Undernutrition - thirty years of the Regional Basic Diet: the legacy of Naíde Teodósio in different fields of knowledge.

Undernutrition is characterized by an imbalance of essential nutrients with an insufficient nutritional intake, a disorder in which the clinical manifestations in most cases are the result of the economic and social context in which the individual lives. In 1990, the study by the medical and humanitarian Naíde Teodósio (1915-2005) and coworkers, which formulated the Regional Basic Diet (RBD) model for inducing undernutrition, was published. This diet model took its origin from the observation of the dietary habits of families that inhabited impoverished areas from the Pernambuco State. RBD mimics an undernutrition framework that extends not only to the Brazilian population, but to populations in different regions worldwide. The studies based on RBD-induced deficiencies provide a better understanding of the impact of undernutrition on the pathophysiological mechanisms underlying the most diverse prevalent diseases. Indexed papers that are analyzed in this review focus on the importance of using RBD in different areas of knowledge. These papers reflect a new paradigm in translational medicine: they show how the study of pathology using the RBD model in animals over the past 30 years has and still can help scientists today, shedding light on the mechanisms of prevalent diseases that affect impoverished populations.

Histone Deacetylase Activity and the Renin-Angiotensin-Aldosterone System: Key Elements in Cardiorenal Alterations Provoked by Chronic Malnutrition in Male Adult Rats.

BACKGROUND/AIMS: Chronic malnutrition (M) affects >1 billion people worldwide. Epidemiological data point to long-term renal and cardiovascular outcomes (e.g. arterial hypertension, cardiorenal syndromes). The renin-angiotensin-aldosterone system (RAAS) has been implicated in the physiopathology of these disturbances, but M-induced alterations in RAAS-modulated renal Na+ handling and their cardiovascular repercussions are not known. Moreover, altered tissue-specific histone deacetylases (HDAC) results in arterial hypertension and the use of sodium Valproate (Val; a HDAC inhibitor) reduces blood pressure. However, there are no reports regarding the renal and cardiovascular effects of HDAC inhibition in M, or on the signaling pathways involved. The central aim of our study has been to investigate whether alterations in the HDAC/RAAS axis underpin alterations in active Na+ transport in the kidney and heart, and affects blood pressure. METHODS: Male rats aged 28 days were given either a control (C) or a multideficient diet (Regional Basic Diet, RBD), which mimics alimentary habits from developing countries. Subgroups received Losartan (Los), a blocker of type 1 Angiotensin II receptors. When the rats reached 70 days, new subgroups received Val until they were 90 days of age. Homogenates and enriched plasma membrane fractions from renal cortex corticis and cardiomyocytes were obtained by differential centrifugation of the tissues. The activity of renal and cardiac deacetylases was assayed by measuring - after incubation with the membranes - the amount of deacetylated lysines in a substrate containing an acetylated lysine side chain. Protein kinases activities were measured following the incorporation of the γ-phosphoryl group of [γ-32P]ATP into Ser/Thr residues of histone type III-S. The activity of Na+-transporting ATPases (kidney and heart) was quantified by measuring the release of Pi from ATP that was sensitive to ouabain ((Na++K+)ATPase), or sensitive to furosemide (Na+-ATPase). Tail-cuff plethysmography was used to measure systolic blood pressure and heart rate. RESULTS: M provoked HDAC downregulation, which was reversed by Los and Val, either alone or in combination, with selective upregulation of protein kinases C and A (PKC, PKA) in renal cortex corticis, but not in left ventricle cardiomyocytes. The 2 kinases were strongly inhibited by Los and Val in both organs. Malnourished rats developed elevated systolic arterial pressure (SAP) and heart rate (HR) at 70 days of age; Los and Val restored the control SAP, but not HR. Functional and the above biochemical alterations were associated with the deregulation of renal and cardiac Na+-transporting ATPases. (Na++K+)ATPase activities were downregulated in M rats in both organs, and were further inhibited by the pharmacological treatments in the renal cortex corticis (C and M groups) and the left ventricle (only in C rats). No additional effect was found in cardiac (Na++K+)ATPase from M rats. Ouabain-resistant Na+-ATPase was upregulated in renal cortex corticis and downregulated in cardiomyocytes, returning to C values after administration of Los and Val. CONCLUSION: The HDAC/RAAS axis appears to be a key regulator of Na+-transporting ATPases in renal cortex corticis and cardiomyocytes via an appropriate balance of PKC and PKA activities. Modifications within the HDAC/RAAS axis provoked by chronic M - with repercussions in renal and cardiac Na+ transport - underpin alterations in bodily Na+ homeostasis that culminate with the onset of arterial hypertension and potential cardiorenal syndrome.

Parâmetros a serem considerados no tratamento e controle do Diabetes Gestacional / Parameters to be considered in the treatment and control of Gestational Diabetes

O diabetes gestacional é uma doença metabólica crônica, cuja principal característica é a resistência insulínica, que repercute na morbidade materna e nos desfechos perinatais. Sua prevalência no Brasil está em torno de 7 a 10%. Quando utilizados valores glicêmicos mais baixos do que aqueles anteriormente propostos, um grupo maior de gestantes é enquadrado no diagnóstico desta doença, contribuindo para aumento de sua incidência. Diante deste fato e dos diversos efeitos adversos do diabetes, como hiperinsulinemia fetal e macrossomia, é necessário instituir uma terapêutica rápida e eficaz. A decisão em iniciar esta terapêutica baseia-se em conceitos sabidamente conhecidos, tais como valores glicêmicos de controle, estudo ecográfico fetal (medida da circunferência abdominal), idade gestacional e obesidade materna. Neste trabalho, esses conceitos foram discutidos após uma revisão dos artigos atuais e de maior relevância cientifica.(AU)

The gestational diabetes is a metabolic chronic disorder which main feature is the insulin resistance and its consequences as maternal morbidity and perinatal outcomes. The prevalence in Brazil is from 7 to 10%. When we use lower targets of glycemic control than those previously used, a greater group of pregnants fits into the diagnosis of diabetes, and thereby increasing the incidence of the disease. Towards this and the several adverse outcomes, as fetal hyperinsulinemia and macrossomia, an early and effective treatment has to be established. The decision in begin the therapy is based on elements already known, as the glycemic targets, fetal ultrasound (abdominal circumference measure), gestational age and maternal obesity. These elements are discussed in this paper after a literature review of the latest and more scientific important articles.(AU)