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Biomedical subjects

R Vargas

Publications and source records attributed to R Vargas.

At least 91 records · Page 5Linked to original sources
PubMed1990

Pharmacokinetics, pharmacodynamics, and minimum effective clinical dose of intravenous nicardipine.

Nicardipine hydrochloride was administered intravenously to two groups of hypertensive patients: one group of 37 patients with mild to moderate hypertension and one group of 20 patients with severe hypertension. In the first group, doses of 0.5, 1, 2, and 4 mg/hr, as well as placebo, were infused for 48 hours in a double-blind fashion. Blood pressure and heart rate were monitored for this period and for the 24 hours after the infusion was discontinued. Significant decrements in blood pressure were noted with all doses; 4 mg/hr produced lowering that was greater than all other doses; 1 and 2 mg/hr produced lowering that was greater than 0.5 mg/hr but that were not different from each other. Excellent correlation of blood pressure reduction and plasma level was observed and linear kinetics existed. In the severe hypertensive patients, 1, 2, 4, 5, and 8 mg/hr were infused to established minimal and ineffective doses. One milligram per hour was an ineffective dose; 4, 5, and 8 mg/hr all produced significant reductions over the course of the study that were undistinguishable from each other. Two milligrams per hour produced modest reductions in blood pressure. Blood pressure reduction also correlated with plasma levels in the severe hypertensive group.

Analysis of Variance↗
PubMed1990

Attenuation of vascular relaxation and cyclic GMP responses by cyclosporin A.

The effect of Cyclosporin A (CsA) on vascular vasomotor responses was determined in two isolated tissue preparations. The first preparation was the rat mesenteric vascular bed which was constricted by phenylephrine (EC80) and perfused with CsA (8.32 x 10(-8) to 8.32 x 10(-6) M). Vasodilation responses to acetylcholine, bradykinin and the calcium ionophore, A23187, were impaired, as was the response to sodium nitroprusside at high CsA concentrations. Indomethacin had no effect suggesting that the CsA effect is unrelated to the synthesis of cyclooxygenase products. In the second preparation, thoracic aortic rings from rats treated with CsA (5-10 and 20-50 mg/kg/daily for 3 and 1 weeks, respectively) were used. Aorta rings precontracted by phenylephrine (EC80) also showed impaired responses to both endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilators. Furthermore, a marked decrease of the guanosine 3',5'-cyclic monophosphate (cGMP) content in aortic preparations was found to accompany the in vivo effect of CsA on relaxation. In addition, exposure of aortic rings to CsA (8.32 x 10(-8) to 8.32 x 10(-6) M) in vitro, also inhibited markedly the cGMP response induced by acetylcholine or sodium nitroprusside. This effect of CsA was not modified by isobutyl methylxanthine, a phosphodiesterase inhibitor. We conclude that CsA acts directly on the vascular smooth muscle; and speculate that CsA may compromise the response to vasodilators by inhibiting cGMP formation.

Acetylcholine↗
PubMed1990

[Histocompatibility antigens and acute vascular purpura].

INTRODUCTION: Some kidney diseases are associated to HLA antigens. Nyulassy found an increase in HLA-B35 in patients with Henoch-Schönlein's purpura suffering nephritis (HSP-N). Our study searched for associations of HLA antigens and anaphylactoid purpura nephritis in Mexican mestizo patients. MATERIAL AND METHODS: HLA-A,B, and C antigens were detected by two-step microcytotoxicity in 22 patients with HSP-N and compared to those of 665 healthy subjects of the same ethnic background. RESULTS: A significant association was found between HSP-N and HLA-Aw19 single (pc less than 0.05) or in haplotype form (Aw19-B35) (pc less than 0.005). HLA B35 alone was associated to HSP-N but only at non corrected level (pc less than 0.05). DISCUSSION: The significant association between HLA-Aw19 and Aw19-B35 and HSP-N may indicate a risk factor in Mexican mestizo patients to develop this case.

Adolescent↗
PubMed1990

[Intrahepatic cholestasis in pregnancy and perinatal risk].

The main purpose of this study was to analyze the accuracy of severity criteria applied in cholestatic jaundice in pregnancy related to health problems in the newborn. The sample, 209 cases, is formed by the total of hospital patients discharges from the Pathologic Pregnancy Unit. Severe cholestatic jaundice (59.3% of cases) presented early itching and impeding premature delivery as the most frequent severity criteria. We found that the greater number of severity criteria, the worse prognosis for the newborn, as shown by birth weight under 2,500 g and Apgar at the minute of 7 or less. Both differences were statistically significant (p = 0.0001; p = 0.0348). No maternal or perinatal deaths were found. Our conclusions are: 1. Severity criteria used in cholestatic jaundice of pregnancy are valied and 2. Clinical management of cases is appropriate, since the major risk reported (perinatal mortality) was absent and maternal and perinatal morbidity were less than those reported in previous studies.

Birth Weight↗
PubMed1990

Mechanism of cyclosporin potentiation of vasoconstriction of the isolated rat mesenteric arterial bed: role of extracellular calcium.

Hypertension is a serious side-effect of the clinical use of Cyclosporin A (CsA). One notion is that alterations of vascular reactivity contribute to this hypertension. In this study we used the isolated rat mesenteric vascular bed to test the specific hypothesis that CsA modifies vascular calcium regulation to potentiate vascular contractility. Mesenteric vessels from CsA-treated rats (10 mg/kg/day i.m. for 7 days) exhibited significantly greater vasoconstrictor responses to exogenous norepinephrine (NE) and potassium-induced depolarization than those of vehicle-treated animals. Similarly, in vitro CsA (8.3 X 10(-8) to 8.3 X 10(-6) M) augmented in a concentration-dependent manner both the sensitivity and the maximum response to NE and potassium. This effect of CsA on vasoconstriction was critically dependent on the presence of external calcium [( Ca++]o). The degree of vasoconstriction potentiation correlated significantly with the [Ca++]o which was used during exposure of the mesenteric bed to CsA. Reapplication of external calcium in the presence of CsA to "calcium-depleted" preparations increased significantly the amplitude of subsequent NE responses in a calcium-free medium. Thus, CsA-potentiated NE responses, once established, were not reversed by removing external calcium; however, attenuation occurred with the intracellular calcium antagonist dantrolene. Verapamil and nifedipine blocked potassium-elicited responses, but failed to prevent the CsA effect on NE-induced vasoconstriction. We conclude that CsA potentiation of vasoconstriction depends on extracellular calcium, and results from an enhanced transmembrane calcium transport. We speculate that CsA also increases the filling of intracellular stores of releasable calcium. These effects lead to greater calcium influx and greater intracellular calcium release upon stimulation.

Animals↗
PubMed1989

Production of hapten-specific T cell hybridomas and their use to study the effect of ultraviolet B irradiation on the development of contact hypersensitivity.

We produced a series of T cell hybridomas that produce IL-2 when cultured with syngeneic APC coupled to FITC or TNP. These hybridomas are hapten specific and Ia restricted. The hybridomas were used to detect hapten-bearing APC in draining lymph nodes of mice sensitized with trinitrochlorobenzene or FITC in vivo. Hapten-bearing APC capable of stimulating the hybridomas were detectable in draining lymph nodes of hapten-painted mice within 3 h after sensitization. The ability of lymph node APC to stimulate the hybridomas peaked at 24 h and declined by 48 h. The dendritic cell subpopulation was the subpopulation of cells that were found in the regional lymph nodes of hapten-painted animals that were capable of stimulating the hybridomas to produce IL-2. Prior treatment of the skin with low dose UVB irradiation before epicutaneous application of contact sensitizers significantly reduced the capacity of hapten-bearing APC to stimulate the hybridomas. This observation was corroborated by results obtained from flow microfluorometry analysis of lymph node cells from FITC-sensitized mice. Lymph node dendritic cells obtained from FITC-painted mice contain a brightly staining group of cells by flow microfluorometry analysis. Lymph node dendritic cells from FITC-painted, UVB-irradiated mice did not contain this brightly staining population. These results indicate that low dose, local UVB irradiation may affect APC migration and/or function. We believe that these hybridomas will prove to be useful tools in the study of the development and regulation of contact hypersensitivity.

Animals↗
PubMed1989

Monoexponential analysis of plasma disappearance of 99mTc-DTPA and 131I-iodohippurate: a reliable method for measuring changes of renal function.

Glomerular filtration rate and effective renal plasma flow were measured in 170 subjects using monoexponential analysis of plasma disappearance curves for 99mTc-DTPA and 131I-iodohippurate after single injection. In the current study population, glomerular filtration rate and effective renal plasma flow decreased with increasing age, were less in females than in males, and were less in hypertensives than in normotensives. Differences in glomerular filtration rate according to age and sex in the current study were similar to those reported using traditional creatinine clearance methodology. Monoexponential treatment of plasma isotope disappearance gave reproducible values for both glomerular filtration rate and effective renal plasma flow when measured either during the day or on a daily basis. Intraindividual coefficient of variation was less than 10% for both 99mTc-DTPA and 131I-iodohippurate clearances derived from monoexponential analysis. These results demonstrate that monoexponential analysis of plasma disappearance curves for 99mTc-DTPA and 131I-iodohippurate after a single injection is a useful method for evaluating changes in renal hemodynamics either during chronic drug therapy or acutely after single dose administration.

Adult↗
PubMed1989

Inhibition of myointimal proliferation of the rat carotid artery by the peptides, angiopeptin and BIM 23034.

Proliferation of vascular smooth muscle is an early and major event in the formation of an atherosclerotic lesion. Here we report for the first time the inhibitory effects on myointimal proliferation of the rat carotid artery by a synthetic peptide, angiopeptin, and its closely related congener, BIM 23034. Proliferation was initiated in the carotid artery of anesthetized rats by air-drying of the endothelium. After 15 days the rats were killed and the carotid artery was pressure-fixed and subjected to morphologic analysis for evaluation of the degree of myointimal thickening. Five synthetic somatostatin-like peptides were tested by pretreating rats (20 and 50 micrograms/kg/rat s.c. daily) for 2 days prior to and for 5 days after the endothelial injury. Angiopeptin and the closely related octapeptide (BIM 23034) significantly inhibited myointimal thickening. Angiopeptin was also effective when the pretreatment period was reduced from 2 days to 30 min. The inhibitory effect of angiopeptin was further confirmed in an additional experiment involving [3H]thymidine incorporation. In this experiment angiopeptin (100 micrograms/kg/day s.c.) was also administered for 2 days prior to and five days following the endothelial injury and it significantly inhibited thymidine uptake. All the peptides tested inhibit the release of growth hormone. However, only angiopeptin and BIM 23034 inhibited myointimal proliferation. Thus the effect of angiopeptin and its congener is unlikely to be mediated through growth hormone. Since angiopeptin inhibits myointimal proliferation it may have clinical utility in preventing restenosis following angioplasty and coronary artery by-pass procedures.

Animals↗
PubMed1989

Role of the endothelium and arginine peptides on the vaso-motor response of porcine internal mammary artery.

The long-term patency of the internal mammary artery (IMA) graft is of considerable interest owing to its extensive use in myocardial revascularization. The aim of the present study was to elucidate the role of endothelium in modulating the responses of the porcine IMA to several vasoactive drugs. Isolated ring segments of porcine IMA contracted in a reproducible and dose dependent manner to phenylephrine, potassium chloride and the thromboxane mimic U46619, but the responses to serotonin, histamine and ATP were significantly less prominent. Both acetylcholine and bradykinin elicited endothelium-dependent relaxation which was not inhibited by indomethacin, but by methylene blue, an inhibitor of soluble guanylate cyclase. These two endothelium-dependent drugs and two endothelium-independent relaxing drugs, nitroprusside and nitroglycerin relaxed the IMA in a dose dependent manner which was associated with an elevation of cyclic GMP. The endothelium dependent vasodilator peptides such as bradykinin contain L-arginine in their sequence. Benzoyl derivatives of L-arginine but not L-arginine relaxed the IMA in a dose dependent manner. These data confirm and extend exploratory studies performed with a simpler vascular model which indicate that the precursor of endothelium derived relaxing factor (EDRF) is an arginine moiety.

Animals↗
PubMed1989

The effects of enoximone on renal function in patients with congestive heart failure.

Enoximone is an investigational cardiotonic agent with positive inotropic and vasodilatory properties. In this protocol the effects of enoximone on parameters of renal function in patients (n = 14) with New York Heart Association class II or III congestive heart failure were determined after intravenous (IV) treatment (2 mg/kg) and after chronic oral administration (150 mg t.i.d.), either alone or with added furosemide (40 mg b.i.d.). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), filtration fraction, mean arterial pressure (MAP), renal blood flow (RBF), and renal vascular resistance (RVR) were determined each time. Plasma volume (PV) was determined at baseline and after oral enoximone and after oral enoximone plus furosemide. Significant reductions in GFR (18%) and ERPF (20%) were observed after IV treatment but not after oral treatment with or without furosemide. MAP also was lowered significantly by 14% after IV administration but not after oral treatments. PV after oral enoximone plus furosemide was reduced significantly (31%) compared with baseline. These results demonstrate that enoximone produces acute reductions in GFR and ERPF when given intravenously but has no effect on parameters of renal function when given orally, either alone or with furosemide.

Adult↗
PubMed1988

Pharmacokinetics and pharmacodynamics of oral nizatidine.

Nizatidine was studied in six high-acid-secretor (basal secretion, greater than or equal to 5 mEq/hr) male volunteers in a randomized, double-blind, nonbalanced, cross-over, placebo and standard drug-controlled study. Doses of 75 mg, 150 mg, and 300 mg bid were compared with placebo and cimetidine 300 mg qid. Nocturnal acid output was significantly reduced (P less than .01) by all doses of nizatidine (36 +/- 22, 36 +/- 31, and 26 +/- 20 mEq) with 75 mg, 150 mg and 300 mg, respectively, and also by cimetidine (43 +/- 39 mEq) as compared with placebo (101 +/- 61 mEq). Nizatidine also significantly reduced meal-stimulated acid secretion at breakfast (14 +/- 9, 9 +/- 7, and 5 +/- 6 mEq/2 hours with 75 mg, 150 mg, and 300 mg, respectively, P less than .01), at lunch (50 +/- 22, 57 +/- 22 and 50 +/- 35 mEq/2 hours, P less than .05) but did not have any effect at dinner (65 +/- 16, 78 +/- 24, and 71 +/- 17 mEq/2 hours) whereas cimetidine, given every 6 hours, significantly (P less than .01) reduced meal-stimulated acid secretion (25 +/- 16, 27 +/- 20 and 31 +/- 15 mEq/2 hours, breakfast, lunch, and dinner, respectively) as compared with placebo (81 +/- 30, 76 +/- 25, and 66 +/- 16 mEq/2 hours, breakfast, lunch, and dinner, respectively). Both drugs have a similar pharmacokinetic profile. Nizatidine seems to be a promising H2 antagonist, more potent than cimetidine (on an mg/mg basis), and efficacy studies on gastric acid disorders should be performed.

Administration, Oral↗
PubMed1988

An acute dose-response pharmacodynamic evaluation of orally administered isradipine (PN-200-110) in hypertensive patients.

This study was conducted to assess acute oral dose-responses of four dose levels (2.5, 5, 10, 20 mg) of isradipine, a new calcium channel blocking agent of the 1,4-dihydropyridine group. Sixteen patients with mild essential hypertension were investigated using a randomized, four-way cross-over, double-blind, placebo-controlled design. After a 2-week washout period, all patients were admitted to a research unit where they entered a 3-day placebo equilibration, followed by 9 days of double-blind single doses of isradipine. Drug administration was randomized, and baseline blood pressure values obtained preceding active medication doses were fairly constant. Dose-related reductions in supine and in standing blood pressures were obtained. The mean peak supine blood pressure decrements to doses of 2.5, 5, 10, and 20 mg were 17/16, 25/19, 35/22, and 37/25 mm Hg, respectively. Pulse rates increased slightly. Similar responses were obtained with patients in the erect position. Peak hypotensive responses occurred within 3 hours after dosing. The duration of effect persisted as long as 21 hours, particularly after the 10- and 20-mg doses (15/9 and 17/12 mm Hg mean supine blood pressure decrements, respectively).

Antihypertensive Agents↗
PubMed1987

Nabumetone kinetics in the young and elderly.

Nabumetone, a nonsteroidal anti-inflammatory drug of the naphthylalkanone class, was studied in an open-label fashion to compare the relative single-dose and steady-state kinetics in young healthy male volunteers and in elderly patients with degenerative joint disease. Seventeen healthy male volunteers 21 to 30 years of age and 17 patients 60 to 75 years of age were studied. After a single oral dose of 1,000 mg nabumetone, blood and urine samples were collected over a five-day period. Plasma was assayed for nabumetone and the active metabolite, 6-methoxynaphthylacetic acid, and the urine was assayed for five metabolites. Following this phase, they received daily oral doses of 1,000 mg nabumetone for 14 days. After the final dose, blood and urine samples were again collected for five days for the same assays. These data were fitted to a single compartment model and the derived data are as follows: mean maximal plasma concentration, maximal time concentration, area under the plasma-time curve, elimination rate constant, and elimination half-life in the young group after single dose were 22.9, 8.4, 838, 0.032, and 21.2, respectively, whereas on steady-state, values were 33.6, 4.1, 666, 0.031, and 22.1, respectively. In the elderly group after single dose, these values were 30.2, 10.8, 1,538, 0.024, and 29.2, whereas on steady-state, they were 50.0, 7.2, 1,092, 0.027, and 25.6. The accumulation ratio was 1.6 in the young and 1.8 in the elderly. Side effects in the young were mild and consistent of headaches, epigastric discomfort, nausea, and vomiting, whereas in the elderly they consisted mainly of headaches. No significant changes in complete blood cell count, blood chemistries, or urinalysis were noted. We concluded from these data that the drug does not accumulate if given every 24 hours; therefore, a single daily dose should provide sufficient therapy and that due to a difference in elimination, elderly patients may require a lower dose.

Adult↗