Gianni Mara Silva dos Santos

Intrauterine Growth Restriction Programs the Hypothalamus of Adult Male Rats: Integrated Analysis of Proteomic and Metabolomic Data

Programming of hypothalamic functions regulating energy homeostasis may play a role in intrauterine growth restriction (IUGR)-induced adulthood obesity. The present study investigated the effects of IUGR on the hypothalamus proteome and metabolome of adult rats submitted to 50% protein-energy restriction throughout pregnancy. Proteomic and metabolomic analyzes were performed by data independent acquisition mass spectrometry and multiple reaction monitoring, respectively. At age 4 months, the restricted rats showed elevated adiposity, increased leptin and signs of insulin resistance. 1356 proteins were identified and 348 quantified while 127 metabolites were quantified. The restricted hypothalamus showed down-regulation of 36 proteins and 5 metabolites and up-regulation of 21 proteins and 9 metabolites. Integrated pathway analysis of the proteomics and metabolomics data indicated impairment of hypothalamic glucose metabolism, increased flux through the hexosamine pathway, deregulation of TCA cycle and the respiratory chain, and alterations in glutathione metabolism. The data suggest IUGR modulation of energy metabolism and redox homeostasis in the hypothalamus of male adult rats. The present results indicated deleterious consequences of IUGR on hypothalamic pathways involved in pivotal physiological functions. These results provide guidance for future mechanistic studies assessing the role of intrauterine malnutrition in the development of metabolic diseases later in life.

Desenvolvimento e pré-teste de um questionário de frequência alimentar para graduandos

Objetivo Desenvolver e aplicar em um projeto-piloto um questionario de frequencia alimentar quantitativo de autopreenchimento destinado a graduandos da area da saude. Metodos Trata-se de um estudo transversal realizado em 151 universitarios de ambos os sexos, usuarios do ambulatorio de Nutricao do Corpo Discente da Universidade Federal de Sao Paulo, Brasil. O questionario inicial foi composto a partir dos alimentos e preparacoes informados no Registro Alimentar de Tres Dias. As informacoes em medidas caseiras foram transformadas em gramas ou mililitros com o auxilio de tabelas, e os alimentos foram ordenados segundo a porcentagem de contribuicao para o valor energetico total informado. Foram selecionados 198 ali-mentos responsaveis por 95% do consumo energetico e agrupados em 77 itens alimentares de acordo com a similaridade nutricional. O tamanho das porcoes alimentares foi classificado conforme o valor do percentil 50 da distribuicao dos pesos correspondentes as medidas caseiras referidas. Definiu-se como porcao pequena, aquela cujo valor foi igual ou inferior ao percentil 25; como media, o percentil 50 e grande, o valor igual ou superior ao percentil 75. Resultados Apos o pre-teste do questionario inicial, o questionario final resultou em uma lista com 89 alimentos, agrupados em 70 itens alimentares. As instrucoes para o autopreenchimento foram refeitas, objetivando-se um melhor preenchimento. Conclusao Apos as modificacoes realizadas, o questionario de frequencia alimentar quantitativo encontra-se pronto para o estudo de validacao e calibracao.

Obstructive sleep apnea prevents the expected difference in craniofacial growth of boys and girls

OBJECTIVES It was to compare cephalometric measures of mouth-breather boys and girls and with the cephalometric pattern observed in obstructive sleep apnea syndrome (OSAS) patients. METHODS Craniofacial measurements of lateral cephalometric radiographs obtained from 144 children aged 7-14 years were compared between boys and girls, and both were compared to cephalometric pattern of OSAS patients. RESULTS Mouth-breather boys and girls had no gender differences regarding to craniofacial morphology while nose-breather boys and girls showed those expected differences. Nose-breather boys presented a more retruded mandible and proinclined upper incisor when compared to nose-breather girls, but mouth-breather boys and girls had no differences. The measure NS.GoGn was the only variable with an interaction with gender and breathing. CONCLUSIONS There were no cephalometric difference in mouth breather-boys and girls related to normal growth, suggesting that oral breathing make the same craniofacial morphology and both have craniofacial morphology close to that of OSAS patients.

Remarks about systematic reviews of diagnostic tests.

century, the evolution of medicine was seen to be accelerating, and the new millennium began with a fast pace. Doctors and other health pro-fessionals cannot survive unless they are up to date with the constant changes imposed by tech -nology, especially in big cities.Over the last few decades, the avalanche of new drugs and modern methods of treatment has encouraged doctors to look for faster ways to follow these changes, as well as ways to verify the true efficacy of these new interventions. All of these changes led to evidence-based medi-cine, which has subsequently become known as evidence-based healthcare, when other health-care professionals are included in this.Evidence consists of nothing more than the results of assessments through scientific studies with reproducible methodological quality (for all the data described in the work). This is pos-sible in intervention studies on high-prevalence diseases because they present large numbers of participants. However, in cases of low-prevalence diseases, the results give rise to doubts. This has led to the use of systematic reviews, since these are able to fulfill the need to evaluate inter-vention studies. However, this is only possible when studies are designed to have similar objec-tives and interventions and their methodological quality can be assessed. In a systematic review, it is desirable and often feasible to obtain the sum of statistical data from several studies, which is called meta-analysis.More recently, the same need has arisen in the field of diagnostics. The evolution of diagnos -tic equipment and the emergence of new laboratory kits with promises of faster, more accurate and less invasive diagnostic methods has been widely broadcasted in the media. This directly influences patients’ opinions, and affects the people responsible for doing the examinations and governments. Patients obviously want to have access to the best examination that there is, while professionals and governments want to make sure that these new tests really are superior to the existing ones, so that the possibly high financial investment can be justified. Therefore, system-atic reviews on diagnostic accuracy studies are considered to be of great relevance.Given the lack of consensus on the most appropriate way of conducting the systematic review method, the Cochrane Collaboration, a pioneer in implementing systematic reviews on intervention studies, decided to disseminate and encourage the development of systematic reviews on accuracy studies by creating a section aimed only at reviews on diagnostic accu-racy studies. This new section forms part of the RevMan (Review Manager) software, which the Cochrane Collaboration maintains in order to guide the elaboration of reviews and enable pro -duction of meta-analysis whenever possible. This brilliant initiative has caught the attention of many researchers and has encouraged them to work in this field, but just as in any other move-ment in its initial phase, several unresolved issues still hinder the work.The tools for assessing the quality of individual diagnostic accuracy studies are different from those applied in intervention studies. This has generated great confusion among research -ers and among editorial boards evaluating such studies. There are several published system-atic reviews on accuracy studies that are full of inappropriate terms and were methodologically designed as if they were intervention studies. Furthermore, there is a lack of significant accuracy values, such as sensitivity, specificity and predictive values.

L-arginine abolishes the hypothalamic serotonergic activation induced by central interleukin-1β administration to normal rats

IL-1β-induced anorexia may depend on interactions of the cytokine with neuropeptides and neurotransmitters of the central nervous system control of energy balance and serotonin is likely to be one catabolic mediator targeted by IL-1β. In the complex interplay involved in feeding modulation, nitric oxide has been ascribed a stimulatory action, which could be of significance in counteracting IL-1β effects.The present study aims to explore the participation of the nitric oxide and the serotonin systems on the central mechanisms induced by IL-1β and the relevance of their putative interactions to IL-1β hypophagia in normal rats.Serotonin levels were determined in microdialysates of the ventromedial hypothalamus after a single intracerebroventricular injection of 10 ng of IL-1β , with or without the pre-injection of 20 μg of the nitric oxide precursor L-arginine. IL-1β significantly stimulated hypothalamic serotonin extracellular levels, with a peak variation of 130 ±37% above baseline. IL- 1β also reduced the 4-h and the 24-h food intakes (by 23% and 58%, respectively). The IL-1β-induced serotonergic activation was abolished by the pre-injection of L-arginine while the hypophagic effect was unaffected.The data showed that one central effect of IL-1β is serotonergic stimulation in the ventromedial hypothalamus, an action inhibited by nitric oxide activity. It is suggested that, although serotonin participates in IL-1β anorexia, other mechanisms recruited by IL-1β in normal rats are able to override the absence of the serotonergic hypophagic influence.