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Biomedical subjects

R Medina

Publications and source records attributed to R Medina.

At least 37 records · Page 2Linked to original sources
PubMed2000

Interaction of CBF alpha/AML/PEBP2 alpha transcription factors with nucleosomes containing promoter sequences requires flexibility in the translational positioning of the histone octamer and exposure of the CBF alpha site.

Chromatin remodeling at eukaryotic gene promoter sequences accompanies transcriptional activation. Both molecular events rely on specific protein-DNA interactions that occur within these promoter sequences. Binding of CBFalpha/AML/PEBP2alpha (core binding factor alpha/acute myelogenous leukemia/polyoma enhancer binding protein 2alpha) proteins is a key event in both tissue-specific and developmentally regulated osteocalcin (OC) promoter activity. To address linkage between chromatin organization and transcription factor binding, we reconstituted segments of the rat OC gene proximal promoter into mononucleosomes and studied binding of CBFalpha proteins. We analyzed binding of bacterially produced Cbfalpha2Alpha and Cbfalpha2B, two splice variants of the human CBFalpha2 gene, and determined the effect of heterodimerization with the Cbfbeta subunit on binding activity. Our results indicate that binding of the truncated Cbfalpha2A protein to naked DNA is independent of Cbfbeta whereas Cbfalpha2A binding to nucleosomal DNA was enhanced by Cbfbeta. In contrast, the Cbfalpha2B interaction with either naked or nucleosomal DNA was strongly dependent on heterodimerization with the Cbfbeta subunit. Additionally, our results demonstrate that both Cbfalpha2A alone and Cbfalpha2B complexed with Cbfbeta can interact with nucleosomal DNA only if there is a degree of flexibility in the positioning of the histone octamer on the DNA fragment and exposure of the CBFalpha site. This situation was achieved with a DNA segment of 182 bp from the rat OC promoter that preferentially positions mononucleosomes upstream of the CBFalpha binding site and leaves this element partially exposed. Taken together, these results suggest that nucleosomal translational positioning is a major determinant of the binding of CBFalpha factors to nucleosomal DNA.

Animals↗
PubMed2000

Bioequivalence study of paracetamol tablets: in vitro-in vivo correlation.

The bioequivalence of three chemically equivalent paracetamol generic Mexican products (500 mg tablets) was evaluated in 12 healthy volunteers using the American innovator product (Tylenol, McNeil, Fort Washington, PA), as the reference. Single oral doses of each product were administered at 1-week intervals using a 4 x 4 Latin square design balanced for the first residual effect. The total amount of paracetamol excreted in urine in 24 hr was taken as a measure of bioavailability. In addition, moment analysis was used to estimate in vitro mean dissolution time (MDT) from dissolution profiles obtained following the USP 23 dissolution test specified for paracetamol tablets and to estimate in vivo mean residence time (MRT) from urinary excretion data. Significant differences in the dissolution performance and in the cumulative amount of paracetamol excreted in urine up to 24 hr were observed when the data were analyzed by analysis of variance (ANOVA) (p < .05). Classical and Westlake 90% confidence limits, as well as the two-sided t test proposed by Schuirmann, and the Anderson-Hauck power analysis supported the final conclusion that only one of the three generic paracetamol products studied can be considered equivalent to the reference product Tylenol. A linear correlation between in vitro MDT and in vivo MRT was found.

Acetaminophen↗
PubMed1998

Photodegradation and phototoxicity studies of furosemide. Involvement of singlet oxygen in the photoinduced hemolysis and lipid peroxidation.

The phototoxic diuretic drug furosemide (1), a 5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)-amino] benzoic acid is photolabile under aerobic and anaerobic conditions. Irradiation of a methanol solution of 1 under oxygen produces photoproducts 2, 3, 4 and singlet oxygen, while under argon the photoproducts 2 and 4 were isolated. A peroxidic unstable photoproduct was detected during the photolysis under oxygen atmosphere. The formation of singlet oxygen by photolysis of 1 was evidenced by trapping with 2,5-dimethylfuran (GC-mass), furfuryl alcohol and 1,3-cyclohexadiene-1,4-diethanoate (HPLC) as 1O2 scavengers and by the histidine test. Furosemide was screened in vitro at different concentrations for UV-Vis-induced phototoxic effects in a photohemolysis test, in the presence and absence of different radical scavengers, singlet oxygen and hydroxyl radical quenchers. However, furosemide photosensitized the peroxidation of linoleic acid, as monitored by the UV-detection of dienic hydroperoxides and it also photosensitized the oxidation of histidine. The photodegradation was catalyzed in the presence of human serum albumin. Studies on peripheral blood mononuclear and polymorphonuclear cells (lymphocytes and neutrophils) demonstrated no phototoxicity on these cell lines.

Dermatitis, Phototoxic↗
PubMed1998

[Factors affecting the trans-endothelial accumulation of atherogenic plasma proteins in artery walls].

Our experiments were done to find out whether there are factors which influence the passage of the two major "risk factor proteins" LDL and fibrinogen, other than their plasma concentrations, from the blood into the arterial walls, where their accumulation is associated with atherogenesis. The results suggest that administration of a remarkable variety of pressor agents over a few days accelerate the uptake of both proteins by arterial walls, and that, in contrast, the process is no faster in rats that have been spontaneously, i.e., genetically, hypertensive for about 3 months. Considering our experimental findings in relation to human atherosclerotic disease, it is interesting that the risk of coronary heart disease and stroke is increased more than additively when both LDL or fibrinogen levels and systolic or diastolic blood pressures are high (18,46). If our work should point to some mechanistic connection between blood pressure and the accumulation of atherogenic plasma proteins in arterial walls, it would provide, at least in principle, an explanation for the epidemiological facts.

Animals↗
PubMed1997

Effect of captopril and losartan on blood pressure and accumulation of LDL and fibrinogen by aortic wall and other tissues in normotensive and hypertensive rats.

Hypertension, low-density lipoprotein (LDL), and fibrinogen are risk factors for atherosclerosis. We investigated the effect of reducing blood pressure, by blocking the renin-angiotensin system (RAS), on the accumulation of these atherogenic proteins in arterial walls and other tissues in conscious, unrestrained, normotensive and hypertensive rats. The accumulation of LDL and fibrinogen, labeled respectively with 125I and 131I via the adduct tyramine cellobiose ([125I]-TC-LDL and [131I]-TC-fibrinogen) was compared in aortic walls, heart, lung, skeletal muscle, liver, kidney, and adrenal gland during the final 24 h of treatment with either the angiotensin-converting enzyme (ACE) inhibitor captopril or the angiotensin II-receptor I (AT1) antagonist losartan. In normotensive rats, the blood pressure was decreased only by losartan. In spontaneously hypertensive rats (SHRs), the blood pressure was decreased by both losartan and captopril. Captopril had no significant effect on the accumulation of LDL or fibrinogen by the aortic wall. Losartan significantly increased the accumulation of LDL by the aortic wall of SHRs. Neither agent produced any change in LDL or fibrinogen accumulation in any of the other tissues. These results indicate that although blocking the RAS at either the enzymic or receptor level produces significant decrease of blood pressure in hypertensive animals, only losartan has any affect on LDL accumulation by the aortic wall.

Angiotensin Receptor Antagonists↗
PubMed1997

Pharmacokinetic study of praziquantel administered alone and in combination with cimetidine in a single-day therapeutic regimen.

A brief therapeutic regimen of praziquantel, reduced to a single day, has been effective for treatment of neurocysticercosis. To study its pharmacokinetic characteristics, levels of praziquantel in plasma were determined for eight healthy volunteers after the administration of three oral doses of 25 mg/kg of body weight given at 2-h intervals, alone and with the simultaneous administration of cimetidine. Each volunteer received both regimens in a randomized crossover design. Blood samples were taken during a period of 12 h, and praziquantel concentration was measured by high-performance liquid chromatography. Levels of praziquantel in plasma remained above 300 ng/ml during a period of 12 h; they increased 100% when cimetidine was jointly administered. Compared with other regimens, the high levels obtained and the longer duration of action seem to be advantageous in prolonging the exposure of the parasites to the drug and support previous clinical experience showing that the treatment of neurocysticercosis with praziquantel can be reduced from 2 weeks to 1 day with the drug still retaining its cysticidal properties. Moreover, simultaneous administration of praziquantel and cimetidine could improve further the efficacy of the single-day therapy for cysticercosis and other parasitic diseases, such as schistosomiasis.

Administration, Oral↗
PubMed1997

Predictors of the rate of renal function decline in non-insulin-dependent diabetes mellitus.

A multivariate analysis of 263 Mexican-American, African-American, and Non-Hispanic white non-insulin-dependent diabetes mellitus patients with end-stage renal disease revealed that in subjects following a linear course of decline of renal function, Mexican-American ethnicity (p = 0.0503) and female sex (p = 0.0036) hasten the rate of decline of renal function, while age (p = 0.0004), hypertension duration (p = 0.0058), and diabetes duration (p = 0.0587) slow the rate of decline of renal function. Blood pressure and glycemic control do not predict the rate of decline. These data suggest that ethnicity and sex-related factors may be as important as blood pressure and glycemic control during the course of non-insulin-dependent diabetic nephropathy.

Age Factors↗
PubMed1996

Localization of the effector-specifying regions of Gi2alpha and Gqalpha.

Heterotrimeric G proteins transmit hormonal and sensory signals received by cell surface receptors to effector proteins that regulate cellular processes. Members of the highly conserved family of alpha subunits specifically modulate the activities of a diverse array of effector proteins. To investigate the determinants of alpha subunit-effector specificity, we localized the effector-specifying regions of alphai2, which inhibits adenylyl cyclase, and alphaq, which stimulates phosphoinositide phospholipase C using chimeric alpha subunits. The chimeras were generated using an in vivo recombination method in Escherichia coli. The effector-specifying regions of both alphai2 and alphaq were localized within the GTPase domain. An alphaq/alphai2/alphaq chimera containing only 78 alphai2 residues within the GTPase domain robustly inhibited adenylyl cyclase. This alphai2 segment includes regions corresponding to two of the three regions of alphas that activate adenylyl cyclase, but does not include any of the alpha subunit regions that switch conformation upon binding GTP. Replacement of the alphaq residues that comprise the helical domain with the homologous alphai2 residues resulted in a chimeric alpha subunit that activated phospholipase C. Combined with previous studies of the effector-specifying residues of alphas and alphat, our results suggest that the effector specificity of alpha subunits is generally determined by the GTPase and not the helical domain.

Adenylyl Cyclase Inhibitors↗
PubMed1996

Effect of water diuresis and water restriction on expression of HSPs-27, -60 and -70 in rat kidney.

Expression of HSP-27, HSP-60 and HSP-70 was estimated in the cortex, outer medulla and inner medulla (papilla) of rats undergoing water diuresis or water restriction for two days. The mRNAs for HSP-27 and HSP-60 in renal papilla were two- to threefold greater in rats during water restriction than in those excreting a dilute urine, but levels of mRNA for HSP-70 were not reduced by water diuresis and Western analysis for HSP-70 protein showed no difference between water-loaded and water-restricted animals.

Animals↗
PubMed1996

Health care access among Mexican Americans with different health insurance coverage.

This study describes the rates of health care access among Mexican Americans with different health insurance coverage. An interview questionnaire was used to collect information regarding sociodemographics, perceived health status, health insurance coverage, and sources of health care from a random sample of 501 Mexican Americans from San Antonio, Texas. Health care access was determined more by having health insurance coverage than by health care needs. Poor Mexican Americans with health insurance had higher health care access rates than did poor Mexican Americans without health insurance. Health care access may improve health care outcomes, but more comprehensive community-based campaigns to promote health and better use of health services in underprivileged populations should be developed.

Adult↗
PubMed1996

Prevention of recurrent esophageal bleeding and survival in patients with alcoholic cirrhosis: a randomized study.

OBJECTIVES: To compare endoscopic sclerotherapy, propranolol and distal splenorenal shunt in the prevention of rebleeding esophageal varices and mortality in alcoholic cirrhotics. METHODS: Forty-three alcoholic cirrhotics that had bled from esophageal varices were randomized to sclerotherapy (13), shunt (15) or propranolol(15). Outcomes measured were rebleeding from varices and death. RESULTS: There was no significant difference between the three treatment groups in relation to rebleeding rate or death. Continued alcohol consumption did not influence outcome. CONCLUSIONS: All three therapies were equally effective in preventing rebleeding from varices.

Adult↗