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Biomedical subjects

R Vargas

Publications and source records attributed to R Vargas.

At least 37 records · Page 2Linked to original sources

Effect of fluticasone propionate aqueous nasal spray versus oral prednisone on the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Fluticasone propionate is a glucocorticoid with negligible oral bioavailability and very low intranasal bioavailability that is used as an intranasal spray for the treatment of rhinitis. OBJECTIVE: The purpose of this study was to evaluate the hypothalamic-pituitary-adrenal (HPA)axis effects of fluticasone propionate aqueous nasal spray (FP ANS) compared with oral prednisone and placebo by using a 6-hour cosyntropin infusion test. METHODS: In a 4-week, randomized, double-blind, double-dummy, placebo-controlled parallel-group study, 105 adult patients with allergic rhinitis were randomly assigned to receive FP ANS 200 microg once daily, FP ANS 400 microg twice daily, oral prednisone 7.5 mg once daily, oral prednisone 15 mg once daily, or placebo. HPA-axis function was assessed at the screening visit and after 4 weeks of treatment by measuring morning plasma cortisol concentrations and poststimulation concentrations of plasma and urinary cortisol. RESULTS: There was no evidence of altered HPA-axis response to cosyntropin by the end of treatment with FP ANS 200 microg once daily or FP ANS 400 microg twice daily when compared with placebo. In contrast, 4 weeks of treatment with oral prednisone 7.5 or 15 mg once daily was associated with significant (p < 0.05 vs placebo) reduction in HPA-axis function, as evidenced by lower plasma cortisol concentrations (area under the plasma concentration-time curve and peak concentrations) after cosyntropin stimulation and reduced mean 24-hour urinary cortisol excretion. FP ANS 400 microg twice daily and both prednisone regimens were associated with a significant (p < 0.05 vs placebo) reduction in mean morning plasma cortisol concentrations. CONCLUSION: These results indicate that a 4-week course of FP ANS at four times the recommended dose does not suppress adrenal function in response to a 6-hour cosyntropin stimulation test.

Administration, Inhalation↗

Antidiarrhoeal activity of Waltheria americana, Commelina coelestis and Alternanthera repens.

The antidiarrhoeal activity of the hexane, chloroform, methanol and aqueous extracts of Waltheria americana, Commelina coelestis and Alternathera repens, was tested on mice with diarrhoea induced by castor oil and MgSO4. The methanol extract of C. coelestis and A. repens and aqueous extract of A. repens, presented antidiarrhoeal effect, monitored by number of liquid feces defecated and intestinal transit of a suspension of graphite with castor oil in Wistar rats.

Administration, Oral↗

An evaluation of the pharmacokinetics of donepezil HCl in patients with impaired hepatic function.

AIM: The aim of this study was to evaluate the pharmacokinetic profile of donepezil HCl (5 mg) in patients with impaired hepatic function, following the administration of single oral doses. METHODS: This was an open-label, non-randomized study comparing the pharmacokinetic profile of donepezil in male volunteers with chronic compensated cirrhosis of the liver (n = 10) to that in healthy age- and sex-matched controls (n = 10). Each subject received a single 5 mg oral dose of donepezil. Blood samples for pharmacokinetic analyses were taken at specified intervals up to 120-h post-dose. Concentrations of donepezil in plasma were determined by HPLC with UV detection. RESULTS: No statistically significant differences in donepezil pharmacokinetics were observed between hepatically impaired patients and normal subjects, with the exception of Cmax. The hepatically impaired patients showed a statistically significant, but not clinically significant, higher mean Cmax value of 6.6 ng ml(-1) compared with the control group, which had a mean Cmax value of 4.8 ng ml(-1) (P=(0.022). This represented an increase of 37.5%. The observed changes in AUC values were smaller and not statistically different. The AUC(0-120) and AUC(0-infinity) were 7% and 21% larger in the hepatically impaired patients than in the normal subjects, respectively, although clearance and volume of distribution were almost identical in the two groups. The t1/2 increased by 20%, but this change was also not statistically significant. Donepezil was equally well tolerated by all subjects. CONCLUSIONS: This study demonstrates that compromised hepatic function does not produce clinically significant changes in the pharmacokinetics of donepezil following single-dose administration. These results suggest that the administration of donepezil to patients with hepatic disease in clinical practice should not require any dosing modifications.

Administration, Oral↗

Endocytosis and MHC class II expression by human oviductal epithelium according to stage of the menstrual cycle.

The epithelium is the first barrier against pathogens invading the lumen of the human oviduct. Its expression of class II major histocompatibility complex (MHC class II) proteins suggests that it might play a role in antigen presentation during the local immune response. To study the role of the oviductal epithelium in antigen processing, its endocytic properties and MHC class II expression were examined. For assay of endocytosis, fluorescein isothiocyanate-labelled bovine serum albumin (BSA-FITC) or Escherichia coli (E. coli-FITC) was infused into the lumen. One-centimetre pieces of oviduct were incubated for 2 h and processed for fluorescence and confocal microscopy, and transmission electron microscopy. Incorporation into secretory and ciliated epithelial cells was observed, which was unrelated to the phase of the menstrual cycle. Small pieces of the organs were frozen and processed for immunohistochemistry. Most oviducts expressed MHC class II (HLA.DR) in the epithelium and in some cases this was coincident with endocytosis, but there was no statistically significant association between this expression and either endocytotic activity or the phase of the menstrual cycle. Results demonstrate that the epithelium of the human oviduct exhibits endocytic properties towards luminal soluble and particle antigens, which is not related either to MHC class II expression or to the phase of the menstrual cycle.

Adult↗

Metoclopramide enhances labetalol-induced antihypertensive effect during handgrip in hypertensive patients.

The effects of metoclopramide, labetalol, and metoclopramide plus labetalol treatments on baseline cardiovascular parameters and isometric handgrip-induced changes were evaluated in 11 hypertensive subjects. Although all treatments were effective in reducing resting systolic (SBP) and diastolic (DBP) blood pressures, the combination of metoclopramide and labetalol appeared to provide a greater decrease (changes in SBP/DBP: 15/11 mm Hg, P < 0.05; from 149 +/- 4/95 +/- 4 mm Hg to 134 +/- 5/84 +/- 3 mm Hg) than did labetalol alone (changes in SBP/DBP: 10/9 mm Hg, P < 0.05; from 149 +/- 4/95 +/- 4 to 139 +/- 4/86 +/- 3 mm Hg). At 2 minutes, handgrip increased blood pressure on placebo (changes in SBP/DBP: 34/7 mm Hg, P < 0. 001). In the presence of metoclopramide and metoclopramide plus labetalol, however, handgrip induced lesser increases in blood pressure (changes in SBP/DBP: 23/7 mm Hg, P < 0.01, and 18/4 mm Hg, P < 0.01, for metoclopramide and metoclopramide plus labetalol treatments). We conclude that (1) metoclopramide lowers blood pressure in hypertensive patients; (2) metoclopramide attenuates blood pressure response to isometric handgrip; and (3) both compounds, labetalol and metoclopramide, seem to have a pharmacologic interaction concerning blood pressure decrease. A clinical significance is suggested for the metoclopramide effect.

Antihypertensive Agents↗

Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype.

X-linked nephrogenic diabetes insipidus (NDI) is a rare disease with defective renal and extrarenal arginine vasopressin V2 receptor responses due to mutations in the AVPR2 gene in Xq28. To study the cause of loss of function of mutant V2 receptors, we expressed 12 mutations (N55H, L59P, L83Q, V88M, 497CC-->GG, deltaR202, I209F, 700delC, 908insT, A294P, P322H, P322S) in COS-7 cells. Eleven of these, including P322H, were characterized by a complete loss of function, but the mutation P322S demonstrated a mild clinical and in vitro phenotype. This was characterized by a late diagnosis without any growth or developmental delay and a significant increase in urine osmolality after intravenous 1-deamino[D-Arg8]AVP administration. In vitro, the P322S mutant was able to partially activate the Gs/adenylyl cyclase system in contrast to the other V2R mutants including P322H, which were completely inactive in this regard. This showed not only that Pro 322 is important for proper V2R coupling, but also that the degree of impairment is strongly dependent on the identity of the substituting amino acid. Three-dimensional modeling of the P322H and P322S mutant receptors suggested that the complete loss of function of the P322H receptor could be due, in part, to hydrogen bond formation between the His 322 side chain and the carboxyl group of Asp 85, which does not occur in the P322S receptor.

Blotting, Western↗

Coyolosa, a new hypoglycemic from Acrocomia mexicana.

From the methanol extract of the Arocomia mexicana root a new tetrahydropyrane compound was isolated. Its skeletal structure and relative stereochemistry were established by spectral analysis. Substituent effects have been determined with the hope of providing information about steric interactions and conformation of tetrahydropyran derivatives and carbohydrates. The extract showed a significant blood sugar lowering effect on normal and alloxan-diabetic mice when administered at 2.5 to 40 mg/kg i.p. doses, and exhibited a dose-dependent response in the mice models.

Animals↗

Angiopeptin inhibits thymidine incorporation by explants of porcine coronary arteries.

Angiopeptin, a stable octapeptide analog of somatostatin, inhibits proliferation in a variety of cancer cell lines. We studied the effect of angiopeptin on 3H-thymidine uptake into ring segments from the porcine coronary tree. The incorporation of 3H-thymidine into segments of porcine left anterior descending (LAD) coronary artery was time dependent and reached a plateau after 48 h. The addition of angiopeptin (48.1 and 96.2 nM) to the culture medium significantly inhibited 3H-thymidine incorporation into the segments by 36.7 +/- 10.1% and 48.3 +/- 2.3% of the control, respectively. Forskolin (100 microM), inhibited 3H-thymidine incorporation (52.7 +/- 10.1%) to the same degree as did angiopeptin (96.2 nM). Incubation of the segments with 125I-labeled angiopeptin, for 2 h at 37 degrees C, showed angiopeptin uptake to be time dependent and exhibited a first-order kinetics, reaching equilibrium after 30 min. Autoradiographic studies showed a uniform distribution of angiopeptin within the endothelium, media, and adventitia. Most of the labeling was associated with the nuclei of the cells. Angiopeptin, after 30-min incubation, did not significantly modify the basal levels of cyclic adenosine monophosphate (cAMP). In contrast, forskolin (100 microM) elicited a 50-fold increase of the basal levels of cAMP. These results indicate that in addition to its endocrine effects, angiopeptin reduces the rate of proliferation by acting directly on the vessel wall.

Animals↗

A common NKCC2 mutation in Costa Rican Bartter's syndrome patients: evidence for a founder effect.

Bartter's syndrome involves an overlapping set of closely related renal tubular disorders that can be subdivided into at least three clinical phenotypes: (1) the hypercalciuric antenatal Bartter variant; (2) the classic Bartter variant; and (3) the hypocalciuric-hypomagnesemic Gitelman variant. Recent data demonstrate that in several phenotypically indistinguishable cohorts, antenatal Bartter's syndrome is genetically heterogeneous. In these patients, mutations in the genes encoding either the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the ATP-regulated potassium channel ROMK (KCNJI) have been identified. A cohort of 20 Costa Rican patients with a congenital syndrome that bears strong similarities to antenatal Bartter's syndrome but also has several distinct features has recently been described. In this cohort, we have identified a predominant mutation that introduces a premature stop in codon W625 of the NKCC2 gene (SCL12A1). This mutant allele is contained on a single common haplotype, suggesting that the majority of antenatal Bartter's syndrome patients in Costa Rica share a single common ancestor.

Adult↗

Using a knowledge, attitudes and practices survey to supplement findings of an outbreak investigation: cholera prevention measures during the 1991 epidemic in Peru.

BACKGROUND: To assess the effectiveness of the cholera prevention activities of the Peruvian Ministry of Health, we conducted a knowledge, attitudes, and practices (KAP) survey in urban and rural Amazon communities during the cholera epidemic in 1991. METHODS: We surveyed heads of 67 urban and 61 rural households to determine diarrhoea rates, sources of cholera prevention information, and knowledge, attitudes, and practices regarding ten cholera prevention measures. RESULTS: Twenty-five per cent of 482 urban and 11% of 454 rural household members had diarrhoea during the first 3-4 months of the epidemic. Exposure to mass media education was greater in urban areas, and education through interpersonal communication was more prevalent in rural villages. Ninety-three per cent of rural and 67% of urban respondents believed they could prevent cholera. The mean numbers of correct responses to ten knowledge questions were 7.8 for urban and 8.2 for rural respondents. Practices lagged behind knowledge and attitudes (mean correct response to ten possible: urban 4.9, rural 4.6). Seventy-five per cent of respondents drank untreated water and 91% ate unwashed produce, both of which were identified as cholera risk factors in a concurrently conducted case-control study. CONCLUSIONS: The cholera prevention campaign successfully educated respondents, but did not cause many to adopt preventive behaviours. Direct interpersonal education by community-based personnel may enhance the likelihood of translating education into changes in health behaviours. Knowledge, attitudes, and practices surveys conducted with case-control studies during an epidemic can be an effective method of refining education/control programmes.

Adolescent↗

Estradiol effect on rate of proliferation of rat carotid segments: effect of gender and tamoxifen.

Using organ culture of carotid artery segments from sexually mature male and female rats, we examined the effect of estradiol 17 beta on proliferation. The index of cell proliferation was [3H]thymidine uptake. Estradiol 17 beta (0.18-0.36 microM) inhibited the uptake of thymidine in a concentration-dependent manner (p < 0.05). Estradiol 17 beta inhibited [3H]thymidine uptake only in the absence of the weak estrogen receptor agonist phenol red and in carotid artery segments from sexually mature female (p < 0.01) but not male rats. Tamoxifen (0.1 and 1 microM), a partial agonist of estrogen receptors, significantly inhibited thymidine uptake (p < 0.01). However, preincubation of the segments with tamoxifen (0.1 and 1.0 microM) for 4 h before the exposure to estradiol, blocked estradiol 17 beta-induced inhibition of thymidine uptake (p < 0.05 and p < 0.01 for 0.1 and 1.0 microM, respectively). The cyclooxygenase inhibitor indomethacin (5 microM) did not affect either the basal [3H]thymidine uptake or the estradiol 17 beta-induced inhibition of that uptake. This latter finding suggests that prostacyclin or prostaglandin E2 does not mediate the inhibitory response to estradiol 17 beta. The results of these experiments suggest that estradiol 17 beta-induced inhibition of proliferation of rat carotid artery segments is mediated through activation of estrogen receptors.

Animals↗

Estradiol increases cyclic adenosine monophosphate in rat pulmonary vascular smooth muscle cells by a nongenomic mechanism.

Estrogen, like other steroids, may induce rapid nongenomic cellular effects. We studied the effect on intracellular cAMP of short-term exposure (5 min) of cultured rat pulmonary vascular smooth muscle cells (VSMC) to estradiol 17 beta. At confluence, VSMC were incubated in phosphate buffer saline for 1 hr before exposure to different hormones. The reaction was stopped with 0.1 N HCl and cyclic adenosine monophosphate (cAMP) was measured by radioimmunoassay. The 5-min incubation with estradiol 17 beta (0.3-30 microM) significantly increased basal intracellular cAMP in a concentration-dependent manner. The stimulatory effect of estradiol on cAMP was time-dependent, increasing with prolonged exposure to the hormone, and was not affected by the protein synthesis inhibitor, actinomycin D (5 micrograms/ml), at 5 and 30 min. Comparable concentrations of testosterone or estradiol 17 alpha had no significant effect on cAMP. The estrogen receptor partial agonist, tamoxifen also significantly increased basal cAMP in a concentration-dependent manner, but inhibited the effect of estradiol. Furthermore, forskolin elicited a concentration-dependent increase in cAMP (396.6 +/- 53% at 10 microM concentration), which was significantly potentiated in presence of estradiol. The effect of estradiol is unlikely to be mediated by G-protein activation, because the G protein inhibitor, pertussis toxin (100 ng/ml), did not significantly affect estradiol-induced increase in cAMP. Removal of Ca++ from the incubation medium inhibited the stimulatory effect of estradiol 17 beta suggesting that estradiol may increase pulmonary VSMC cAMP via a Ca(++)-dependent pathway. We suggest that the effect of estradiol 17 beta in these experiments is nongenomic in nature, and is possibly mediated by direct interaction of the hormone with specific membrane binding sites.

Animals↗

Investigation of rabies virus strains in Mexico with a panel of monoclonal antibodies used to classify Lyssavirus.

The purpose of this study was to evaluate the ability of a panel of eight antinucleocapsid monoclonal antibodies developed in Europe to assess rabies virus strains isolated from various animal species in geographically diverse areas of Mexico. Fifty-one rabies-positive brain tissue samples from animals and humans were examined. Material from these samples was used to infect mice, whose brain tissue was subsequently tested by indirect immunofluorescence using the monoclonal antibodies described above. The study did not turn up any strong evidence of Lyssavirus other than rabies virus, but did find four antigenic variants differing from the classic rabies virus serotype. Samples of these latter were sent to the Pasteur Institute in Paris for confirmation. Overall, the antibody panel was deemed useful for rapid typing of rabies virus in Mexico. It also appears possible that autochthonous antigenic variations are now appearing in strains of the virus found in Mexico, which could explain some of the failures observed with certain vaccines. These circumstances appear to create a need for producing antinucleocapsid monoclonal antibodies with strains of rabies virus indigenous to the area.

Animals↗

Annotated list of species of marine crustaceans (Decapoda and Stomatopoda) from Golfo Dulce, Costa Rica.

The present study is an annotated list of the marine crustaceans (Decapoda and Stomatopoda) from Golfo Dulce, Costa Rica, collected during the RV Victor Hensen Cruise 1993-1994, at depths ranging from 20 to 260 m. Stomatopoda was represented by one family and two species. Decapoda was represented by 12 families and 21 species. Two new records for Costa Rica, Cancer johngarthi and Lysmata californica are reported. This increases the reported marine crustaceans of Golfo Dulce to three species of Stomatopoda and sixty-six of Decapoda (a complete checklist in included). A list of species reported in the literature from the gulf is also included.

Animals↗