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J R Powell

Publications and source records attributed to J R Powell.

At least 145 records · Page 8Linked to original sources
PubMed1984

Histamine H2-antagonist drug interactions in perspective: mechanistic concepts and clinical implications.

Histamine H2-antagonists have the ability to produce fundamental changes in the absorption and disposition of other drugs. However, there are similarities and differences between the H2-antagonists in this respect, depending on the process involved. By increasing the intragastric pH any H2-antagonist has the potential of altering the absorption of weak acids or weak bases. However, since the rise in intragastric pH is not immediate, as with antacids, this type of interaction might be avoided for concomitantly administered, rapidly absorbed drugs. Whereas cimetidine inhibits hepatic mixed-function oxidase drug metabolism, ranitidine does not have this characteristic. Clinical studies have found that cimetidine produces a 20 to 60 percent decrease in the clearance of 23 drugs (such as warfarin, theophylline, quinidine, phenytoin, imipramine, propranolol, nifedipine). Marketed and investigational H2-antagonist drugs differ in their ability to inhibit drug metabolism due to the combined characteristics of cytochrome P-450 binding affinity and therapeutic dosage. Cimetidine also inhibits the renal-tubular secretion of other weak bases (such as procainamide). Management suggestions are presented to help clinicans predict and avoid failure in drug therapy as a result of these drug interactions.

Absorption↗
PubMed1984

Genetic heterogeneity among Caribbean populations of Aedes aegypti.

Using starch gel electrophoresis, we have analyzed genetic variation at 11 loci in 18 Caribbean collections of Aedes aegypti. Our results show that, while there is some relationship between geographic proximity and genetic distance, the overall picture among islands is one of gene frequency patchiness , with some collections clearly not conforming to any geographic pattern. We attribute this to the combined effects of high rates of gene flow among islands and with the mainland American continent, and the activities of various vector control agencies in the region.

Aedes↗
PubMed1984

Inhibition of theophylline clearance by cimetidine but not ranitidine.

This study was designed to compare the effects of equivalent therapeutic doses of two H2 antagonists, cimetidine and ranitidine, on theophylline pharmacokinetics and to determine whether the previously described cimetidine-theophylline interaction is dose dependent. Twelve healthy adult men were given a 6-mg/kg intravenous aminophylline dose on four occasions. Subjects were randomly assigned four treatments: no treatment (control); cimetidine, 1,200 mg/day; cimetidine, 2,400 mg/day; and ranitidine, 300 mg/day. Cimetidine, 1,200 mg/day, significantly decreased theophylline clearance by 36% (range, 22% to 49%) and increased the mean elimination half-life from 5.7 hours (control) to 9.2 hours. A significant difference was not found between the two cimetidine dosages, indicating dose independence of the interaction over the dosage range studied. Ranitidine did not significantly alter theophylline pharmacokinetics. Theophylline plasma protein binding was not affected by any treatment. The relative effects of cimetidine and ranitidine on the elimination of cytochrome P-450 metabolized drugs such as theophylline indicate a useful property of ranitidine as compared with cimetidine.

Adult↗
PubMed1983

Complex formation of human Val354-plasminogen with streptokinase.

A controlled digestion of native human plasminogen (Glu1-plasminogen) from either carbohydrate variant 1 or 2 with pancreatic elastase yields, among others, an activatable fragment, designated Val354-plasminogen (Pgc). This species represents the smallest human plasminogen fragment (ca., 50,000 Mw) known to bind to Sepharose-lysine. Pgc forms a tight equimolar complex with streptokinase, as determined by sucrose density ultracentrifugation, whether formed from Val354-plasminogen or Val354-plasmin. The Val354-plasmin-streptokinase complex readily activates ovine plasminogen, which is normally insensitive to streptokinase, and this complex is essentially inactive toward casein, similar to the equimolar complexes formed with Lys77-plasmin and the elastase fragment, Val442-plasmin.

Animals↗
PubMed1983

Amino acid sequence analysis of the asparagine-288 region of the carbohydrate variants of human plasminogen.

The amino acid sequences of the two major carbohydrate variants in the region of Asn288 have been determined. A peptide isolated from plasminogen variant 1, which contains a complex-type Asn288-linked oligosaccharide, was found to possess the amino acid sequence-Ser280-Ala-Gln-Thr-Pro-His-Thr-His-Asn(CHO)-Arg-Thr290-Pro-Glu-, in agreement with the previously published sequence [Sottrup-Jensen, L., Claeys, H., Zajdel, M., Petersen, T. E., & Magnusson, S. (1978) in Progress in Chemical Fibrinolysis and Thrombolysis (Davidson, J. F., Rowan, R. M., Samama, M. M., & Desnoyers, P. C., Eds.) Vol. 3, pp 191-209, Raven Press, New York]. A similar peptide isolated from plasminogen variant 2 did not contain oligosaccharide but possessed an amino acid sequence identical with the corresponding variant 1 peptide. Thus, the basis for the lack of the complex-type oligosaccharide in human plasminogen variant 2 does not reside in substitution of essential amino acid residues in the region of the Asn288-linked glycosylation site.

Amino Acid Sequence↗
PubMed1983

Factors affecting the termination of cardiovascular actions of 10,10-difluoro,13-dehydroprostacyclin.

Experiments were conducted to determine why 10,10-difluoro,13-dehydroprostacyclin (DF2-PGI2) has a long vascular relaxant activity in vitro but like PGI2 has a short duration of effect in vivo. DF2-PGI2 produced depressor responses in anesthetized dogs which were not affected by nephrectomy suggesting that the kidney was not responsible for the termination of action. DF2-PGI2 given intravenously or into the ascending aorta produced depressor responses of a similar magnitude but injection of the same doses into the hepatic portal circulation resulted in a large attenuation of responses. The data suggest hepatic, but not pulmonary, metabolism of DF2-PGI2. Injection or infusion of PGI2 and DF2-PGI2 into the hindlimb circulation caused vasodilatation of a similar duration suggesting diffusion from tissue sites as another mechanism of termination of action.

Acetylcholine↗
PubMed1983

Interspecific cytoplasmic gene flow in the absence of nuclear gene flow: evidence from Drosophila.

mtDNA polymorphism has been studied by restriction endonuclease site variation in Drosophila pseudoobscura and its sibling species D. persimilis. Eight enzymes have been used to study 54 isofemale strains from areas where the two species are sympatric and D. pseudoobscura is allopatric. Where sympatric, 75-80% of the strains have mitochondrial genomes found in both species. Where allopatric, D. pseudoobscura has diverged to the point where none of the strains have mtDNA in common with D. persimilis. The most likely explanation for this observation is that where sympatric the two species hybridize frequently enough to keep their mtDNA from diverging. However, hybridization has not prevented their nuclear genomes from diverging, perhaps due to selection against nuclear gene introgression contrasted with little or no selection against mtDNA introgression. These observations suggest that nuclear and cytoplasmic genomes have different evolutionary dynamics.

Animals↗
PubMed1983

Population genetics of Drosophila amylase. IV. Selection in laboratory populations maintained on different carbohydrates.

Two polymorphic systems impinging on alpha-amylase in Drosophila pseudoobscura have been studied in laboratory populations maintained on medium in which the only carbohydrate source was starch (the substrate of amylase) and replicas maintained on medium in which the only carbohydrate source was maltose (the product of amylase). The two polymorphic systems were alleles at the structural gene (Amy) coding for the enzyme (allozymes) and variation in the tissue-specific expression along the adult midgut controlled by several genes. In the seven populations on maltose medium little consistent change was noted in either system. In the seven populations on starch medium, both polymorphisms exhibited selective changes. A midgut pattern of very limited expression of amylase rose in frequency in all starch populations, as did the frequency of the "fast" (1.00) Amy allele. The overall specific amylase activity did not differ between starch-adapted and maltose-adapted flies.--The results, along with previous studies, indicate that when a gene-enzyme system is specifically stressed in laboratory populations, allozymes often exhibit selective differences. Such results make the selectionist hypothesis at least tenable. Furthermore, the fact that both types of polymorphisms responded to selection indicates the role of structural gene vs. gene regulation changes in adaptive evolution is not an either/or question but one of relative roles and interactions.

Alleles↗
PubMed1983

The pharmacokinetic basis for H2-antagonist drug interactions: concepts and implications.

In 1978, less than two years after its release, published reports indicated that cimetidine caused an increased prothrombin time in patients receiving warfarin. It has since been established that cimetidine inhibits the hepatic metabolism of at least 15 other drugs. The time course for the interaction is rapid with the onset and termination detectable within the first day of starting or stopping cimetidine. In vitro and clinical data indicate that the interaction is dependent upon the cimetidine dose or plasma concentration, but its limits are not well defined. Cimetidine inhibits the metabolism of drugs that are primarily eliminated by the hepatic mixed-function oxidase, microsomal enzymes. The degree to which cimetidine decreases drug clearance is dependent upon the fraction of drug eliminated by the inhibited metabolic routes, the route of administration for high hepatic extraction drugs, and the patient's characteristics. Cimetidine decreases the clearance of various drugs from 20-60%. The interpatient variability in the effects of cimetidine for any given drug can be considerable. Since cimetidine and ranitidine have been reported to decrease indocyanine green clearance, it has been assumed that H2-antagonists decrease functional hepatic blood flow. However, there is direct and indirect evidence indicating there is not a significant effect on liver blood flow. At similar therapeutic doses, ranitidine does not decrease the clearance of theophylline, phenytoin, diazepam, propranolol, ethanol, antipyrine, and aminopyrine. Ranitidine does not alter the prothrombin time in subjects receiving warfarin. Differences between cimetidine and ranitidine on drug metabolism appear to exist both because the cytochrome P-450 binding affinity for ranitidine is about 10 times lower than cimetidine and because the daily ranitidine dose is 1/4 that of cimetidine. The imidazole ring and lipophilicity of cimetidine are characteristics that favor inhibition of drug metabolism. Since both cimetidine and ranitidine change the gastric pH and fluid volume, there is the potential for altering drug absorption. Drug distribution does not appear to be influenced by either agent. Although neither cimetidine nor ranitidine significantly alters the glomerular filtration rate, their influence on renal drug elimination is not well characterized. The numerous case reports of therapeutic failure primarily from drug toxicity are basically due to cimetidine inhibition of metabolism. This cimetidine effect (and lack of ranitidine effect) may help explain differences in the adverse effect profiles between cimetidine and ranitidine and may be important for a number of uninvestigated drugs.

Absorption↗
PubMed1982

Intrauterine pressure changes during dysmenorrhea therapy.

The treatment of primary spasmodic dysmenorrhea with prostaglandin synthetase/receptor site inhibitors such as mefenamic acid (Ponstel) is becoming accepted. Recent improvements in intrauterine pressure recording have made the acquisition of reliable, physiologic data possible. These data have been used to provide objective evaluation of the effectiveness of drug therapy as part of a larger subjective investigation. Analysis of these data shows that mefenamic aid causes rapid, dramatic reductions in parameters of uterine pressure and work. Complete loss of uterine contractile activity was found in 46.2% of patients. Subjective relief was obtained in all patients receiving mefenamic acid in this sample.

Cyclooxygenase Inhibitors↗