Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance.

OBJECTIVE: Oxidative stress and mitochondrial dysfunction are implicated in polycystic ovary syndrome (PCOS). The present study assesses the effect of metformin treatment on mitochondrial function in polymorphonuclear cells from PCOS subjects. Additionally, we evaluate endocrine parameters and levels of interleukin 6 (IL6) and tumour necrosis factor alpha (TNFα). DESIGN AND METHODS: Our study population was comprised of 35 women of reproductive age diagnosed with PCOS and treated with metformin for 12 weeks, and their corresponding controls (n=41), adjusted by age and BMI. We evaluated the alteration of endocrinological and anthropometrical parameters and androgen levels. Mitochondrial O2 consumption (using a Clark-type O2 electrode), membrane potential, mitochondrial mass, and levels of reactive oxygen species (ROS) and glutathione (GSH) (by means of fluorescence microscopy) were assessed in poymorphonuclear cells. H2O2 was evaluated with the Amplex Red(R) H2O2/Peroxidase Assay kit. IL6 and TNFα were measured using the Luminex 200 flow analyser system. RESULTS: Metformin had beneficial effects on patients by increasing mitochondrial O2 consumption, membrane potential, mitochondrial mass and glutathione levels, and by decreasing levels of reactive oxygen species and H2O2. In addition, metformin reduced glucose, follicle-stimulating hormone, IL6 and TNFα levels and increased dehydroepiandrosterone sulfate levels. HOMA-IR and mitochondrial function biomarkers positively correlated with ROS production (r=0.486, P=0.025), GSH content (r=0.710, P=0.049) and H2O2 (r=0.837, P=0.010), and negatively correlated with membrane potential (r=-0.829, P=0.011) at baseline. These differences disappeared after metformin treatment. CONCLUSIONS: Our results demonstrate the beneficial effects of metformin treatment on mitochondrial function in leukocytes of PCOS patients.

Altered mitochondrial function and oxidative stress in leukocytes of anorexia nervosa patients.

CONTEXT: Anorexia nervosa is a common illness among adolescents and is characterised by oxidative stress. OBJECTIVE: The effects of anorexia on mitochondrial function and redox state in leukocytes from anorexic subjects were evaluated. DESIGN AND SETTING: A multi-centre, cross-sectional case-control study was performed. PATIENTS: Our study population consisted of 20 anorexic patients and 20 age-matched controls, all of which were Caucasian women. MAIN OUTCOME MEASURES: Anthropometric and metabolic parameters were evaluated in the study population. To assess whether anorexia nervosa affects mitochondrial function and redox state in leukocytes of anorexic patients, we measured mitochondrial oxygen consumption, membrane potential, reactive oxygen species production, glutathione levels, mitochondrial mass, and complex I and III activity in polymorphonuclear cells. RESULTS: Mitochondrial function was impaired in the leukocytes of the anorexic patients. This was evident in a decrease in mitochondrial O2 consumption (P<0.05), mitochondrial membrane potential (P<0.01) and GSH levels (P<0.05), and an increase in ROS production (P<0.05) with respect to control subjects. Furthermore, a reduction of mitochondrial mass was detected in leukocytes of the anorexic patients (P<0.05), while the activity of mitochondrial complex I (P<0.001), but not that of complex III, was found to be inhibited in the same population. CONCLUSIONS: Oxidative stress is produced in the leukocytes of anorexic patients and is closely related to mitochondrial dysfunction. Our results lead us to propose that the oxidative stress that occurs in anorexia takes place at mitochondrial complex I. Future research concerning mitochondrial dysfunction and oxidative stress should aim to determine the physiological mechanism involved in this effect and the physiological impact of anorexia.

Mitochondria-targeted antioxidants as a therapeutic strategy for protecting endothelium in cardiovascular diseases.

Endothelial dysfunction involving dysfunctional mitochondria precedes the development of cardiovascular diseases. This impairment results from an increase in reactive oxygen species, which leads to oxidative stress and a reduced bioavailability of nitric oxide. It has been demonstrated that oxidative stress and alterations in glucose and lipid homeostasis (e.g. hyperinsulinemia, hyperglycemia, insulin resistance and dyslipidemia) are linked to mitochondrial impairment and that all of them contribute to endothelial dysfunction. Anti-hyperlipidemic drugs such as statins, anti-hypertensive drugs and angiotensin receptor antagonists have been shown to exert protection through anti-oxidative stress mechanisms. Other substances with antioxidant properties, such as vitamins, are also capable of abolishing the oxidative stress associated with cardiometabolic diseases. However, the results obtained with general antioxidants in clinical trials are contradictory, perhaps due to the unspecific nature of the targets selected. This study correlates endothelial dysfunction and mitochondrial dysfunction and examines current research for the selective targeting of specific molecules (such as ·NO donors and antioxidants) to mitochondria with the aim of protecting the endothelium against oxidative stress in cardiovascular diseases.

The pivotal role of nitric oxide: effects on the nervous and immune systems.

Nitric oxide (NO) has an important role in physiological and pathological processes in general, and in particular plays a homeostatic role in the nervous and immune systems. The many different physiological functions of NO include those of a mediator of blood vessel dilation, neurotransmitter, neuromodulator and inductor of mitochondrial biogenesis. In addition, NO can transform into highly reactive and harmful molecules producing an impairment of the DNA, lipids or proteins, and thus altering their function. This dual action of NO, by which it plays an important role in homeostasis and aids the development of pathological processes, makes this molecule an interesting target for medical therapies, especially with respect to the nervous and immune systems. This review describes the multiple roles of NO played out in the nervous and immune systems during different physiological and pathophysiological processes.

Mitochondrial dysfunction and oxidative stress in insulin resistance.

Evidence is mounting of the involvement of mitochondrial dysfunction in insulin resistance, diabetes and associated complications. This review aims to provide an overview of the effects of insulin resistance on mitochondrial function in several tissues. We consider the pathogenesis of insulin resistance from a mitochondrial perspective and contemplate potential beneficial effects of strategies aimed at modulating mitochondrial function in insulin resistance, including insulin and insulin-sensitizing drugs, antioxidants, and selectively targeting antioxidants to mitochondria.

Desempenho clínico das restaurações do tipo inlay/onlay de cerâmica / Clinical longevity of the all-ceramic inlay/onlay restorations

Este estudo procurou revisar e analisar a literatura pertinente dos últimos anos (1996-2002) que determina a longetividade clínica das restaurações do tipo inlay/onlay de cerâmica e as características que influenciam no sucesso dessas restaurações. Podemos observar que essa técnica restauradora possui um bom índice de sucesso nos trabalhos de curta duração, embora o sucesso em longo prazo ainda não esteja bem estabelecido. Conclui-se que essa técnica ocupa um lugar de destaque na odontologia estética atual e que, com o contínuo desenvolvimento dos materiais cerâmicos, torna-se-á uma alternativa estética e funcional na restauração de dentes posteriores

Avaliação das alterações estruturais em esmalte submetido ao clarareamento com peróxido de hidrogênio a 35 / Evaluation of enamel structure changes when submitted to 35 hydrogen peroxide

O objetivo deste estudo foi avaliar e classificar as alterações morfológicas sobre o esmalte de dentes humanos hígidos submetidos ao tratamento clareador com peróxido de hidrogênio a 35% em duas formas comerciais: (Whiteness HP-FGM) e farmácia de manipulação (PhD), com diferentes tempos de ação dos clareadores, através de análise em microscopia eletrônica de varredura (MEV). Este estudo também sugere uma nova metodologia para análise das alterações topográficas decorrentes dessa modalidade de tratamento. O agente clareador PhD apresentou diferença estatisticamente significante (p<0,001) produzindo os maiores valores ordinais quando comparado ao agente clareador FGM. Houve uma correlação positiva estatisticamente significante (p<0,001) entre ambos os agentes

Facetas e prótese fixa Procera: relato de caso clínico / Procera laminate veneers and fixed prosthesis: a clinical case report

Este trabalho tem como objetivo discutir as principais indicações do sistema Procera All Ceram, como também, relatar um caso clínico realizado na clínica de especialização em Dentística Restauradora da Universidade do Estado do Rio de Janeiro (UERJ), onde foram confecionadoas um aponte fixa e duas facetas Procera, que estão sendo acompanhadas pelos autores

A relaçäo entre bruxismo dental e implantes endósseos / Relationship between bruxism and endosseous implants

Vários estudos longitudinais vêm demonstrar a excelente confiabilidade do tratamento com implantes endósseos. As bases para o seu sucesso säo um correto planejamento protético e conhecimento técnico-científico acerca do biomaterial empregado na fabricaçäo do implante. A proposta deste estudo é revisar na literatura os possíveis riscos e problemas de um paciente identificado como bruxoma, no planejamento protocolar pré-implante, onde tensöes geradas da oclusäo constituem um fator predisponente a falhas no tratamento devido aos altos níveis de sobrecarga gerada no implante

Tratamento ortodôntico-restaurador combinado: um recurso nas alteraçöes de forma dentária (relato de caso) / Orthodontic restorative treatment: a tool for tooth morphological alterations (case report)

O restabelecimento de um sorriso harmônico constitui um desafio para a odontologia restauradora frente às alteraçöes de forma e tamanho, que afetam a proporçäo áurea dos dentes. Deste modo, propöe-se, neste trabalho, uma técnica alternativa restauradora estética para a reanatomizaçäo e recontorno estético em "incisivos laterais conóides" e diastemas interincisais, através da utilizaçäo de sistemas adesivos resinosos diretos. Os resultados alcançados foram esteticamente satisfatórios, favorecendo a continuidade do plano de tratamento clínico que se encontra em fase de movimentaçäo ortodôntica fixa

Aspectos atuais do ensino pré-clínico em dentística operatória / Actual aspects of the preclinical training in operative dentistry

O desenvolvimento da Dentística Restauradora dos nossos dias atuais manifesta-se predominantemente em virtude do aparecimento de novos materiais e técnicas restauradoras. Sendo assim, esta condiçäo exige treinamento pré-clínico mais apurado na execuçäo de suas tarefas no laboratório. O objetivo do estudo foi mostrar a viabilidade de aperfeiçoamento dos métodos de aprendizado pré-clínico em Dentística, quando se utilizou dentes naturais extraídos, de modo a preparar o estudante para o trabalho clínico atual

Parasitosis intestinales en guarderías comunitarias de Montevideo / Intestinal parasitosis in community day care centers in Montevideo

Con la finalidad de mejorar las condiciones de salud y bienestar de los preescolares que asisten a guarderías comunitarias del Programa Nuestros Niños de la Intendencia Municipal de Montevideo, se están realizando estudios parasitológicos enmarcados en un convenio entre la misma y la Universidad de la República a través de la Facultad de Medicina (Departamento de Parasitología del Instituto de Higiene) desde 1991. Se informan en la presente comunicación los resultados obtenidos durante 1997 en las 16 guarderías estudiadas. Se trazó un plan que comprendía la realización de actividades informativas y educativas, actividades de diagnóstico mediante exámenes coproparasitarios y espátulas adhesivas, y actividades terapéuticas de acuerdo con los agentes hallados. Con el plan utilizado se logró una disminución de la prevalencia del parasitismo global en el segundo semestre del año para los agentes de transmisión directa. El control de las enteroparasitosis debe formar parte de proyectos interdisciplinarios más ambiciosos que incluyan decisiones sobre saneamiento ambiental y mejora de la vivienda y de las condiciones de vida de los pobladores que habitan el cinturón periférico de dicha ciudad