorticoid ,Liver ,Sodium Salicylate ,Dipyrone ,Animals ,Rats, Wistar ,Aminopyrine ,Rats - Abstract
The modulating effect of nonsteroidal antiinflammatory drugs (analgin, amidopyrine, sodium salicylate) on the function of types II and III glucocorticoidal receptors of cytosol in the Wistar rat liver was studied by Scatchard's and Laynuiver-Bark's analyses and dissociation rate constants for steroid-receptor complexes, by using natural and artificial glucocorticoids having a high specific activity. Analgin was not competitive in inhibiting the function of type II glucocorticoid receptors, decreased the association constant, increased the dissociation rate constant and reduced the elimination half-life of the labelled triamcinolone acetonide from the receptor. The density of type III glucocorticoidal receptors was many times increased with analgin. Amidopyrine had no noticeable effect on the function of type II glucocorticoidal receptors, however, repeatedly enhanced the density of type III glucocorticoidal receptors. Sodium salicylate was not competitive in suppressing the function of type II glucocorticoidal receptors and increased the number of sites of binding 3H-corticosterone to type III glucocorticoidal receptors. The latter fact can explain the mechanism of action of these drugs.
- Published
- 1994
446. [C14-aminopyrine breath test and enzymatic liver tests in workers employed by the coke tar distillation department]
- Author
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W, Pokrzywnicki, J, Sroczyński, H, Rudzki, and W, Grzeszczak
- Subjects
Adult ,Male ,Breath Tests ,Liver ,Liver Function Tests ,Chemical Industry ,Occupational Exposure ,Humans ,Female ,Middle Aged ,Aminopyrine ,Coke - Abstract
A group of 400 subjects divided into three sub-groups was examined. Group I consisted of 130 persons employed at the coke tar distillation department. Group II (controls) consisted of 70 persons also employed at the coke plant but free from occupational exposure. Group III was composed of 200 workers employed at the Building Factory. C14-aminopyrine breath test (ABT) was performed in 30 subjects randomly assigned from each group. A standard enzymatic liver test was assessed in all subjects examined. The range of tests performed did not permit to indicate the toxic effect of occupational environment on the liver tissue. Abnormal enzymatic liver test found in all groups could results, among others, from alcohol abuse among those tested. However, it was revealed that aromatic hydrocarbons to which workers of the coke tar distillation department were exposed to, stimulated the activity of the liver microsomal oxygenase assessed by ABT.
- Published
- 1994
447. Rab27b Localizes to the Tubulovesicle Membranes of Gastric Parietal Cells and Regulates Acid Secretion
- Author
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Jo Suda, Curtis T. Okamoto, Lixin Zhu, and Serhan Karvar
- Subjects
Proteomics ,Yellow fluorescent protein ,Recombinant Fusion Proteins ,Blotting, Western ,Biology ,Transfection ,Peptide Mapping ,Gastric Acid ,H(+)-K(+)-Exchanging ATPase ,Parietal Cells, Gastric ,Tandem Mass Spectrometry ,medicine ,Animals ,Humans ,Secretion ,Aminopyrine ,Cells, Cultured ,Parietal cell ,Hepatology ,Gastroenterology ,Intracellular Membranes ,Apical membrane ,Membrane transport ,Immunohistochemistry ,Molecular biology ,Protein Transport ,medicine.anatomical_structure ,Microscopy, Fluorescence ,rab GTP-Binding Proteins ,Mutation ,biology.protein ,Gastric acid ,Rabbits ,Rab - Abstract
Background & Aims Rabs are monomeric guanosine triphosphatases that regulate membrane trafficking and acid secretion in gastric parietal cells. Using a proteomics approach, we identified a new Rab, Rab27b, in tubulovesicle membranes and determined its role in parietal cell activation. Methods We used mass spectrometry (MS) to identify Rab27b in purified tubulovesicular membrane fractions and used immunoblot and immunofluorescence analyses to study its expression. Wild-type, constitutively active (Rab27bQ78L), and dominant negative (Rab27bN133I) forms of Rab27b were tagged with yellow fluorescent protein (YFP) and expressed in parietal cells using adenoviral constructs to study localization and function. Localization was visualized by fluorescence microscopy in resting and stimulated cells. Acid secretion in primary cell cultures was measured by aminopyrine accumulation. Results A tandem MS peptide mass fingerprint was matched to 7 peptides of Rab27b. Rab27b localized to tubulovesicle membranes, based on immunoblot and immunocytochemical analyses. Endogenous Rab27b, YFP/wild-type Rab27b, Rab27bQ78L, and Rab27bN133I all distributed throughout the cytoplasm of resting parietal cells. After stimulation, wild-type Rab27b and YFP-Rab27bQ78L translocated to the apical membrane, but YFPR-ab27bN133I did not. Expression of wild-type YFP-Rab27b or YFP-Rab27bQ78L did not affect acid secretion, whereas expression of Rab27bN133I almost completely inhibited acid secretion. Conclusions Rab27b is associated with tubulovesicle membranes in the parietal cell and Rab27b may play a role in stimulation-associated membrane recruitment and gastric acid secretion.
- Published
- 2011
448. Microsomal function in hepatitis B surface antigen healthy carriers: assessment of cytochrome P450 1A2 activity by the 14C-caffeine breath test.
- Author
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UCL - MD/MINT - Département de médecine interne, Horsmans, Yves, De Koninck, X, Geubel, André, Pauwels, Stanislas, UCL - MD/MINT - Département de médecine interne, Horsmans, Yves, De Koninck, X, Geubel, André, and Pauwels, Stanislas
- Abstract
The hepatitis B surface antigen (HBsAg) carrier state is associated with changes in hepatocellular function involving the cytochrome P450 (CYP) system. Among this system, CYP1A2 enzyme plays an important role in chemical carcinogenesis and in the metabolism of several drugs. We have thus investigated CYP1A2 function using two 14C-caffeine breath tests (3-methyl-14C; C3BT and 7-methyl-14C caffeine; C7BT) in 12 HBsAg healthy carriers and 8 healthy volunteers matched for 14C-aminopyrine breath test values. HBsAg carriers exhibited lower C3- and C7BT values than normal controls. This difference, however, did not reach statistical significance except for C7BT values normalised for aminopyrine breath test values. Our data thus do not support the association between viral presence and CYP1A2 dysfunction.
- Published
- 1995
449. Reliability of aminopyrine breath test using a single breath collection.
- Author
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UCL - MD/MINT - Département de médecine interne, Horsmans, Yves, Geubel, André, Pauwels, Stanislas, UCL - MD/MINT - Département de médecine interne, Horsmans, Yves, Geubel, André, and Pauwels, Stanislas
- Published
- 1995
450. [Activity of the xenobiotic metabolism system under the effect of chemical pollution of the atmosphere and water]
- Author
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L Kh, Mukhambetova, A A, Nasonova, and S I, Dolinskaia
- Subjects
Male ,Air Pollutants ,Aniline Compounds ,Hydroxylation ,Methylation ,Rats ,Xenobiotics ,Kinetics ,Cytochromes b5 ,Cytochrome P-450 Enzyme System ,Microsomes, Liver ,Animals ,Glucuronosyltransferase ,Aminopyrine ,Water Pollutants, Chemical - Abstract
Functional state of the system involved in biotransformation of xenobiotics in animal liver tissue was studied under conditions of combined chemical contamination of atmospheric air and water simulating the typical real loading. The model loading studied caused in some cases an induction of the microsomal monooxygenases without activation of UDP-glucuronosyl transferase, but simultaneously with accumulation of malonic dialdehyde; this suggests that metabolic alterations observed may be involved in development of pathology.
- Published
- 1993
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