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Biomedical subjects

R Vargas

Publications and source records attributed to R Vargas.

At least 109 records · Page 6Linked to original sources
PubMed1987

Role of misoprostol in reducing aspirin-induced gastrointestinal blood loss in arthritic patients.

Nonsteroidal anti-inflammatory drugs are used to control pain and inflammation in arthritic disorders. When used at recommended anti-inflammatory dose levels, however, they often produce injury to the gastric and duodenal mucosa and concomitant blood loss. A double-blind, parallel, placebo-controlled study was conducted to assess the effectiveness of misoprostol, a synthetic analogue of prostaglandin E1, in preventing gastrointestinal blood loss induced by acetylsalicylic acid in patients with degenerative joint disease. Forty-five arthritic patients (22 women and 23 men) were admitted to the study. All patients had received treatment with 3,900 mg of acetylsalicylic acid per day in four divided doses for at least two weeks and continued to receive that regimen for the duration of the study. Red blood cells were tagged with chromium-51, and fecal blood loss was determined from Days 4 to 7. Patients with a mean blood loss of at least 1.5 ml per day were randomly allocated to receive either placebo or 200 micrograms of misoprostol four times daily for seven days. Fecal blood loss was measured daily, and the results were compared with baseline determinations. Of 41 patients who completed the study, 19 were treated with misoprostol. Of these, 11 patients (57.9 percent) had at least a 50 percent reduction in blood loss. Of 22 patients receiving placebo, only one had a 50 percent reduction in blood loss (p = 0.003; Fisher's exact test). Mean blood loss in patients using misoprostol was reduced from 3.65 +/- 2.51 to 1.57 +/- 0.86 ml per day, whereas among those taking placebo, mean blood loss did not significantly change (2.98 +/- 1.24 to 2.79 +/- 1.63 ml per day). The difference in blood loss between the misoprostol and placebo groups was significant (p = 0.0023; Wilcoxon test). In those patients who completed the study, no significant changes were detected on laboratory tests. In conclusion, misoprostol effectively reduced fecal blood loss in arthritic patients treated with acetylsalicylic acid.

Alprostadil↗
PubMed1987

Enteric coating of fenoprofen calcium reduces gastrointestinal microbleeding.

The effects of plain and enteric-coated fenoprofen calcium (Nalfon, Dista, Indianapolis, Ind.) on gastrointestinal microbleeding were studied in 32 normal male volunteers in a randomized, open-label, parallel trial at two inpatient research facilities. A 1-week placebo (baseline) period preceded 2 weeks of fenoprofen therapy (enteric coated or plain, 600 mg q.i.d.). Fecal blood loss was measured by 51Cr-tagged erythrocyte assay and averaged over days 4 to 7 (baseline) and 11 to 14 and 18 to 21 (active therapy). At one center gastrointestinal irritation was evaluated endoscopically before and after active therapy. Endoscopy showed both formulations to cause mucosal damage not evident by subject-reported symptoms. Four of the 16 subjects developed asymptomatic duodenal ulcers. Mean daily fecal blood loss was significantly lower (P = 0.03) with enteric-coated (mean +/- SD, 1.104 +/- 0.961 ml/day) than with plain fenoprofen calcium (mean +/- SD, 1.686 +/- 0.858 ml/day), suggesting that tolerance of fenoprofen can be improved with administration in an enteric-coated form.

Adult↗
PubMed1987

The effect of various dose regimens of famotidine on basal nocturnal and meal-stimulated gastric secretion.

The antisecretory profile of the H2-receptor antagonist famotidine was studied with various oral doses and regimens in 10 healthy volunteers with high basal acid output (greater than or equal to 5 mEq/hr). Doses included 10, 20, and 40 mg at 9 PM and 9 AM and also 40 mg at 9 PM only. In the 22 hours after the PM doses, overnight (midnight to 7 AM) basal acid secretion was evaluated. Daytime meal-stimulated secretion was assessed at 7 AM, 12 noon, and 5 PM. Doses of 10, 20, and 40 mg inhibited fasting nocturnal basal secretion by 69%, 86%, and 83% to 94%, respectively (P less than 0.01). Meal-stimulated secretion at 7 AM (10 hours after administration) was inhibited by 28% and 39% (P less than 0.01) by only the 40 mg doses. The response to the 12 noon meal was inhibited by the 9 AM doses of 10, 20, and 40 mg by 45%, 75%, and 85%, respectively (P less than 0.01). The effect of a 40 mg dose given at 9 PM only had dissipated by breakfast (7 AM). The response to the 5 PM meal was suppressed by the 20 and 40 mg doses given at 9 AM by 22% and 35%, respectively (P less than 0.05). Suppression was present in only eight of the subjects after the 20 mg dose but in all 10 after the 40 mg dose. The effect on basal gastric aspirate pH values paralleled those seen on acid output. An association was found between mean plasma concentrations of famotidine and mean inhibition of meal-stimulated acid secretion. However, individual values may not be predictive.

Adult↗
PubMed1987

The vasodilatation induced by hydroperoxy metabolites of arachidonic acid in the rat mesenteric and pulmonary circulation.

The effects of 15-hydroperoxy metabolites of arachidonic acid on vascular tone were evaluated in the perfused mesenteric preparation, the isolated perfused lung and segments of pulmonary arteries of the rat. In the mesenteric preparation, precontracted with phenylephrine, both 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE, ED50 1.6 nmol) and 8,15-dihydroperoxy-5,9,11,13-eicosatetraenoic acid (8,15-diHPETE, ED50 0.3 nmol) induced dose-dependent vasodilatation, whereas 5,15-diHPETE (0.2-100 nmol) had no effect. Prostacyclin (ED50 0.01 nmol) was, however, more potent than the hydroperoxides. In the rat isolated lung, precontracted with the stable thromboxane agonist U-46619, dose-dependent decrease in the perfusion pressure occurred with 15-HPETE(ED50 40 nmol), 5,15-diHPETE (ED50 30 nmol) and 8, 15-diHPETE (ED50 7 nmol) while 13-hydroperoxide of linoleic acid had no effect. Prostacyclin was 10 times more potent than 8, 15-diHPETE. The vasodilator effects were not affected by indomethacin. In both endothelium intact and denuded rat pulmonary arteries the hydroperoxides 15-HPETE, 8,15-diHPETE, and 5,15-diPETE induced dose-dependent relaxation. The hydroperoxide, 8,15-diHPETE was at least 3 times more potent than 15-HPETE or 5,15--diHPETE. The hydroperoxides had no effect on the basal tone of vessel segments and the relaxation induced by 15-HPETE was not attenuated by methylene blue (5 microM). These data indicate that 8,15-diHPETE may be a significant endothelium-independent vasodilator product of arachidonate lipoxygenation.

Animals↗
PubMed1987

Relaxing effects of 15-lipoxygenase products of arachidonic acid on rat aorta.

In the presence of indomethacin, arachidonic acid relaxes precontracted rings of rat aorta only when the endothelium is intact. Arachidonate-induced, endothelium-dependent relaxation is potentiated by superoxide dismutase. In contrast, linoleic acid (LA) contracts endothelium-intact and -denuded rings. Arachidonate is metabolized in endothelial cells by both cyclo-oxygenase and 15-lipoxygenase. Therefore, we determined the vasodilatory effect of 15-lipoxygenase products. The products generated by soybean lipoxygenase (SLO) from arachidonate in the bioassay bath relax precontracted, de-endothelialized ring segments of rat aorta. This relaxation is potentiated by superoxide dismutase and is more prominent when high concentrations of SLO are used. The main metabolites recovered from the bioassay bath were 5,15-dihydroperoxyeicosatetraenoic acid and 8,15-dihydroperoxyeicosatetraenoic acid. At lower concentrations of SLO the degree of relaxation is less and the major product is 15-hydroperoxyeicosatetraenoic acid. LA is metabolized by SLO to 13-hydroperoxyoctadecadienoic acid. The relaxation induced by the incubation of LA with SLO in endothelium-denuded rings is less than that obtained with arachidonic acid. In endothelium-denuded rings that were precontracted with phenylephrine authentic 15-hydroperoxyeicosatetraenoic acid did not induce clear effect (at 40 microM 15-hydroperoxide caused relaxation, whereas at 15 microM induced small contraction) and 13-hydroperoxyoctadecadienoic acid of LA induced contraction. Neither 5,15-dihydroperoxyeicosatetraenoic acid nor 8,15-dihydroperoxyoctadecadienoic acid (1-15 microM) induced a well defined relaxation. This study indicates that arachidonic acid is metabolized by SLO to a vasodilatory compound(s) that is possibly derived from 15-hydroperoxyeicosatetraenoic acid.

Animals↗
PubMed1986

Comparison of effects of oral and intravenous famotidine on inhibition of nocturnal gastric acid secretion.

In this double-blind, placebo-controlled, four-way crossover, randomized study, eight high-secretor (more than 5 meq per hour) volunteers received 20 mg of famotidine by mouth, 10 mg intravenously, and 20 mg intravenously at 9 P.M. Volume, acid content, and pH of continuous gastric aspirates were measured hourly from one to at least 12 hours after treatment. Plasma concentrations of famotidine were determined at specified intervals. All famotidine doses produced marked suppression of gastric secretion. The mean total output was 1,196.3, 526.8, 414.9, and 518.0 ml for placebo, the 10-mg intravenous famotidine dose, the 20-mg intravenous dose, and the 20-mg oral dose, respectively. The latter three values were significantly different from that of placebo at p less than 0.01. The mean total acid output was 105.3, 8.3, 2.3, and 6.2 meq, respectively, and the acid output for all three doses was significantly different from that of placebo at p less than 0.01. The onset of antisecretory effect was noted as early as one hour after dosing. The mean gastric aspirate pH values were 1.7, 5.5, 6.2, and 4.4 during the second hour after placebo, the 10-mg intravenous dose, the 20-mg intravenous dose, and the 20-mg oral dose, respectively, with the treatment pH values significantly different from the placebo pH value at p less than 0.01. Higher mean pH values were reached at seven, eight, and nine hours after the 20-mg intravenous dose than after the 10-mg intravenous dose (p less than 0.05). By the 12th hour after administration of the 10-mg intravenous dose, pH values had returned to baseline in all but one subject. After the 20-mg intravenous dose, a similar loss of effect occurred in one subject at 12 hours and in all subjects by 15 hours. Plasma concentrations of famotidine greater than 50 ng/ml were associated with an acid output inhibition of more than 80 percent, whereas high (more than 90 percent) as well as low (less than 50 percent) inhibition was observed at famotidine concentrations below 50 ng/ml.

Administration, Oral↗
PubMed1986

Ajoene, the antiplatelet principle of garlic, synergistically potentiates the antiaggregatory action of prostacyclin, forskolin, indomethacin and dypiridamole on human platelets.

Ajoene, the major antiplatelet compound derived from garlic, synergistically potentiates the antiaggregatory action of prostacyclin, forskolin, indomethacin and dypiridamole. For collagen-induced platelet aggregation in human PRP, the ID50 for ajoene is 95 +/- 5 microM. However, in the presence of the antiaggregatory drugs mentioned above, the ID50 for ajoene decreases more than what would be predicted on the basis of simple additive effects. Similarly, the ID50 for prostacyclin decreases from 1 nM to 0.15 nM in the presence of 80 microM ajoene. Isobolic curves for the various combinations of ajoene with prostacyclin or indomethacin exhibit departure from linearity, as predicted for a potentiated synergism between ajoene and these drugs. Dypiridamole, which in PRP has very little effect on the dose-response curve for ajoene, when assayed in whole blood decreases the ID50 for ajoene by a factor of four. These results demonstrate that the antithrombotic potential of ajoene is substantially increased in the presence of physiologically and pharmacologically active antiplatelet agents.

Blood Platelets↗
PubMed1986

Stagewise decline in the activity of brain protein synthesis factors and relationship between this decline and longevity in two rodent species.

The activities of brain initiation factor 2 and brain elongation factor 1, which function as rate-limiting in total protein synthesis, and estimations of brain weight were followed during postnatal life in the rat and the mouse. Both activities decreased in parallel while cumulative brain weight increased. Three exponential components were required for the mathematical expression of each of the three processes in semilogarithmic plots against time. The acceleration curves for the activities and tissue weight demonstrated a mirror image symmetry. Within the general pattern of diminution with age, the negative acceleration of the activities and the positive acceleration of the brain weight displayed repeated bursts. The activities of both factors could also be arranged into several regression lines in log/log plots against time. Significantly, in these plots, the regression line calculated for the whole set of data for each factor activity showed that the value of the ratio of the slopes (mouse to rat) was inversely related to the square root of the ratio of species longevity and was in agreement with the power law relating life spans of cells to species longevity (Röhme, Proc. Natl. Acad. Sci. U.S.A., 78 (1981) 5009).

Animals↗
PubMed1984

Heterogeneity of protein-synthesis initiation factors in developing and aging rat brain.

Protein synthesis initiation factors from rat brain were assayed in vitro through the formation of the initiator Met-tRNA X initiation factor 2 X GTP ternary complex. The initiation factor showed different intrinsic activity with increase in age. This difference was elicited by additions of high-salt ribosomal-wash protein to incubation mixtures that were already saturated with protein preparations from brains of older animals. This qualitative difference was further documented by examining the sensitivity of the activities of the initiation factor to spermidine and to temperature. The sensitivity to these effectors varied with age. By fitting an exponential decay model to data from the temperature experiments, it was possible to demonstrate that the preparations of the initiation factor from older brains behaved as a multicomponent system. The brain preparations from older animals contained at least two subpopulations of initiation factor. The fractions of these two gross subclasses varied, inversely one to the other, with age.

Aging↗
PubMed1983

Age-dependent decrease in the activity of protein-synthesis initiation factors in rat brain.

The age-dependent reduction of brain protein synthesis was examined at the initiation step of translation in the rat. Activity of brain initiation factor 2, as well as that of other eukaryotic initiation factors that contribute to the binding of initiator aminoacyl-tRNA to ribosomes, was found to decrease with age and to decline parallel to the decrease in total protein synthesis and brain elongation factor 1 activity. Change in the activity of initiation factors was demonstrated by the results of two different assays which compared favorably with each other. Decreased activity of preparations of initiation factors derived from older animals was observed in: (1) saturating conditions; (2) mixtures of preparations from different ages; and (3) both major cell fractions, i.e. cell sap and microsomes.

Age Factors↗