Plasma levels of efavirenz and frequency of the CYP2B6 516G>T polymorphism in people living with HIV-1 in Mexico.

Efavirenz (EFV) is a widely used antiretroviral, due to its safety, efficacy, and low cost. However, plasma concentrations have been related with an increased risk of virological failure and the appearance of serious adverse reactions. EFV is metabolized by Cytochrome P450, the main isoenzyme involved is CYP2B6 and the most relevant genetic polymorphisms found in several populations has been the CYP2B6 516G> T. The aim of this study was to identify the frequency of the CYP2B6 516G>T polymorphism and its effect on the plasma concentration of efavirenz (EFV) in a group of people living with HIV (PLWH) and undergoing EFV treatment in Morelos, Mexico. Ninety-six PLWH undergoing EFV treatment, at a daily dose of 600 mg orally in combination with other antiretrovirals (ARVs), were included in this study. The CYP2B6 516G>T polymorphism was detected using PCR-RFLP. The plasma concentrations of EFV were evaluated by high-resolution liquid chromatography coupled to a mass-mass detector, using a protein precipitation method. The median plasma EFV concentration was 4.6 µg/mL (IQR = 4.64) and 64.6% of the subjects had concentrations above the therapeutic range. The CYP2B6 516G>T genotype findings were as follows: 46.9% of the population presented the wild-type genotype (GG), while 45.8 % and 7.3 % showed the heterozygote (GT) and the polymorphic homozygote (TT) genotype, respectively. The homozygote G had the lowest plasma concentrations of EFV (median = 4.1 µg/mL and IQR = 1.7 µg/mL), followed by those with the GT genotype (median = 5.1 µg/mL and IQR = 3.0 µg/mL). Participants with the homozygous T genotype had the highest EFV concentrations (median = 9.7 µg/mL and IQR = 5.8 µg/mL). In conclusion, the CYP2B6 516G>T polymorphism was associated with plasma levels of EFV in PLWH undergoing ARV treatment. EFV plasma concentrations at 600mg doses were outside the therapeutic range in most subjects.

Impacto de un programa piloto de seguimiento farmacoterapéutico sobre el control de la presión arterial de pacientes ambulatorios hipertensos y con síndrome metabólico en México / Impact of a pilot program of medication review with follow-up on the blood pressure control in hypertension ambulatory patients with metabolic syndrome in Mexico

Introducción: En México el 25.5% de los adultos padecen hipertensión arterial sistémica y aproximadamente el 50% de ellos presenta descontrol de la enfermedad. El farmacéutico puede colaborar en el tratamiento de la presión arterial de pacientes hipertensos. Objetivos: Evaluar la mejoría en la presión arterial en pacientes ambulatorios hipertensos con síndrome metabólico mediante un programa piloto de seguimiento farmacoterapéutico Métodos: Se realizó un estudio controlado, aleatorizado y de intervención en pacientes hipertensos y con síndrome metabólico mediante un programa piloto de seguimiento farmacoterapéutico. Se evaluó el control de la presión arterial y el riesgo cardiovascular (RCV) de acuerdo al NCEP-ATP III. Se otorgó seguimiento farmacoterapéutico durante 6 meses, incluyendo educación sanitaria, monitoreo de adherencia, valoración de problemas relacionados con los medicamentos (PRM) y resultados negativos de la medicación (RNM). Se efectuaron mediciones clínicas y de laboratorio para compararse al final de la intervención. Resultados: El promedio de presión arterial sistólica disminuyó en el 16.1% de los participantes del grupo intervención, alcanzándose la meta control de la guía mexicana para hipertensión y del NCEP-ATP III. El RCV en el grupo de intervención y control fue de "bajo riesgo" usando la calculadora PAHO/WHO, y de un rango de 1% a 9.9% usando escala Framingham. La adherencia farmacológica mejoró en el grupo intervención (p=0.021). El promedio de PRM/paciente cambió de 2.5 (DE=1.3) a 0.4 (DE=0.6) al final del estudio (p<0.01). Conclusiones: El seguimiento farmacoterapéutico favoreció el control de la presión arterial en el 16.1% de la población intervenida por el programa piloto

Introduction: In Mexico, 25.5% of adults live with systemic hypertension and approximately 50% of them have poor control of the disease. The pharmacist may collaborate with the medical team in the treatment of blood pressure in hypertensive patients. Objective: To evaluate the blood pressure improvement in outpatients with hypertension and metabolic syndrome through a medication review with follow-up (MRF) pilot program. Methods: It was carried out a randomized, controlled and interventional study in patients with hypertension and metabolic syndrome through a MRF pilot program. Blood pressure control and cardiovascular risk were evaluated using the NCEP-ATP III. A pharmatherapeutical monitoring was provided during 6 months. It included health education, medication adherence monitoring and DRP and NOM assessment. Clinical and laboratory measures were collected and compared at the end of the intervention period with the control group. Results: The systolic blood pressure average diminished in 16.1% of the participants in the intervention group, reaching the control goal of the hypertension Mexican guideline and NCEP-ATP III. The CVR in both groups was "low" using the PAHO/WHO calculator and from 1% to 9.9% using Framingham score. The prevalence of medication adherence increased significantly in the intervention group (p=0.021). The average of DRP/patient changed from 2.5 (SD=1.3) to 0.4, SD=0.6 (p<0.01) at the end of the intervention

Allergen characterization of Chia Seeds (Salvia hispanica), a new allergenic food

No disponible

Pro- and anti-inflammatory cytokines release in mice injected with Crotalus durissus terrificus venom.

The effects of Crotalus durissus terrificus venom (Cdt) were analyzed with respect to the susceptibility and the inflammatory mediators in an experimental model of severe envenomation. BALB/c female mice injected intraperitoneally presented sensibility to Cdt, with changes in specific signs, blood biochemical and inflammatory mediators. The venom induced reduction of glucose and urea levels and an increment of creatinine levels in serum from mice. Significant differences were observed in the time-course of mediator levels in sera from mice injected with Cdt. The maximum levels of IL-6, NO, IL-5, TNF, IL-4 and IL-10 were observed 15 min, 30 min, 1, 2 and 4 hours post-injection, respectively. No difference was observed for levels of IFN-gamma. Taken together, these data indicate that the envenomation by Cdt is regulated both pro- and anti-inflammatory cytokine responses at time-dependent manner. In serum from mice injected with Cdt at the two first hours revealed of pro-inflammatory dominance. However, with an increment of time an increase of anti-inflammatory cytokines was observed and the balance toward to anti-inflammatory dominance. In conclusion, the observation that Cdt affects the production of pro- and anti-inflammatory cytokines provides further evidence for the role played by Cdt in modulating pro/anti-inflammatory cytokine balance.

Evaluation of the quality of four Mexican drug products containing sodium naproxen.

BACKGROUND: There is currently a lot of concern about the quality and therapeutic effectiveness of Mexican pharmaceutical products, and considerable price differences between alternative products containing the same active principle. OBJECTIVE: To establish whether four Mexican drug products, a high price and three lower-cost branded drug products containing sodium naproxen (550 mg immediate release tablets) have equivalent, and consistent pharmaceutical qualities. METHODS: The four products were acquired in Mexico city. Assay for sodium naproxen, content uniformity, disintegration time and dissolution tests were performed according to USP procedures. Drug dissolution profiles were compared using a similarity factor (f(2)). RESULTS AND DISCUSSION: All of the tested products met pharmacopeial quality standards with respect to their active pharmaceutical content and a released drug percentage >70% in 45 min. Lot-to-lot lack of similarity between drug dissolution profiles was observed for two of the products tested. CONCLUSION: There was no significant differences in the quality of the pharmaceutical products tested when judged by the USP pharmaceutical quality standards. However, some differences were observed in the dissolution profiles of the brands tested. Whether these differences are clinically meaningful requires in vivo bioequivalence studies.

Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulation.

AIM: The present investigation was designed to determine the in vivo antidiabetic effect of naringenin (NG) in normoglycaemic and diabetic rat models through blood glucose (GLU) measurements following acute and subchronic time periods. Possible modes of action of NG were investigated and its acute toxicity determined. METHODS: Normoglycaemic and non-insulin-dependent diabetes mellitus (NIDDM) rat models were treated for acute and subchronic (5 days) time periods with 50 mg/kg/day of NG. Blood biochemical profiles were determined after 5 days of the treatment in normoglycaemic and NIDDM rats using commercial kits for GLU, triglycerides (TG), total cholesterol (CHOL) and high-density lipoprotein (HDL). In order to elucidate its antidiabetic mode of action, NG was administered intragastrically and an oral glucose tolerance test performed using GLU and sucrose (2 g/kg) as substrates. The inhibitory effect of a single concentration of NG (10 microM) on 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity in vitro was determined. Finally, the preclinical safety and tolerability of NG was determined by toxicological evaluation in mice and rats using Organization for Economic Cooperation and Development (OECD) protocols. RESULTS: Intragastrically administered NG (50 mg/kg) induced a significant decrease in plasma GLU in normoglycaemic and NIDDM rat models (p < 0.05) following acute and subchronic time periods. After 5 days of administration, NG produced significant diminished blood GLU and TG levels in streptozotocin-nicotinamide-induced diabetic rats. The administration of NG to normal rats significantly increased the levels of TG, CHOL and HDL (p < 0.05). NG (5 and 50 mg/kg) induced a total suppression in the increase of plasma GLU levels after administration of substrates (p < 0.01), but NG did not produce inhibition of alpha-glucosidase activity in vitro. However, NG (10 microM) was shown to inhibit 11beta-HSD1 activity by 39.49% in a cellular enzyme assay. Finally, NG showed a Medium Lethal Dose LD(50) > 5000 mg/kg and ranking at level five based on OECD protocols. CONCLUSION: Our findings suggest that NG may exert its antidiabetic effect by extra-pancreatic action and by suppressing carbohydrate absorption from intestine, thereby reducing the postprandial increase in blood GLU levels.

alpha-Glucosidase inhibitory activity of the methanolic extract from Tournefortia hartwegiana: an anti-hyperglycemic agent.

Tournefortia hartwegiana is a Mexican medicinal plant that is used for the treatment of diabetes, diarrhea and kidney pain. In a previous investigation, the methanolic extract of Tournefortia hartwegiana (METh) showed significant hypoglycemic and anti-diabetic properties on normoglycemic and alloxanized rats. In this context, the purpose of the present study was to establish one of the possible modes of action of METh to induce anti-diabetic activity. METh (310mg/kg) effect on alpha-glucosidase activity was investigated. METh intragastric administration was conducted to determine oral glucose tolerance test (OGTT), using different substrates: glucose, sucrose and maltose. The increase in plasma glucose level was significantly suppressed (P<0.05) by the extract after substrates administration. On the other hand, METh inhibited alpha-glucosidase activity in vitro, in a concentration-dependent manner (IC(50) of 3.16mg/mL). These results suggest that METh might exert its anti-diabetic effect by suppressing carbohydrate absorption from intestine, and thereby reducing the post-prandial increase of blood glucose. On the other hand, the bio-guided fractionation of this extract led to the isolation of: beta-sitosterol (1), stigmasterol (2), lupeol (3), ursolic acid (4), oleanolic acid (5), saccharose (6) and myo-inositol (7), using various chromatographic techniques.