Combined administration of gallic acid and glibenclamide mitigate systemic complication and histological changes in the cornea of diabetic rats induced with streptozotocin

Purpose: To determine the effect of gallic acid or its combination with glibenclamide on some biochemical markers and histology of the cornea of streptozotocin (STZ) induced diabetic rats. Methods: Following induction of diabetes, 24 male albino rats were divided into four groups of six rats each. Groups 1 and 2 (control and diabetic) received rat pellets and distilled water; group 3 (gallic acid) received rat pellets and gallic acid (10 mg/kg, orally) dissolved in the distilled water; and group 4 (gallic acid + glibenclamide) received rat pellets, gallic acid (10 mg/kg, orally), and glibenclamide (5 mg/kg, orally) dissolved in the distilled water. The treatments were administered for three months after which the rats were sacrificed after an overnight fast. Blood and sera were collected for the determination of biochemical parameters, while their eyes were excised for histology. Results: STZ administration to the rats induced insulin resistance, hyperglycemia, microprotenuria, loss of weight, oxidative stress, inflammation, and alteration of their cornea histology, which was abolished following supplementation with gallic acid or its combination with glibenclamide. Conclusions: The study showed the potentials of gallic acid and glibenclamide in mitigating systemic complication and histological changes in the cornea of diabetic rats induced with STZ.

Metformin versus glyburide in treatment and control of gestational diabetes mellitus: a systematic review with meta-analysis

ABSTRACT Objective To compare the major outcomes of use of metformin and glyburide in treatment of gestational diabetes mellitus. Methods Studies published in English, in the last 10 years, in the databases MEDLINE®, SciELO, LILACS and Cochrane Library were analyzed, and randomized controlled trials were selected. Health Sciences Descriptors were used to compose the search phrase, and the keywords "Gestational diabetes", "Glyburide", "Metformin" and their variations were searched in the Medical Subject Headings. PRISMA systematization was used to prepare this review, and a meta-analysis was conducted aiming to mathematically show the results of fasting blood glucose, postprandial blood glucose, birth weight and weight gain during pregnancy after using metformin and glyburide. Results The studies evaluated birth weight, neonatal hypoglycemia, mode of delivery, need for intensive care, Apgar score, macrosomia, fasting glucose, postprandial glucose and weight gain during pregnancy. In 60% of studies, there were no statistically significant differences regarding safety and efficacy of administration of metformin and glyburide. Meta-analysis demonstrated the absence of statistical differences between these drugs in fasting blood glucose (p=0.821), postprandial blood glucose (p=0.217) and birth weight (p=0.194). However, significant differences were shown in weight gain during pregnancy (p=0.036). Conclusion The methods are effective, but the adverse effects of glyburide are more common; therefore, the use of metformin should be recommended, if in monotherapy.

Antidiabéticos orais no diabetes gestacional: revisão de literatura / Oral antidiabetics in gestational diabetes: literature review

O diabetes mellitus gestacional (DMG) é um distúrbio metabólico por déficit na produção e/ou ação insulínica. Tem relação direta com um constante estado catabólico associado com maior resistência à ação da insulina. Doença de difícil controle, implica risco materno-fetal elevado. O objetivo é estudar a eficácia das drogas antidiabéticas orais sobre o controle glicêmico no DMG e sua segurança quanto aos desfechos gestacionais e perinatais. Trata-se de revisão de literatura descritiva baseada em dados de artigos, livros-texto e guidelines emitidos nos últimos cinco anos. O antidiabético oral pode ser uma boa alternativa no controle do DMG em fase inicial da doença, na presença de distúrbio metabólico e como complemento da terapia com insulina. Entretanto, por causa de sua passagem placentária, há preocupações com seus efeitos fetais e perinatais. Estudos comparativos destacam a metformina no manejo do DMG, considerando principalmente a segurança materno-fetal.(AU)

Gestational diabetes mellitus (GDM) is a metabolic disorder caused by deficit in production and/or insulin action. It is directly related to a constant catabolic state associated with greater resistance to insulin action. Disease difficult to control, implies high maternal-fetal risk. To study the efficacy of oral antidiabetic drugs on glycemic control in GDM and its safety regarding gestational and perinatal outcomes. Descriptive literature review based on data from articles, textbooks and guidelines issued in the last five years. Oral antidiabetic can be a good alternative in the control of GDM in the initial phase of the disease, in the presence of metabolic disorder and as a complement to insulin therapy. However, there are concerns about its placental passage and perinatal effects. Comparative studies highlight metformin in the management of DMG considering mainly maternal-fetal safety.(AU)

Tratamento para o diabetes mellitus gestacional: uma revisão de literatura / Treatment for gestational diabetes mellitus: a literature review

O diabetes mellitus gestacional (DMG) é uma complicação que atinge o metabolismo da gestante, resultando em intolerância à glicose e consequente hiperglicemia, originada pela insuficiência de insulina materna. Este estudo tem como objetivo identificar os tratamentos disponíveis e mais utilizados para o DMG. Trata-se de um uma revisão de literatura, feita a partir de 22 referências, acerca dos tratamentos para o DMG. As bases de dados escolhidas foram Google Acadêmico, UpToDate, SciELO e o acervo da Universidade do Planalto Catarinense. Estudos apontam a insulina humana ­ NPH e regular ­ como a principal escolha, quando comparada aos seus análogos, apesar de ainda existirem muitas controvérsias quanto ao início do tratamento, o esquema terapêutico e os ajustes das doses. Pesquisas têm demonstrado bons resultados sobre a eficácia e a segurança dos hipoglicemiantes orais ­ gliburida e metformina ­ no tratamento de gestantes diabéticas, mas é evidente a necessidade de mais estudos para confirmar a efetividade deles e garantir um bom desenvolvimento do concepto. Concluiu-se que o controle dietético e o exercício físico são a primeira opção de tratamento para o DMG. Todavia, caso a euglicemia não seja atingida, opta-se pelo tratamento medicamentoso por meio da insulinoterapia ou hipoglicemiantes orais, o que possibilita a redução da incidência dos efeitos adversos ao binômio materno-fetal.(AU)

Gestational diabetes mellitus (DMG) is a complication that affects the pregnant woman's metabolism, resulting in glucose intolerance and consequent hyperglycemia, caused by insufficient maternal insulin. This study aims to identify the available and most used treatments for DMG. This is a literature review, based on 22 references, about treatments for Gestational Diabetes; the databases chosen were Google Scholar, UpToDate, SciELO and the collection of the Universidade do Planalto Catarinense. Studies point to human insulin ­ NPH and regular ­ as the main choice when compared to its analogues, although there are still many controversies about the beginning of treatment, therapeutic scheme and dose adjustments. Researches have shown good results on the efficacy and safety of oral hypoglycemic agents ­ glyburide and metformin ­ in the treatment of diabetic pregnant women, but it is evident the need for further studies to confirm their effectiveness and to guarantee a good development of the fetus. It was concluded that dietary control and physical exercise are the first treatment option for DGM. However, if euglycemia is not achieved, drug treatment is chosen through insulin therapy or oral hypoglycemic agents, which makes it possible to reduce the incidence of adverse effects to the maternal-fetal binomial.(AU)

Exposição crônica ao cloridrato de metformina e à glibenclamida causa alterações comportamentais, glicêmicas e de mortalidade em Hemigrammus caudovittatus e Danio rerio / Chronic exposure to metformin chloridrate and glibenclamide causes behavioral, blood glucose and mortality changes of Hemigrammus caudovittatus and Danio rerio

Hemigrammus caudovittatus e Danio rerio foram expostos aos hipoglicemiantes orais (HOs) cloridrato de metformina a 40µg/L e 120µg/L e glibenclamida a 0,13µg/L e 0,39µg/L durante 100 dias. Foram avaliados os efeitos tóxicos dos fármacos em relação ao peso, ao comportamento animal, à glicemia e à mortalidade. H. caudovittatus expostos à menor concentração dos fármacos apresentaram aumento significativo (P<0,05) no evento Respiração Aérea. Ainda, foi observado aumento no comportamento Descansar quando os animais foram expostos à glibenclamida a 0,39µg/L. Em D. rerio expostos ao cloridrato de metformina a 120µg/L, foi observado aumento (P<0,05) no comportamento Descansar. A glibenclamida provocou redução (P<0,05) na glicemia de H. caudovittatus. Ambos os fármacos causaram efeito letal na espécie D. rerio, contudo a glibenclamida foi mais tóxica, causando 100% de mortalidade em 30 dias de exposição. Os animais que vieram a óbito apresentaram congestão nos arcos branquiais e hemorragia. Os HOs foram desenvolvidos para apresentarem efeitos fisiológicos em mamíferos, entretanto efeitos tóxicos foram encontrados nas duas espécies de peixe estudadas. Isso levanta a preocupação sobre possíveis efeitos tóxicos de HOs e sobre quais métodos serão utilizados para a sua degradação no ambiente aquático.(AU)

Hemigrammus caudovittatus and Danio rerio were exposed to oral hypoglycemic drugs (HOs) metformin hydrochloride at 40µg/L and 120µg/L and to glibenclamide at 0.13µg/L and 0.39µg/L during 100 days. Toxic effects of the drugs were evaluated based on weight, animal behavior, blood glucose and mortality. H. caudovittatus exposed to lowest concentration of the drugs showed significant increase (P< 0.05) in the Air breathing event. Furthermore, increase in Rest event was observed when animals were exposed to glibenclamide at 0.39µg/L. An increase (P< 0.05) in the frequency of Rest behavior in the D. rerio exposed to metformin hydrochloride at 120µg/L was observed. Glibenclamide caused decrease (P< 0.05) in the blood glucose of H. caudovittatus. Both drugs caused lethal effect against D. rerio. Nevertheless, glibenclamide was more toxic causing 100% of mortality after 30 days of exposure. The animals that died showed congestion on the branchial arches and hemorrhage. The HOs were developed to have physiological effects in mammals. However, toxic effects were found in both species of fish studied. This raises concerns about possible toxic effects of HOs and what methods will be used for their degradation in the aquatic environment.(AU)

Caracterización clínica epidemiológica de la diabetes mellitus en dos áreas de salud. Municipio Cárdenas. 2017 / Clinico-epidemiological characterization of diabetes mellitus in two health areas. Municipality of Cardenas. 2017

RESUMEN Introducción: la diabetes mellitus es un trastorno metabólico caracterizado por hiperglucemia crónica con alteraciones en los carbohidratos, grasas y proteínas. Las tasas de morbimortalidad han aumentado al igual que la obesidad, constituye un problema de salud en el mundo, Cuba y la provincia de Matanzas. Objetivo: realizar una caracterización clínica epidemiológica de la diabetes mellitus tipo 2 en dos áreas de salud, conocer las variables e identificar las barreras para una posterior intervención. Materiales y métodos: se realizó un estudio epidemiológico descriptivo- transversal a 750 diabéticos tipo 2 mayores de 18 años en dos áreas de salud. Se realizaron encuestas, procesándose en el programa Epi-Info, obteniéndose la frecuencia de las variables, y las diferencias estadísticas significativas entre variables de las dos aéreas de salud, utilizándose el valor de p < 0,05 % y el Chi2. Resultados: el promedio de edad fue de 62,2 años, predominio del sexo femenino y color de la piel blanca. La hipertensión arterial y la obesidad fueron las enfermedades más asociadas, y el tabaquismo, la ingestión de bebidas alcohólicas y azucaradas, y la no realización de ejercicios físicos fueron los factores asociados más relevantes. Los medicamentos más utilizados fueron la glibenclamida y la metformina. Conclusiones: la diabetes mellitus es la primera causa de fracaso renal en el mundo occidental, siendo la insuficiencia renal una de las complicaciones crónicas más graves de esta enfermedad. Entre las principales causas de muerte de esta enfermedad son las complicaciones macrovasculares, manifestadas clínicamente como cardiopatía isquémica, insuficiencia cardíaca, la enfermedad vascular cerebral y la insuficiencia arterial periférica.

ABSTRACT Introduction: diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia with alterations in carbohydrates, fats and proteins. Morbi-mortality rates have increased as have done obesity, being a health problem in the world, Cuba and the province of Matanzas. Objective: to carry out clinical-epidemiological characterization of type 2 diabetes mellitus in two health areas, knowing the variables and identifying the barriers for a subsequent intervention. Materials and methods: a cross-sectional descriptive study was carried out in 750 type-2 diabetic patients over 18 years in two health areas. Surveys were made and processed in Epi-Info program, showing significant statistic differences among variables of both health areas; p < 0,05 % value and Chi2 were used. Results: the average age was 62.2 years, predominating female sex and white skin color. The most commonly associated diseases were arterial hypertension and obesity; smoking and drinking alcoholic and sugar-sweetened beverages and sedentary life were the most relevant associated factors. The most commonly used medications were glibenclamide and metformin. Conclusions: diabetes is the first cause of renal failure in the Western world, being renal insufficiency one of the most serious chronic complications of this disease. The main causes of death of this disease are macro vascular complications clinically manifested as ischemic heart disease, heart failure, cerebra-vascular disease and peripheral arterial insufficiency.

Granuloma anular, pronóstico de diabetes mellitus. A propósito de un caso / Annular granuloma, prognosis of diabetes mellitus. On the purpose of a case

RESUMEN El granuloma anular es una dermatosis de relativa frecuencia en niños, jóvenes y adultos. Está caracterizado por lesiones cutáneas eritemato-pápulo-nodulares, que adoptan una disposición anular. Su etiopatogenia es desconocida, pero con numerosos factores predisponentes, desencadenantes o asociados a ella; como es la diabetes mellitus y/o procesos neoplásicos o paraneoplásicos. Resulta importante el estudio de pacientes con este diagnóstico por su asociación con entidades como las antes mencionadas. Se realizó el reporte de un caso en adulto mayor de 65 años, con diagnóstico de granuloma anular, diabetes mellitus y neoplasia de páncreas.

ABSTRACT Annular granuloma is a dermatosis relatively frequent in children, young and adult people. It is characterized by erythematous-papular-nodular skin lesions adopting annular disposition. Its etio-pathogenesis is unknown, but there are many predisposal, unleashing factors, or associated to this disease, like diabetes mellitus and/or neoplastic or paraneoplastic processes. It is important to study the patients diagnosed with the disease due to its association with entities like those before mentioned. The reported case is the case of a patient elder than 65 years, diagnosed with annular granuloma, diabetes mellitus and pancreas neoplasia.

Modulatory effect of baicalein on gene expression and activity of antioxidant enzymes in streptozotocin-nicotinamide induced diabetic rats

Oxidative stress plays the central role in the pathogenesis and progression of diabetic complications. The present study aims to investigate the beneficial effect of oral administration of flavone baicalein in streptozotocin-nicotinamide (STZ-NA) induced diabetic rats by measuring oxidative stress markers, antioxidant enzyme activities and expression analysis of antioxidant genes. Experimental diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (55 mg /kg b.wt), 15 min after the i.p. administration of NA. At the end of the experimental period, thiobarbituric acid reactive substances (TBARS), activities of antioxidant enzymes and expression levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) were measured in diabetic rats along with serum biochemical parameters namely total cholesterol (TC), total triglyceride (TG), aspartate transaminase (AST) alanine transaminase (ALT) and glycosylated hemoglobin (HbA1c). Oral administration of baicalein (40 mg/kg b.wt/day) demonstrated a significant ameliorative effect on all studied biochemical and oxidative stress parameters. Biochemical findings were corroborated by qPCR expression analysis which showed significant upregulation of antioxidant genes in diabetic rats. These results suggest that baicalein supplementation may reduce diabetes and its complications by suppressing oxidative stress and enhancing gene expression and antioxidant enzyme activities in diabetic rats.

TeleCondutas: diabetes e gestação / TeleGuides: diabetes and gestation

Os quadros hiperglicêmicos que são diagnosticados na gravidez são classificados pela Organização Mundial da Saúde (OMS) em duas categorias: 1) "Diabetes Mellitus (DM) na gestação": hiperglicemia compatível com DM fora na gestação, mas que o diagnóstico é feito na gestação (overt Diabetes em inglês) e; 2) "Diabetes Mellitus Gestacional" (DMG): estado de hiperglicemia, em valores que não preenchem critérios para DM, usualmente diagnosticado após a metade da gestação e que tende a se resolver com o término da gestação. No Brasil, a prevalência de DMG no Sistema Único de Saúde (SUS) passou de 7,5% para 18%, conforme os critérios diagnósticos atuais. Tanto o DM na gestação quanto o DMG aumentam o risco de desfechos maternos e fetais graves, devendo, portanto, ser identificados, adequadamente tratados na Atenção Primária à Saúde (APS) e, quando indicado, nos serviços especializados em Pré-natal de alto risco. Esta guia apresenta informação que orienta a conduta para casos de diabetes e gestação no contexto da Atenção Primária à Saúde, incluindo: fatores de risco para dmg, classificação, rastreamento, tratamento dm gestacional, tratamento dm na gestação, controle glicêmico, avaliação pré-concepcional em diabéticas, avaliação complementar, momento e via de parto, acompanhamento pós-parto, encaminhamento para serviço especializado, referências anexo 1 - orientações nutricionais.

Seguridad cardiovascular de los antidiabéticos orales / Cardiovascular safety of oral antidiabetics

Resumen La Diabetes Mellitus tipo 2 (DM-2) es un equivalente de riesgo cardiovascular. Existe una gran variedad de fármacos para el control de la glicemia en los pacientes con DM-2, los cuales tienen diferencias en su perfil cardiovascular, unos han demostrado un beneficio en la reducción de riesgo de eventos cardiovasculares, otros tienen un efecto neutro, y en el caso de otros fármacos como las sulfonilureas y las tiazolinedionas existe dudas sobre su seguridad cardiovascular. Sien do DM-2 un equivalente de riesgo coronario, es fundamental tomar en cuenta el perfil de riesgo cardiovascular de estos medicamentos a la hora de iniciar alguna de estas drogas y no solo su eficacia para controlar los niveles de glicemia. El objetivo de esta revisión es comentar sobre los estudios más recientes que evalúan el riesgo cardiovascular con el uso de los distintos antidiabéticos orales.

Abstract Cardiovascular Safety of Oral Antidiabetics Diabetes Mellitus type 2 (DM-2) is an equivalent of cardiovascular risk. There is a wide variety of drugs for the glycemic control in patients with DM-2, which have differences in their cardiovascular profile, some have shown a benefit in reducing the risk of cardiovascular events, others have a neutral effect, and in the case of other drugs such as sulfonylurea and thiazolidinedione, there are doubts about their cardiovascular safety. Being DM-2 an equivalent of coronary risk, it is essential to consider the cardiovascular risk profile of these medicines when starting any of these drugs and not only their effectiveness in controlling glycaemia levels. The objective of this review is to comment on the most recent studies evaluating cardiovascular risk with the use of different oral antidiabetics.

Evaluación de la prescripción de glibenclamida en diabéticos tipo 2 / Evaluation of glibenclamide prescription in type 2 diabetic patients

RESUMEN Introducción: Las sulfonilureas permanecen junto con la metformina como el tratamiento farmacológico más usado para los pacientes diabéticos tipo 2, y continúan siendo los antidiabéticos más prescritos en algunas regiones del mundo. Objetivo: Evaluar la prescripción de glibenclamida en aspectos relacionados a contraindicaciones, dosificación, y prevención de efectos adversos, en el tratamiento de los pacientes diabéticos tipo 2 que acuden a una institución de salud de baja complejidad en Cartagena de Indias, Colombia. Metodología: Estudio descriptivo con enfoque desde la fármaco-epidemiología dirigido específicamente al campo de los estudios de utilización de medicamentos, basado en los datos recogidos mediante revisión de historias clínicas de 331 pacientes diabéticos tipo 2, mayores de 18 años en un centro de atención primaria en salud de la ciudad de Cartagena de Indias entre los años 2013 y 2014. Se estudiaron variables demográficas, clínicas y paraclínicas, el esquema terapéutico y la calidad de la prescripción. La información se analizó usando estadística descriptiva. Resultados: 57 % (189) de los pacientes utilizaron glibenclamida siendo un 59.3 % (153) prescrito de manera inadecuada, 45.5% (86) tenían alguna contraindicación para el empleo del medicamento. En 1 % de los pacientes de la muestra se prescribió sobrepasando el rango de dosis terapéutica Conclusiones: La calidad de la prescripción de la glibenclamida fue inadecuada en una proporción importante de pacientes, se hace necesario implementar estrategias educacionales que capaciten al personal médico para una correcta utilización de los fármacos antidiabéticos. La glibenclamida comparada con otras sulfonilureas de segunda generación nos brinda más desventajas que ventajas.

ABSTRACT Introduction: Sulfonylureas remain with metformin as the most used drug treatment for type 2 diabetic patients and remain the most prescribed anti-diabetic in some regions of the world. Target: Evaluate prescribing glyburide in aspects related to contraindications, dosage, and prevention of adverse effects, in the treatment of type 2 diabetic patients attending a health institution low complexity in Cartagena de Indias, Colombia. Methodology: Descriptive study with approach from the pharmaco-epidemiology specifically directed to the field of studies of drug use, based on the data collected through review of medical records of 331 type 2 diabetic patients over 18 years in a primary health care in the city of Cartagena de Indias between 2013 and 2014. demographic, clinical and paraclinical variables, the therapeutic plan and prescription quality were studied. Data was analyzed using descriptive statistics. Results: 57 % (189) patients using glyburide. In 59.3% (153) inappropriately prescribed glibenclamide. 45.5% (86) of the patients had a contraindication to the use of the drug. In 1% of patients were prescribed the sample exceeding the therapeutic dose range Conclusions: The quality of prescribing glyburide was inadequate in a substantial proportion of patients, it is necessary to implement educational strategies that enable medical personnel to ensure proper use of antidiabetic drugs. Glyburide compared with other second-generation sulfonylureas gives us more disadvantages than advantages.

Desenvolvimento de métodos analíticos rápidos e de baixo custo para o controle de qualidade de medicamentos antidiabéticos utilizados no Brasil pelo Sistema Único de Saúde / Development of rapid and low cost analytical methods for the quality control of antidiabetic medications used in Brazil in the Unified Health System

O Diabetes Mellitus (DM) configura-se como uma epidemia mundial, traduzindo-se em um grave desafio para o sistema de saúde pública. Uma das medidas para a manutenção do nível glicêmico normal e redução da morbimortalidade decorrentes do DM consiste no uso de medicamentos antidiabéticos, como a glibenclamida (GLB) e a gliclazida (GLZ). Este trabalho objetivou o desenvolvimento de métodos analíticos inéditos, simples, rápidos, confiáveis e de baixo custo para a determinação espectrofotométrica do teor de GLB e de GLZ em formulações farmacêuticas. Testes qualitativos foram realizados a partir da reação da GLB e da GLZ com a Eosina (EOS). Observou-se a formação de compostos coloridos, opticamente estáveis com absorção máxima em 545 e 543 nm, respectivamente. Sob as condições experimentais otimizadas, curvas analíticas foram obtidas relacionando-se as concentrações de GLB e de GLZ com as absorbâncias equivalentes, contra os brancos de reagentes correspondentes. Os métodos propostos baseiam-se na formação de complexos binários, coloridos e altamente estáveis entre os fármacos investigados e a EOS. Quando aplicados para o doseamento de GLB e de GLZ contidas em amostras comerciais, os resultados obtidos mostraram que não houve diferenças significativas entre os métodos propostos e os métodos oficiais. A realização deste trabalho foi de suma importância, pois permitiu o desenvolvimento de métodos analíticos inéditos, precisos, exatos, confiáveis mais simples, rápidos, versáteis e com maior viabilidade econômica (baixo custo). Estes métodos apresentam potencial para utilização em análises de rotina para o controle de qualidade de fármacos antidiabéticos (GLB e GLZ) presentes em medicamentos consumidos no Brasil.

Diabetes Mellitus (DM) is a global epidemic, which represents a serious challenge for the public health system. One of the measures to maintain the normal glycemic level and reduce morbidity and mortality due to DM is the use of antidiabetic medicines such as glibenclamide (GLB) and gliclazide (GLZ). This work aimed at the development of unpublished, simple, fast, reliable and low cost analytical methods for the spectrophotometric determination of GLB and GLZ content in pharmaceutical formulations. Qualitative tests were performed from GLB and GLZ with Eosin (EOS). The formation of optically stable colored compounds with maximum absorption at 545 and 543 nm, respectively, was observed. Under optimized experimental conditions, analytical curves were obtained by relating the GLB and GLZ concentrations to the equivalent absorbances against the corresponding reagent blank. The proposed methods are based on the formation of binary, colored and highly stable complexes between investigated drugs and EOS. When applied to the GLB and GLZ assay contained in commercial samples, the results showed that there were no significant differences between the proposed methods and the official methods. The accomplishment of this work was of paramount importance, since it allowed the development of unpublished, precise, accurate, reliable, simpler, faster, more versatile analytical methods with greater economic feasibility (low cost). These methods can be used in routine analyzes for the quality control of antidiabetic drugs (GLB and GLZ) present in medicines consumed in Brazil.

Serum concentrations and renal expressions of IL-1 and TNF-a early after hemorrhage in rats under the effect of glibenclamide

ABSTRACT PURPOSE: To investigate changes in the serum concentration and renal expression of IL-1 and TNF-α cytokines in rats that received sevoflurane and glibenclamide prior to hemorrhage. METHODS: Two groups of sevoflurane-anesthetized Wistar rats (n=10): G1 (control) and G2 (glibenclamide, 1 µg/g i.v.); hemorrhage of 30% blood volume (10% every 10 min), with replacement using Ringer solution, 5 ml/kg/h. Serum concentrations of IL-1 and TNF-α were studied in the first hemorrhage (T1) and 50 min later (T2), renal expression, at T2. RESULTS: In serum, G1 TNF-α (pg/mL) was T1=178.6±33.5, T2=509.2±118.8 (p<0.05); IL-1 (pg/mL) was T1=148.8±31.3, T2=322.6±115.4 (p<0.05); in G2, TNF-α was T1=486.2±83.6, T2=261.8±79.5 (p<0.05); IL-1 was T1=347.0±72.0, T2= 327.3±90.9 (p>0.05). The expression of TNF-α and IL-1 in the glomerular and tubular cells was significantly higher in the G2 group. CONCLUSIONS: Hemorrhage and glibenclamide elevated TNF-α and IL-1 concentrations in serum and kidneys. High levels of TNF-α already present before the hemorrhage in the glibenclamide group may have attenuated the damages found in the kidneys after the ischemia event.

Seguridad y eficacia de vildagliptina en el tratamiento de pacientes adultos mayores con diagnóstico de diabetes mellitus tipo 2, con riesgo de hipoglicemia y limitantes para uso de insulina (con alto grado de dependencia), sin control metabólico adecuado (según HBA1C) a pesar de tratamiento con metformina a dosis máxima y glibenclamida / Safety and efficacy of vildagliptin in the treatment of elderly patients with a diagnosis of type 2 diabetes mellitus, with risk of hypoglycemia and limitations of insulin use (with a high degree of dependence), without adequate metabolic control

INTRODUCCIÓN: Antecedentes: El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) ha recibido la solicitud de evaluar el uso de vildagliptina para su uso en pacientes adultos mayores con diagnóstico de diabetes mellitus tipo 2, con riesgo de hipoglicemia y limitantes para uso de insulina (con alto grado de dependencia), sin control metabólico adecuado (según HBA1c) a pesar de tratamiento con metformina a dosis máxima y Glibenclamida dentro del sistema de EsSalud, indicación actualmente no contemplada en el petitorio de medicamentos. Generalidades: La diabetes mellitus tipo 2 (DM-2), forma que representa el 90-95% de los casos de diabetes. Es una enfermedad metabólica crónica que se caracteriza por la pérdida paulatina de la capacidad de secretar insulina a nivel de las células beta del páncreas así como por el aumento progresivo de la resistencia a la insulina, lo cual hace que los pacientes mantengan y eventualmente sufran las consecuencias de mantener niveles elevados de glucosa en su sangre. Como tal la DM-2 constituye una seria amenaza para la salud pública tanto a nivel mundial como en el Perú donde se prevé que pronto se convertirá uno de los principales contribuyentes a la carga de enfermedad en el país. Su incidencia en el Perú se encuentra en aumento. Tecnología Sanitaria de Interés: Los Inhibidores de DPP-4: Los inhibidores de DPP-4 son hipoglicemiantes orales que actúan como inhibidores reversibles de las enzima DPP-4 (dipeptidil peptidasa 4, EC 3.4.14.5), una enzima que está implicada en la inactivación de las hormonas incretinas GLP-1 (péptido similar al glucagón 1) y GIP (polipéptido insulinotrópico dependiente de la glucosa), ambas a su vez implicadas en la regulación fisiológica de la homeostasis de la glucosa. Descubiertos hace ya más de una década, a la fecha en el mercado internacional se disponen de más de ocho diferentes inhibidores de DPP-4. METODOLOGÍA: Estrategia de Búsqueda: El protocolo de esta revisión sistemática fue preparado y revisado con el equipo técnico de IETSI. Las siguientes fuentes han sido revisadas y consultadas: Medline/Pubmed, Embase, Scopus, Web of Science, Trip Database, The Cochrane Library, The National Institute for Health and Care Excellence (NICE) del Reino Unido, The National Guideline Clearinghouse (NCG) de los Estados Unidos, The International Diabetes Federation (IFD). RESULTADOS: uego de revisar un total de 837 documentos resultados de nuestra búsqueda bibliográfica, logramos filtrar 61 estudios relevantes para nuestra pregunta PICO de interés (Tabla 1), de los cuales sólo 8 fueron finalmente seleccionados para nuestro análisis toda vez que constituían estudios relevantes que resumían la mejor evidencia disponible (5 ensayos clínicos, 1 meta-análisis y una guía clínica) sobre la eficacia y seguridad atribuible al uso de un inhibidor de DPP-4 en regímenes de terapia doble (combinado con metformina) o triple (combinado con metformina y una sulfonilurea) comparados con metformina más una sulfonilurea en el manejo de pacientes con diagnóstico de diabetes mellitus de tipo 2. CONCLUSIONES: A la fecha no se puede recomendar el uso de inhibidores de DPP-4 como una alternativa tan o más eficaz y segura a la terapia combinada con metformina y una sulfonilurea, ya sea en regímenes de terapia doble (como reemplazo de la sulfonilurea) o triple (como un tercer hipoglicemiante oral adicional a este esquema de tratamiento) en el manejo de pacientes con diabetes mellitus tipo 2 con mal control metabólico no tributarios de manejo con insulina. La evidencia disponible sugiere que el uso de inhibidores de DDP-4 en un régimen doble (metformina más un inhibidor de DPP-4) si bien es una alternativa de tratamiento que se asocia con un riesgo igual o menor de eventos adversos que la terapia combinada con metformina y una sulfonilurea, no ofrece mayor beneficio en términos de eficacia; mientras que por el contrario, en el caso de la terapia triple (metformina más una sulfonilurea y un inhibidor de DPP-4) si bien sí constituye una alternativa de tratamiento más eficaz que la terapia combinada con metformina y una sulfonilurea se asocia con un mayor riesgo de eventos adversos asociados al tratamiento, y en particular con un mayor riesgo de eventos hipoglicémicos. Asimismo a la fecha, poco se sabe con respecto la seguridad del uso de inhibidores de DPP-4 al largo plazo, en cualquier régimen de tratamiento, desconociéndose en particular cuál puede ser impacto en el riesgo cardiovascular de los pacientes al largo plazo. En consecuencia, no podemos recomendar el uso de ningún inhibidor de DPP-4 en regímenes de terapia dual o triple, en el tratamiento de pacientes adulto mayores de 60 años con diagnóstico de DM-2, con riesgo de hipoglicemia y limitantes para uso de insulina (con alto grado de dependencia*), sin control metabólico adecuado (según HbAl c) con metformina a dosis máxima y Glibenclamida por cuanto no se disponen de evidencias suficientes para sobrepesar los beneficios con respecto a los riesgos al largo plazo que su uso pueda tener.

Pharmacological study of the mechanisms involved in the vasodilator effect produced by the acute application of triiodothyronine to rat aortic rings

A relationship between thyroid hormones and the cardiovascular system has been well established in the literature. The present in vitro study aimed to investigate the mechanisms involved in the vasodilator effect produced by the acute application of 10-8–10-4 M triiodothyronine (T3) to isolated rat aortic rings. Thoracic aortic rings from 80 adult male Wistar rats were isolated and mounted in tissue chambers filled with Krebs-Henseleit bicarbonate buffer in order to analyze the influence of endothelial tissue, inhibitors and blockers on the vascular effect produced by T3. T3 induced a vasorelaxant response in phenylephrine-precontracted rat aortic rings at higher concentrations (10-4.5–10-4.0 M). This outcome was unaffected by 3.1×10-7 M glibenclamide, 10-3 M 4-aminopyridine (4-AP), 10-5 M indomethacin, or 10-5 M cycloheximide. Contrarily, vasorelaxant responses to T3 were significantly (P<0.05) attenuated by endothelium removal or the application of 10-6 M atropine, 10-5 M L-NG-nitroarginine methyl ester (L-NAME), 10-7 M 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 10-6 M (9S,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i](1,6)benzodiazocine-10-carboxylic acid, methyl ester KT 5823, 10-2 M tetraethylammonium (TEA), or 10-7 M apamin plus 10-7 M charybdotoxin. The results suggest the involvement of endothelial mechanisms in the vasodilator effect produced by the acute in vitro application of T3 to rat aortic rings. Possible mechanisms include the stimulation of muscarinic receptors, activation of the NO-cGMP-PKG pathway, and opening of Ca2+-activated K+ channels.

Permanent neonatal diabetes by a new mutation in KCNJ11: unsuccessful switch to sulfonylurea

Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (KATP). Sulfonylureas promote KATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene – KCNJ11:c1001G>7 (p.Gly334Val) – and confirmed the diagnosis of PNDM. Therefore it was attempted to switch from insulin therapy to sulfonylurea. During glibenclamide institution C-peptide levels increased, however the suboptimal glycemic control lead us to restart an intensive insulin scheme. This new variant of KCNJ11 mutation had a phenotypic lack of response to sulfonylurea therapy. Age, prior poor metabolic control and functional change of KATP channel induced by this specific mutation may explain the observed unsuccessful switch to sulfonylurea. Interestingly, C-peptide levels raise during glibenclamide administration support some degree of improvement in insulin secretory capacity induced by the treatment. Understanding the response to sulfonylurea is crucial as successful treatment may be life-changing in these patients.

Metformina y gliburida en el tratamiento de la diabetes gestacional / Metformin and glyburide in the treatment of gestational diabetes

INTRODUCCIÓN: La diabetes gestacional es una alteración de la tolerancia a la glucosa de severidad variable reconocida por primera vez en el embarazo en curso. La insulina ha sido el tratamiento farmacológico estándar para la diabetes gestacional, sin embargo la metformina y la gliburida son alternativas terapéuticas para el control de la glicemia. OBJETIVO: Determinar las ventajas de la metformina y la gliburida sobre la insulina en el tratamiento de la diabetes gestacional. MATERIALES Y MÉTODOS: Se realizó una búsqueda sistemática en las bases de datos Medline (PubMed) y Scielo. Los términos DeCS utilizados fueron: "Diabetes Gestacional", "Gliburida", y "Metformina" en diferentes combinaciones; sus homólogos MeSH fueron: "Diabetes, Gestational", "Glyburide" y "Metformin". La búsqueda obtenida incluyó 130 artículos, de los cuáles fueron seleccionados 53. RESULTADOS: La gliburida es un medicamento categoría C en el embarazo. Sus concentraciones en cordón umbilical son insignificantes y es considerado seguro. Su tasa de éxito para lograr el control de la glicemia c varía del 79% al 86%. La metformina es un medicamento categoría B en el embarazo. No ha mostrado efectos teratógenos en el primer trimestre del embarazo y logra un control de la glicemia en 24 horas. CONCLUSIONES: La metformina y la gliburida logran valores de control de glicemia en diabetes gestacional similares a la insulina y no aumentan la teratogénesis en el primer trimestre del embarazo. Las complicaciones perinatales por su uso deben ser más estudiadas

INTRODUCTION: Gestational diabetes is an impaired glucose tolerance of variable severity first recognized in the current pregnancy. Insulin has been the standard drug treatment for gestational diabetes, however metformin and glyburide are therapeutic alternatives to control glycemia. OBJECTIVE: Determine the advantages of metformin and glyburide over insulin in the treatment of gestational diabetes. MATERIALS AND METHODS: A systematic research was performed in the databases Medline (PubMed) and Scielo. The DeCS terms used were: "Diabetes Gestacional", "Gliburida", and "Metformina" in different combinations; MeSH counterparts were: "Diabetes, Gestational", "Glyburide" and "Metformin". The search obtained covered 130 articles, of which 53 were selected. RESULTS: Glyburide is a category C drug in pregnancy. Their concentrations in umbilical cord are insignificant and is considered safe. Its success rate to achieve glycemic control ranges from 79% to 86%. Metformin is a category B drug in pregnancy. It has shown no teratogenic effects in the first trimester of pregnancy. It achieves glycemic control in 24 hours. CONCLUSIONS: Metformin and glyburide achieved glycemic control values in gestational diabetes similar to insulin. They do not increase the teratogenesis in the first trimester of pregnancy. Perinatal complications from its use should be more studied

Uso de hipoglicemiantes orais em pacientes com Diabetes Mellitus gestacional / Oral hypoglycemic in patients with gestational Diabetes Mellitus

O Diabetes Mellitus Gestacional (DMG) é definido como intolerância a carboidratos com início ou diagnóstico durante a gestação. Em gestantes com DMG, é importante o controle da glicemia a fim de reduzir ou evitar efeitos adversos como abortamento, malformações congênitas e crescimento fetal anormal. Tradicionalmente, a insulina é usada como medicamento de escolha, segura para mãe e feto e eficaz no sentido de controlar os valores glicêmicos maternos. A Metformina é um hipoglicemiante oral que age aumentando a sensibilidade dos tecidos à insulinaNos estudos disponíveis, quando comparada à insulina, a Metformina mostra uma menor taxa de hipoglicemia neonatal grave, porém, não foi observada diferença significativa em relação a outros resultados perinatais, tal como prematuridade. A gliburida é um hipoglicemiante que aumenta a secreção de insulina pelas células beta pancreáticas. É uma droga bem tolerada e apresenta baixa taxa de hipoglicemia materna, em torno de 1,5% das pacientes. A gliburida mostrou eficácia semelhante à insulina em diversos estudos no controle glicemico. Mais estudos clínicos randomizados se fazem necessários no momento atual de discussão sobre os reais benefícios e riscos dessas drogas, a fim de definir seu papel efetivo no tratamento do DMG, consolidando ou não, sua recomendação e seu uso amplo.(AU)

Gestational Diabetes (GMD) is defined as carbohydrate intolerance with onset or first recognition during pregnancy. In pregnants, with GMD the glucose control is important to minimize the risk of miscarriage, fetal congenital malformations and macrossomia. Traditionally, insulin is used, since it does not cross the placenta, being considered safe for the woman and the fetus. Metformin is a hypoglycemic agent that acts as an insulin sensitizer, inhibits gluconeogenesis, suppresses hepatic glucose output and increase intestinal glucose absorption. It crosses the placenta, but it is not considered teratogenic. When compared with insulin, Metformin shows a lower incidence of severe neonatal hypoglycemia, with no difference in rates of other perinatal complications, as prematurity. Glyburide is a hypoglycemic that increases insulin secretion by pancreatic beta cells and sensitivity in peripheral tissues and reducing hepatic clearance of insulin. It shows similar efficacy of insulin on glucose control with a lower rate of maternal hypoglycemia, around 1.5% of patients. The glyburide showed similar efficacy to insulin in several studies in glycemic control. It is still suggested that the use of agent hypoglycemic on DMG can induce a lower maternal weight gain and more treatment adherence. More randomized clinical studies are required to ensure the real benefits and risks of these drugs, in order to define its use on GMD treatment.(AU)

Uso de hipoglicemiantes orales durante la lactancia / Use of oral hypoglycemic agents during breastfeeding

Antecedentes: Los hipoglicemiantes orales son una alternativa emergente en el tratamiento de la diabetes mellitus gestacional (DMG), pero existe poca información acerca de su uso durante la lactancia. Objetivo: Revisar la evidencia respecto a la seguridad del uso de los hipoglicemiantes orales durante la lactancia. Resultados: Encontramos 3 trabajos que evaluaron el paso de metformina a la leche materna: hubo traspaso de metformina a leche materna en todos los casos. La concentración de metformina excretada a la leche fue en promedio 48 por ciento de la concentración plasmática materna. Las dosis calculadas que recibieron los lactantes en promedio fue 0,38 por ciento de la dosis materna, ajustada por peso. La concentración promedio de metformina en los lactantes fue de 0,025 mg/L. No se reportaron efectos adversos en los lactantes, incluso en el seguimiento a 6 meses de vida. Se encontró sólo un trabajo en relación a glibenclamida y lactancia materna, en el que no se detectó excreción del fármaco a la leche materna. Conclusiones: Los hipoglicemiantes orales parecen ser medicamentos seguros durante la lactancia, sin embargo, la evidencia es escasa. Sugerimos el uso de la glibenclamida por sobre metformina, por su nulo paso a la leche materna.

Background: Oral hypoglycemic agents are an emergent therapy for the treatment of gestational diabetes mellitus (GDM), but there is little information about its use during breastfeeding. Objectives: To review the available evidence regarding the use and safety of oral hypoglycemic agents during breastfeeding. Results: We found 3 studies that described the transfer of metformin to breast milk; there was transfer of metformin to breast milk in all cases. The concentration of metformin in breast milk was 48 percent of the maternal plasma concentration. The calculated dose for the infants was 0.38 percent of the maternal weight adjusted dose. The mean concentration of metformin in the infant's plasma was 0.025 mg/L. No adverse effects were reported in the infants, including 6 months of follow-up. Only one study investigated glyburide and breastfeeding, showing no excretion to breast milk. Conclusion: Oral hypoglycemic agents seem to be safe during breastfeeding; however, the available data is scarce. We suggest the use of glyburide over metformin because of its null excretion to breast milk.

Medicamentos de ação metabólica: Estatinas, fibratos e antidiabéticos orais / Drugs of metabolic action: Statins, fibrates and oral antidiabetics

A polifarmácia na prática clínica atualmente é necessária paraa obtenção de metas de tratamento mais rigorosas impostas porestudos que vêm demonstrando seus benefícios. O pacienteque apresenta alterações metabólicas está mais suscetível aouso de medicamentos hipolipemiantes e antidiabéticos orais.A interação medicamentosa entre esses e outros fármacosfaz com que devamos nos atentar aos mecanismos de ação,metabolização e excreção dessas drogas...

Multiple drugs used in clinical practice are required to obtain morestrict treatment goals determined by studies that have demonstratedtheir benefits. Metabolic alterations in patients are more likelyto be treated with lipid lowering drugs and oral antidiabetics.We should pay close attention to their rnechanisms of action,metabolism and excretion, due to their interaction with otherdrugs...