Marcadores bioquímicos propuestos para el estudio de la sarcopenia / Proposed biochemical markers for the study of sarcopenia

La sarcopenia asociada a la edad es una condición clínica caracterizada por una disminución en la fuerza, calidad y cantidad de masa muscular así como también en la función muscular. Un biomarcador se define como una característica que es medible objetivamente y evaluable como indicador de un proceso biológico normal, patológico o respuesta terapéutica a una intervención farmacológica. Los marcadores bioquímicos propuestos para el estudio de la sarcopenia pueden ser categorizados en dos grupos. El primero de ellos evalúa el estatus musculoesquelético; este panel de marcadores está formado por miostatina/folistatina, procolágeno aminoterminal tipo III e índice de sarcopenia. El segundo grupo de marcadores bioquímicos evalúa factores causales, para lo cual se sugiere medir el factor de crecimiento insulino-símil tipo 1 (IGF-1), dehidroepiandrosterona (DHEAS), cortisol, facto-res inflamatorios [proteína C reactiva (PCR), interleuquina 6 (IL-6) y factor de necrosis tu-moral (TNF-a)]. Las recomendaciones realiza-das están basadas en la evidencia científica disponible en la actualidad y la disponibilidad de la metodología apropiada para cada uno de los biomarcadores. (AU)

Sarcopenia is a progressive and generalized skeletal muscle disorder defined by decrease in the strength, quality and quantity of muscle mass as well as in muscle function. A biomarker is defined as a feature objectively measured and evaluated as an indicator of a normal biologic process, a pathogenic process or a pharmacologic response to therapeutic intervention. The biochemical markers proposed for the study of sarcopenia may be classified in two groups. The first group evaluates the musculoskeletal status, made up by myostatin/follistatin, N-terminal Type III Procollagen and the sarcopenia index. The second evaluates causal factors, where the measurement of the following is suggested: hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate (DHEAS), cortisol, inflammatory factors [C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a)]. The recommendations made are based on scientific evidence currently available and the appropriate methodology availability for each biomarker. (AU)

Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats

SUMMARY OBJECTIVE We aimed to explore the effects of neuropeptides ghrelin, obestatin, and vasoactive intestinal peptide (VIP) on seizures and plasma concentrations of neuroinflammation biomarkers including calcitonin gene-related peptide (CGRP), substance-P (SP), and interleukin-1 beta (IL-1β) in pentylenetetrazol-induced seizures in rats. METHODS Ghrelin (80 µg/kg), obestatin (1 µg/kg), VIP (25 ng/kg) or saline were administered to rats intraperitoneally 30 min before pentylenetetrazole (PTZ, 50 mg/kg) injections. Stages of epileptic seizures were evaluated by Racine's scale, and plasma CGRP, SP, and IL-1β concentrations were measured using ELISA. RESULTS Both obestatin and VIP shortened onset-time of generalized tonic-clonic seizure, respectively, moreover VIP also shortened the onset-time of first myoclonic-jerk induced by PTZ. While PTZ increased plasma CGRP, SP and IL-1β concentrations, ghrelin reduced the increases evoked by PTZ. While VIP further increased PTZ-evoked CGRP levels, it diminished IL-1β concentrations. However, obestatin did not change CGRP, SP, and IL-1β concentrations. CONCLUSION Our results suggest that ghrelin acts as an anticonvulsant, obestatin acts as a proconvulsant, and VIP has dual action on epilepsy. Receptors of those neuropeptides may be promising targets for epilepsy treatment.

RESUMO OBJETIVO Nosso objetivo foi explorar os efeitos dos neuropeptídeos grelina, obestatina e peptídeo intestinal vasoativo (VIP) nas convulsões e concentrações plasmáticas de biomarcadores neuroinflamatórios, incluindo peptídeo relacionado ao gene da calcitonina (CGRP), substância-P (SP) e interleucina-1 beta (IL-1β) em convulsões induzidas por pentilenotetrazol em ratos. MÉTODOS Grelina (80 µg/kg), obestatina (1 µg/kg), VIP (25 ng/kg) ou solução salina foram administrados a ratos intraperitonealmente 30 minutos antes de injeções de pentilenotetrazol (PTZ, 50 mg/kg). Os estágios das crises epilépticas foram avaliados pela escala de Racine e as concentrações plasmáticas de CGRP, SP e IL-1β foram medidas usando Elisa. RESULTADOS Tanto a obestatina quanto o VIP encurtaram o tempo de início da crise tônico-clônica generalizada, respectivamente. Além disso, o VIP também encurtou o tempo de início do primeiro impulso mioclônico induzido por PTZ. Enquanto o PTZ aumentou as concentrações plasmáticas de CGRP, SP e IL-1β, a grelina reduziu os aumentos evocados por PTZ. Enquanto o VIP aumenta ainda mais os níveis de CGRP evocados por PTZ, diminui as concentrações de IL-1β. No entanto, a obestatina não alterou as concentrações de CGRP, SP e IL-1β. CONCLUSÃO Nossos resultados sugerem que a grelina tem anticonvulsivante, a obestatina tem proconvulsivante e o VIP tem ação dupla na epilepsia. Receptores desses neuropeptídeos podem ser alvos promissores para o tratamento da epilepsia.

Ghrelin improves the fine structure of atrial natriuretic factor (ANF) granules and intercalated disc junctions in experimentally-induced myocardial infarction in rats / La grelina mejora las estructuras finas de los gránulos de factor natriurético atrial (ANF) y las uniones intercaladas de disco en el infarto de miocardio inducido experimentalmente en ratas

Ghrelin is a novel growth hormone-releasing peptide administered to treat myocardial infarction (MI). However, the underlying mechanism of its protective effects against MI remains unclear. A total of sixty healthy Sprague Dawley male rats were included. The first one is the sham-operated control group were the rats that underwent the same surgical used to induce MI but without tying the left anterior descending coronary artery (LAD) and received normal saline (0.5 ml) as vehicle; the second MI model group were rats with LAD ligation and received normal saline (0. 5 ml) and the third one is MI+ghrelin group were rats that were exposed to surgery to induce MI but received ghrelin (100 µ/kg, orally, 2x/day). At the end of the experiment after 21 days post-MI, rats were sacrificed and processed for ultrastructural demonstration. Our experiment showed that ghrelin inhibited cardiomyocyte apoptosis. Concomitant administration of ghrelin with MI treated rats of this study appeared to show a considerable protection of the atrial tissues. This study revealed that the sarcoplasm was occupied by normal myofibrils with clear striations and others appeared with minor disruption. Normal distribution of atrionatriuretic factor (ANF) granules and well preserved mitochondrial integrity (preserved cristae, normal size and shape), nucleus chromatin arrangement and striated pattern of clear bands (Z and H) compared to the MI group. Intact intercalated disc with clear identification of fully formed fascia adherence and desmosomes with a reconstruction of gap junction (nexus) was also noticed. Atrial myocytes after myocardial infarction is often associated with subsequent heart failure, which could lead to a fatal outcome. In a rat model of experimental myocardial infarction, peripheral ghrelin administration attenuated myocyte dysfunction, well-preserved desmosome, adherent and gap junction of the intercalated disc and normally distributed ANF granules.

La grelina es un nuevo péptido liberador de hormona de crecimiento administrado para tratar el infarto de miocardio (IM). Sin embargo, el mecanismo subyacente de sus efectos protectores contra el IM aún no se conocen. Se incluyeron un total de 60 ratas macho Sprague Dawley saludables. En el grupo control se incluyeron ratas que fueron sometidas a una cirugía utilizada para inducir el IM, pero sin ligar la arteria coronaria descendente anterior izquierda (ACDAI) y recibieron suero fisiológico normal (0,5 ml) como vehículo; el segundo grupo modelo de IM fueron ratas con ligadura de ACDAI y recibieron suero fisiológico normal (0,5 ml); el tercer grupo estuvo formado por ratas con IM + grelina, expuestas a la cirugía para inducir IM pero luego recibieron grelina (100 m/kg, oralmente, 2x/día). Al final del experimento, 21 días después del infarto de miocardio, los animales fueron sacrificados y procesados para el estudio ultraestructural. Nuestro experimento mostró que la grelina inhibe la apoptosis de los cardiomiocitos. La administración concomitante de grelina en ratas con IM parece indicar una protección considerable de los tejidos atriales. Además, el estudio reveló que el sarcoplasma estaba ocupado por miofibrillas normales con estriaciones claras y otras con una alteración menor. Se encontró una distribución normal de los gránulos del factor natriurético atrial (FNA) e integridad mitocondrial bien conservada (crestas conservadas, tamaño y forma normales), disposición de la cromatina del núcleo y patrón estriado de bandas claras (Z y H) en comparación con el grupo IM. También se observó un disco intercalado intacto con una clara identificación de la adherencia de la fascia completamente formada y desmosomas con una reconstrucción de la unión gap (nexo). Los miocitos atriales, después de un infarto de miocardio, a menudo se asocian con insuficiencia cardíaca posterior, que podría conducir a un desenlace fatal. En un modelo de rata de infarto de miocardio experimental, la administración de grelina periférica atenuó la disfunción de miocitos, con conservación del desmosoma, adherencia y unión de la brecha del disco intercalado y una distribución normal de los los gránulos de FNA.

Betatrophin Levels were Increased in Pregnant Women with or without Gestational Diabetes Mellitus and Associated with Beta Cell Function / Níveis de betatrofina aumentados em grávidas com ou sem diabetes mellitus gestacional e associados à função das células beta

Abstract Purpose betatrophin has been reported to boost β cell expansion in insulin resistant states. Pregnancy is a well-recognized physiological state of insulin resistance. Betatrophin levels in pregnant women and their relationships with metabolic variables remain to be elucidated. Methods A total of 49 pregnant women and 31 age-matched unpregnant women with normal glucose regulation (UP-NGR) were included. Among these subjects, according to results from 75 g oral glucose tolerance test (OGTT), 22 women were diagnosed as having gestational diabetes mellitus ( GDM ). Results Our study found that pregnant women, regardless of their glucose regulation status, had remarkably higher triglycerides (TG), total cholesterol (TC), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β). However, GDM patients had much lower HOMA-β compared with those of pregnant women with normal glucose regulation (P-NGR). Participants of the P-NGR group had almost 4 times higher levels of betatrophin than those of the UP-NGR group. Although betatrophin levels were lower in the GDM group than those of the P-NGR group, the difference did not reach statistical significance. Spearman correlation analysis showed that betatrophin levels were positively and significantly associated with total cholesterol, triglycerides, highdensity lipoprotein cholesterol (HDL-c), FINS and HOMA-β. However, adjustments of TC, TG and HDL-c eliminated the association between HOMA-β and betatrophin. Conclusions Pregnant women have significantly higher betatrophin levels in comparison to unpregnant women. Betatrophin levels are positively and significantly associated with β cell function and lipid levels. Furthermore, lipids may contribute to the association between betatrophin and β cell function.

Resumo Introdução Betatrofina tem sido relacionada à expansão de células β em estado de resistência à insulina. A gravidez é um conhecido estado fisiológico de resistência à insulina. Níveis de betatrofina em gestantes e sua relação com variáveis metabólicas ainda precisam ser esclarecidas. Métodos Um total de 49 gestantes e 31 não gestantes de mesma idade com níveis normais de glicose (UP-NGR) foram incluídas. Dentre elas, de acordo com os resultados da curva glicêmica, base em 75 g, 22 mulheres foram diagnosticadas com diabetes mellitus gestational ( DMG ). Resultados Nosso estudo identificou que gestantes, independente de seus níveis de glicose, tiveram notáveis níveis elevados de triglicerídeos (TG), colesterol (TC), insulina em jejum (FINS), HOMA-IR e HOMA-β. Contudo, pacientes com DMG tiveram bem menos HOMA-β se comparadas às gestantes com níveis normais de glicose ( P-NGR ). Participantes do grupo P-NGR tiveram níveis de betatrofina quase quarto vezes maiores ao das participantes do grupo UP-NGR. Embora os níveis de betatrofina sejam menores no grupo DMG do que no P-NGR, a diferença não obteve significância estatística. Análise da correlação de Spearman demonstrou que os níveis de betatrofina foram positiva e significativamente associados ao TC, TG, HDL-c (high-density lipoprotein cholesterol), FINS e HOMA-β. Contudo, ajustes em TC, TG e HDL-c eliminaram a associação entre HOMA-β e betatrofina. Conclusões Gestantes têm níveis de betatrofina significativamente maiores do que não gestantes. Níveis de betatrofina são positive e significativamente associados às células β funcionais e níveis de lipídeos. Além disso, lipídeos podem contribuir na associação entre betatrofina e células β funcionais.

Aspectos críticos do abuso de horm¶nios protéicos no exercício e no esporte: atualizaþÒo / [Critical aspects of peptide hormone abuse in exercise and sports: an update].

The hormonal abuse in physical exercise practioners is very common. Many pleople believe these substances can promote skeletal muscle hyperthrophy and improve physical fitness without health damaging effects. However, this is another myth that science unmasked. This article updates information regarding abuse of insulin, growth hormone, thyroid hormones, and erythropoitin. The peptide hormone abuse can cause motor paralysis, skeletal muscle damage and loss, diabetes mellitus, hypothyroidism, arterial hypertension, sweating, headaches, vomiting and enhances the risk for atherosclerosis, thrombosis, osteoporosis, and cancer.

Regulación de la hepcidina y homeostasis del hierro: avances y perspectivas / Regulation of hepcidin and iron homeostasis: progress and prospects

El estudio de los desórdenes genéticos del metabolismo del hierro, la identificación de sus transportadores y el descubrimiento de la hepcidina, hormona reguladora de la homeostasia del hierro, han contribuido grandemente a aumentar los conocimientos sobre este metabolismo y han cambiado sustancialmente la visión sobre las enfermedades relacionadas con alteraciones del metabolismo férrico. En la última década, no solo se han esclarecido elementos de la patogénesis de estas enfermedades, sino que ya se vislumbran aplicaciones terapéuticas de estos avances. Así, ya se habla de una nueva era basada en el tratamiento de los desórdenes de la homeostasia del hierro a través de la modulación de la hepcidina

The study of genetic disorders of iron metabolism, identification of transporters and the discovery of hepcidin- a hormone regulating iron homeostasis- have contributed greatly to increase awareness of this metabolism. Substantially, the vision on diseases related to disorders of iron metabolism has been changed. In the last decade, elements of the pathogenesis of these diseases have not only been clarified, but therapeutic applications of these advances are looming. Thus, there are expectations of a new era based on the treatment of iron homeostasis disorders through hepcidin modulation

Appetite-related hormone levels in obese women with and without binge eating behavior / Hormônios reguladores do apetite em mulheres obesas com e sem compulsão alimentar

OBJECTIVE: The aim of this study was to evaluate serum levels of appetite-related hormones (peptide YY3-36, total ghrelin, leptin and insulin) before and after consumption of a meal in obese women with and without binge eating episodes and normal weight women. METHODS: Twenty-five women aged 32-50 years were invited to participate in this study, including 9 normal weight women without binge eating episodes (20-25kg/m², group 1), 9 obese women with binge eating episodes (³30kg/m², group 2), and 7 obese women without binge eating episodes (group 3). Four blood samples were collected from each participant, one being 60 minutes before and three being 15, 45 and 90 minutes after a meal. The composition of the meal was 55 percent carbohydrates, 15 percent protein and 30 percent lipids. RESULTS: Group 3 presented increased HOMA-IR (M=2.5, SD=1.04) when compared with group 1 (M=1.5, SD=0.53) and group 2 (M=1.8, SD=0.58), p=0.04. Body mass index (p<0.0001), leptin (p<0.0001) and insulin (p=0.01) were higher in group 3 than in the other groups before and after the meal. Additionally, total ghrelin (p=0.003) and PYY3-36 (p=0.02) levels were lower in group 2 than in the other groups before and after the meal. After adjustment for body mass index, only the lower PYY3-36 level of group 2 remained statistically different from the other groups (p=0.01). CONCLUSION: Our study suggests that lower levels of PYY 3-36 are associated with binge eating in obese women.

OBJETIVO: O objetivo deste estudo foi avaliar, antes e após a refeição, as concentrações séricas de hormônios ligados ao controle do apetite (peptídeo YY3-36, grelina total, leptina e insulina) em mulheres obesas com e sem episódios de compulsão alimentar e compará-las às mulheres de peso normal. MÉTODOS: Vinte e cinco mulheres com idade entre 32 e 50 anos foram convidadas a participar deste estudo, incluindo 9 mulheres com peso normal (20-25kg/m²) sem episódios de compulsão alimentar (grupo 1), 9 mulheres obesas (³30 kg/m²) com episódios de compulsão alimentar (grupo 2) e 7 mulheres obesas sem episódios de compulsão alimentar (grupo 3). Foram coletadas quatro amostras de sangue pós-prandiais a 60 minutos (1 hora antes), bem como 15, 45 e 90 minutos após uma refeição composta de 55 por cento de carboidratos, 15 por cento de proteínas e 30 por cento de lipídeos. RESULTADOS: O maior HOMA-IR foi observado no grupo 3 (M=2,5, DP=1,04) quando comparado ao grupo 1 (M=1,5, DP=0,53) e ao grupo 2 (M=1,8, DP=0,58), p=0,04. O índice de massa corporal (p<0,0001), a leptina (p<0,0001) e a insulina (p=0,01) foram maiores no grupo 3 antes e após a refeição. A grelina total (p=0,003) e o PYY3-36 (p=0,02) foram menores no grupo 2 antes e após a refeição. Após o ajuste do índice de massa corporal, apenas a baixa concentração de PYY3-36 no grupo 2 manteve-se estatisticamente diferente entre os grupos (p=0,01). CONCLUSÃO: Este estudo sugere que níveis baixos do PYY-3-36 estejam associados à compulsão alimentar em mulheres obesas.

Comparação da acurácia de preditores de mortalidade na pneumonia associada à ventilação mecânica / Comparing the accuracy of predictors of mortality in ventilator-associated pneumonia

OBJETIVO: Níveis de procalcitonina, midregional pro-atrial natriuretic peptide (MR-proANP, pró-peptídeo natriurético atrial midregional),, C-terminal provasopressin (copeptina), proteína C reativa (CRP) e escore do Sequential Organ Failure Assessment (SOFA) são associados a gravidade e descritos como preditores de desfechos na pneumonia associada a ventilação mecânica (PAVM). Este estudo procurou comparar o valor preditivo de mortalidade desses biomarcadores na PAVM. MÉTODOS: Estudo observacional com 71 pacientes com PAVM. Níveis de procalcitonina, MR-proANP, copeptina e PCR, bem como escore de SOFA foram obtidos no dia do diagnóstico de PAVM, designado dia zero (D0), e no quarto dia de tratamento (D4) Os pacientes receberam tratamento antimicrobiano empírico, com modificações baseadas nos resultados de cultura. Os pacientes que morreram antes de D28 foram classificados como não sobreviventes. RESULTADOS: Dos 71 pacientes, 45 sobreviveram. Dos 45 sobreviventes, 35 (77,8 por cento) receberam tratamento antimicrobiano adequado, comparados com 18 (69,2 por cento) dos 26 não sobreviventes (p = 0,57). Os sobreviventes apresentaram valores significativamente mais baixos em todos os biomarcadores estudados, inclusive no escore de SOFA (exceto PCR) em D0 e D4. Em D0 e D4, a área sob a curva ROC foi maior para procalcitonina. Em D0, MR-proANP teve a maior razão de verossimilhança positiva (2,71) e valor preditivo positivo (0,60), mas a procalcitonina apresentou o maior valor preditivo negativo (0,87). Em D4, a procalcitonina apresentou a maior razão de verossimilhança positiva (3,46), o maior valor preditivo positivo (0,66) e o maior valor preditivo negativo (0,93). CONCLUSIONS: Os biomarcadores procalcitonina, MR-proANP e copeptina podem predizer mortalidade na PAVM, assim como o escore de SOFA. A procalcitonina tem o maior poder preditivo de mortalidade na PAVM.

OBJECTIVE: Levels of procalcitonin, midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal provasopressin (copeptin), and C-reactive protein (CRP), as well as Sequential Organ Failure Assessment (SOFA) scores, are associated with severity and described as predictors of outcome in ventilator-associated pneumonia (VAP). This study sought to compare the predictive value of these biomarkers for mortality in VAP. METHODS: An observational study of 71 patients with VAP. Levels of procalcitonin, MR-proANP, copeptin, and CRP, together with SOFA scores, were determined at VAP onset, designated day 0 (D0), and on day 4 of treatment (D4). Patients received empirical antimicrobial therapy, with modifications based on culture results. Patients who died before D28 were classified as nonsurvivors. RESULTS: Of the 71 patients evaluated, 45 were classified as survivors. Of the 45 survivors, 35 (77.8 percent) received appropriate antimicrobial therapy, compared with 18 (69.2 percent) of the 26 nonsurvivors (p = 0.57). On D0 and D4, the levels of all biomarkers (except CRP), as well as SOFA scores, were lower in eventual survivors than in eventual nonsurvivors. For D0 and D4, the area under the ROC curve was largest for procalcitonin. On D0, MR-proANP had the highest positive likelihood ratio (2.71) and positive predictive value (0.60), but procalcitonin had the highest negative predictive value (0.87). On D4, procalcitonin had the highest positive likelihood ratio (3.46), the highest positive predictive value (0.66), and the highest negative predictive value (0.93). CONCLUSIONS: The biomarkers procalcitonin, MR-proANP, and copeptin can predict mortality in VAP, as can the SOFA score. Procalcitonin alone has the greatest predictive power for such mortality.

Metabolic and nutritional interfaces in polycystic ovary syndrome: considerations regarding obesity and dietary macronutrients / Interfaces nutricionales y metabólicas en el síndrome del ovario policístico: el papel de la, obesidad y de los macronutrientes de la dieta

El Síndrome del Ovario Poliquístico (SOP) es un desorden endocrino que ocurre entre las mujeres en edad reproductiva. Se caracteriza por irregularidad menstrual, anovulación crónica, infertilidad e hiperandrogenismo. La prevalencia de la obesidad es alta entre mujeres con el SOP y sus causas aún no están esclarecidas. Anormalidades en el gasto energético y en la respuesta disminuida de las hormonas gastrointestinales responsables por el control de la ingestión alimentaria, especialmente la grelina son posibles hipótesis para explicar la obesidad asociada al SOP. Los efectos de la composición dietética en el SOP aún están poco explorados. Es posible que los ácidos grasos poliinsaturados (PUFA) mejoran la sensibilidad insulínica y que dietas hiperproteicas potencializan la pérdida de peso y mejoran la función reproductiva. Sin embargo, las evidencias actuales no son suficientes para determinar las características dietéticas mas adecuadas para el SOP. La conducta dietética debe enfocar la pérdida de peso con dietas nutricionalmente completas y balanceadas.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women at reproductive age. Its classical form is characterized by menstrual irregularities, chronic anovulation, infertility, and hyperandrogenism. The prevalence of obesity is high among women with POS and its causes have not been fully clarified. Hypotheses have been raised suggesting the possible presence of both abnormal energy expenditure and a reduced response of the gastrointestinal hormones responsible for the control of food ingestion, especially ghrelin. The specific effects of diet composition on POS have been little explored. It has been suggested that po-lyunsaturated fatty acids may improve insulin sensitivity and that high-protein diets may potentiate weight loss and improve reproductive function. However, current evidence is insufficient to determine the optimum composition of a diet for POS patients. The dietary conduct should focus on weight loss to be achieved with nutritionally complete and balanced diets.

Leptina e insulina sérica en adultos con sobrepeso y obesos en régimen hipocalórico con alto contenido de carbohidratos complejos / Serum leptin and insulin in obese adults on hypocaloric dietary regimen of high complex carbohydrate content

En situaciones de cambios en el peso, la evidencia sobre la relación entre la leptina y la insulina con el contenido de grasa corporal no es concluyente. Se planteó establecer asociaciones entre leptina e insulina (ELISA) y pérdida de peso (antropometría) durante un régimen hipocalórico alto en fibra, en 71 individuos (sobrepeso/ obesos), al inicio (I), a dos (2s) y a seis semanas (6s) del régimen. Se aplicaron pruebas no paramétricas para muestras independientes y relacionadas. Hubo disminución significativa de la leptina entre I, 2s y 6s, similar entre sobrepeso y obesidad, normalizándose a las 6s (sobrepeso fueron normales a las 2s y obesos a las 6s). Aumentó la prevalencia de valores normales (leptina <15 ng/mL) durante el régimen. La leptina fue significativamente mayor en obesos que en los con sobrepeso y en mujeres que en hombres, sin diferencias significativas por género para la insulina. Asociación significativa entre leptina e indicadores de adiposidad (índice de masa corporal, circunferencia abdominal). A las 2s, hubo correlación positiva entre leptina e insulina, no evidente a las 6s. El régimen basado en el consumo de fibra fue eficiente para lograr cambios en los parámetros antropométricos y bioquímicos, en especial, una disminución de la leptina.

Leptin acts as a regulatory signal for food intake, body energy balance, body fat content and body weight stability. In order to establish associations among serum leptin, serum insulin and weight loss, 71 obese or overweight adults were assessed by anthropometry and serum determination of leptin at the beginning (B), two weeks (2w) and six weeks (6w) after consuming a dietary regime based on complex carbohydrates intake. Data was analyzed by non parametrical tests for independent and related samples. There was a significant decrease of leptin among B, 2w and 6w of similar nature between overweight and obese participants, with all of them reaching normal values at 6w (overweight at 2w and obese at 6 w). Prevalence of normal leptin values (<15 ng/mL) increased among B, 2w and 6w. Leptin levels were significantly higher in obese vs. overweight and in women vs. men with no differences in serum glucose or insulin by sex. There was a significant association between leptin and adiposity indicators (body mass index and abdominal circumference). At 2w, but not at 6w, a positive correlation between leptin and insulin was found. A dietary regime based on increased consumption of complex carbohydrate (fiber) was efficient to induce favorable changes in anthropometrical and biochemical indicators, especially serum leptin.

Tumores endócrinos del páncreas / Endocrine tumors of the pancreas

Multiple endocrine neoplasia (MEN) is a rare familial disorder that affects multiple endocrine organs. it is inherited in an autosomal dominant pattern with variable penetrance. There are two distinct types of MEN. Dominantly inherited neoplasia are believed to occur from the recessive loss of tumor suppressor gene function. The first mutational event affects the germ cell, is hereditary, and predisposes to neoplasia. Because tumors occur in multiple organs in MEN, the second mutational evento probably occurs in common precursor cells, such as the amine precursor uptake and decarboxylation cells (APUD). The gene locus for tupe 1 MEN has been mapped to cromosome 11q. Type 1 organs affected: parathyroids, pancreas and pituitary. The gene locus for type 2 MEN is thought to be located for chromosome 10, (other organs). Fifty to 60 % of patients with type 1 MEN have pancreaticislet cell tumors. Insulinomas are tumors that originate in the beta cells of the islets of Langerhans, which compose the APUD system, the meaning of which is: A=Amino, P=Precursor, U=Uptake, D=Decarboxylation. The cells fo the APUD system have common cytochemical characteristics with the ability to secret polypeptides and amines. Symptoms are related to the peptide secreted by the tumor, and some tumors can produce multiple peptides. Gastrinomas comprise about 60 % of type 1 MEN-associated islet cell tumors. Gastric acid hypersecretion results from excess gstrin secretion and causes multiple gastric and duodenal ulcers (Zollinger-Ellison syndrome). The author describe an experience with this pathology with special reference to diagnostic methods, treatment, follow-up, laboratory studies and localization of the tumor.

Effect of one month ketoconazole treatment on GH, cortisol and ACTH release after ghrelin, GHRP-6 and GHRH administration in patients with cushing’s disease

GH responses to ghrelin, GHRP-6, and GHRH in Cushing’s disease (CD) are markedly blunted. There is no data about the effect of reduction of cortisol levels with steroidogenesis inhibitors, like ketoconazole, on GH secretion in CD. ACTH levels during ketoconazole treatment are controversial. The aims of this study were to compare the GH response to ghrelin, GHRP-6, and GHRH, and the ACTH and cortisol responses to ghrelin and GHRP-6 before and after one month of ketoconazole treatment in 6 untreated patients with CD. Before treatment peak GH (mg/L; mean ± SEM) after ghrelin, GHRP-6, and GHRH administration was 10.0 ± 4.5; 3.8 ± 1.6, and 0.6 ± 0.2, respectively. After one month of ketoconazole there was a significant decrease in urinary cortisol values (mean reduction: 75 percent), but GH responses did not change (7.0 ± 2.0; 3.1 ± 0.8; 0.9 ± 0.2, respectively). After treatment, there was a significant reduction in cortisol (mg/dL) responses to ghrelin (before: 30.6 ± 5.2; after: 24.2 ± 5.1). No significant changes in ACTH (pg/mL) responses before (ghrelin: 210.9 ± 69.9; GHRP-6: 199.8 ± 88.8) and after treatment (ghrelin: 159.7 ± 40.3; GHRP-6: 227 ± 127.2) were observed. In conclusion, after short-term ketoconazole treatment there are no changes in GH or ACTH responses, despite a major decrease of cortisol levels. A longer period of treatment might be necessary for the recovery of pituitary function.

Na doença de Cushing (DC), as respostas do GH à ghrelina, ao GHRP-6 e ao GHRH estão diminuídas. Não existem dados sobre o efeito da redução dos níveis de cortisol, após cetoconazol, na secreção de GH na DC. Nessa situação, os níveis de ACTH são variáveis. Os objetivos do estudo são comparar as respostas do GH à administração de ghrelina, GHRP-6 e GHRH, e de ACTH e cortisol à ghrelina e ao GHRP-6 antes e após um mês de tratamento com cetoconazol em 6 pacientes com DC não tratados. Antes do tratamento, o pico de GH (mg/L; média ± EPM) após a administração de ghrelina, GHRP-6 e GHRH foi de 10,0 ± 4,5; 3,8 ± 1,6 e 0,6 ± 0,2, respectivamente. Após um mês de cetoconazol, ocorreu diminuição significante do cortisol urinário (redução média: 75 por cento), mas as respostas de GH permaneceram inalteradas (7,0 ± 2,0; 3,1 ± 0,8; 0,9 ± 0,2, respectivamente). Após o tratamento, houve redução da resposta de cortisol (mg/dL) à ghrelina (antes: 30,6 ± 5,2; após: 24,2 ± 5,1), mas não ocorreram mudanças nas respostas de ACTH (pg/mL) (ghrelina antes: 210,9 ± 69,9; após: 159,7 ± 40,3; GHRP-6 antes: 199,8 ± 88,8; após: 227 ± 127,2). Assim, o tratamento a curto prazo com cetoconazol não modificou as respostas de GH ou ACTH, apesar da redução do cortisol. Para a recuperação da função hipofisária deve ser necessário um período de tratamento maior.

Novel mechanisms of growth hormone regulation: growth hormone-releasing peptides and ghrelin

Growth hormone secretion is classically modulated by two hypothalamic hormones, growth hormone-releasing hormone and somatostatin. A third pathway was proposed in the last decade, which involves the growth hormone secretagogues. Ghrelin is a novel acylated peptide which is produced mainly by the stomach. It is also synthesized in the hypothalamus and is present in several other tissues. This endogenous growth hormone secretagogue was discovered by reverse pharmacology when a group of synthetic growth hormone-releasing compounds was initially produced, leading to the isolation of an orphan receptor and, finally, to its endogenous ligand. Ghrelin binds to an active receptor to increase growth hormone release and food intake. It is still not known how hypothalamic and circulating ghrelin is involved in the control of growth hormone release. Endogenous ghrelin might act to amplify the basic pattern of growth hormone secretion, optimizing somatotroph responsiveness to growth hormone-releasing hormone. It may activate multiple interdependent intracellular pathways at the somatotroph, involving protein kinase C, protein kinase A and extracellular calcium systems. However, since ghrelin has a greater ability to release growth hormone in vivo, its main site of action is the hypothalamus. In the current review we summarize the available data on the: a) discovery of this peptide, b) mechanisms of action of growth hormone secretagogues and ghrelin and possible physiological role on growth hormone modulation, and c) regulation of growth hormone release in man after intravenous administration of these peptides.

Insulina, leptina y hormona de crecimiento y su relación con índice de masa corporal e índice de obesidad en adolescentes / Serum Insulin, leptin and growth hormone levels are associated with body mass index and obesity index in adolescents

La leptina, insulina y hormona de crecimiento influyen en la masa grasa, composición corporal y distribución grasa. El propósito de este estudio fue determinar la relación entre los niveles de insulina, leptina y hormona de crecimiento con parámetros antropométricos y lipídicos en adolescentes. Se estudiaron 95 adolescentes entre 13 y 18 años. Se realizó una historia clínico-nutricional donde se midió el índice de masa corporal (IMC) y los pliegues subcutáneos. Se determinaron los niveles basales de glicemia, triglicéridos, colesterol total, HDL-C, LDL-C y VLDL-C, insulina, leptina y hormona de crecimiento. Los niveles de leptina e insulina se relacionaron positivamente con el IMC y el Índice de Obesidad (IOB). La insulina, leptina e indicadores de obesidad se relacionaron en forma negativa con la hormona de crecimiento. El 52% de los adolescentes con IMC≥21,09 Kg/m2 e IOB >42,02 mm se consideraron metabólicamente obesos, debido a que comparados con los adolescentes normales, presentaron niveles elevados de insulina (18,68± 1,52 vs 10,08± 0,38 m U/ml), HOMA IR (3,34± 0,24 vs 1,76± 0,07), leptina (16,30± 1,24 vs 8,11± 1,32 ng/dl) y triglicéridos (78,56± 4,38 vs 64,39± 5,48 mg/dl) y disminución de HDL-C (39,09± 1,27 vs 43,30± 2,38 mg/dl). Estas mismas alteraciones se observaron en adolescentes obesos en quienes se produjo además una disminución significativa de la hormona de crecimiento. Se concluye que en los adolescentes estudiados existió una serie de factores de riesgo como hiperinsulinemia, hiperleptinemia y hormona de crecimiento disminuida relacionada con marcadores de obesidad, alteraciones lipídicas e insulino resistencia, lo cual puede conducir a la aparición temprana de diabetes tipo 2 y enfermedad cardiovascular.

Leptin, insulin and growth hormone levels seem to regulate body composition, fat distribution and fat mass. The purpose of this study was to determine the relationship among insulin, leptin and growth hormone levels in a group of adolescents. Ninety five adolescents (31 boys and 64 girls) between 13 and 18 y. of age were studied. A medical and nutritional history was made which included body mass index (BMI) and subcutaneous skinfolds measurements. Basal levels of glucose, triglycerides, total cholesterol, HDL-C, LDL-C, VLDL-C, leptin, insulin and growth hormone were determined. The leptin and insulin levels were positively associated with body mass index (BMI) and obesity index (OBI). Insulin, leptin and obesity markers were negatively associated with growth hormone level. Fifty two percent of the adolescents with BMI ≥21.09 kg/m2 were considered metabolically obese because they had elevated levels of insulin (18.68 ± 1.52 vs. 10.08 ± 0.38 m U/ml), HOMA IR (3.34± 0.24 vs. 1.76± 0.07), leptin (16.30± 1.24 vs. 8.11± 1.32 ng./dl) and triglycerides (78.56± 4.38 vs 64.39± 5.48 mg/dl) and lower levels of HDL-C (39.09± 1.27 vs 43.30± 2.38 mg/dl), compared with normal group. The same alterations were observed in the obese group, in which significative decrease in growth hormone level was added. We conclude that hyperinsulinemia, hyperleptinemia and low growth hormone levels, may be established as risk factors related to obesity markers, lipid alterations and insulin resistance that can lead to an early development of Type II diabetes and cardiovascular disease.

La ghrelina y su importancia con el eje gastrohipotalámico / Ghrelin and the gastro-hypothalamic axis

La obesidad se considera una de las enfermedades más importantes en la medida que acarrea gran morbilidad y mortalidad. El conocimiento de los mecanismos que intervienen en la saciedad, el peso corporal y el gasto de energía ha permitido el descubrimiento de hormonas relacionadas con el eje gastrohipotalámico, encargado de regular la saciedad y otros procesos que participan en la obesidad. La ghrelina, una hormona de secreción predominantemente gástrica, dio luz para comprender estos mecanismos, pues se trata de una hormona que regula la saciedad y el peso corporal por medio de mecanismos centrales mediados por el neuropéptido Y y la proteína relacionada con el agutí. En este artículo se revisan los aspectos fundamentales de esta hormona y de sus efectos en diversos órganos y sistemas.

Obesity is currently considered one of the most important diseases worldwide due to its high morbidity and mortality rates. The mechanisms involved in the control of satiation, body weight and energy expenditure has led to the discovery of new hormones that participate in the gastrichypothalamic axis in charge of regulating satiation and other obesity-related processes. Ghrelin a novel hormone secreted mainly by gastric tissue, has shed some light on this mechanism. It is a hormone that regulates satiation and body weight by centrally mediated mechanisms, involving neuropeptide Y and Agouti associated proteins. The present review focuses on some important physiological aspects of this hormone.

From growth hormone-releasing peptides to ghrelin: discovery of new modulators of GH secretion

A secreção de hormônio de crescimento (HC) é modulada pelo hormônio liberador de HC e pela somatostatina. Na ultima década foi descoberto um terceiro mecanismo de controle, envolvendo os secretagogos de HC. A ghrelina é um peptídeo acilado, descoberto recentemente, que é produzido no estômago, porém também é sintetizado no hipotálamo. Este peptídeo é capaz de liberar HC, além de aumentar a ingestão alimentar. A ghrelina endógena parece amplificar o padrão básico de secreção de HC, ampliando a resposta do somatotrófo ao hormônio liberador de HC. Este peptídeo estimula múltiplas vias intracelulares interdependentes no somatotrófo, envolvendo a proteína quinase C, proteína quinase A e sistemas moduladores de cálcio extracelular. Entretanto, como a liberação de HC induzida pela ghrelina in vivo é mais acentuada que in vitro, seu local de atuação predominante é no hipotálamo. Nesse artigo apresentamos uma revisão sobre a descoberta da ghrelina, os dados existentes sobre os mecanismos de ação e possível papel fisiológico dos secretagogos de HC e da ghrelina na secreção de HC e, finalmente, os efeitos da administração endovenosa destes peptídeos sobre a secreção de HC no homem.

Concentraciones plasmáticas de adiponectina en individuos normales y obesos correlacionadas con el perfil de lípidos plasmáticos / Plasma adiponectin concentration in normal weight and obese individual is associated with profile of plasma lipids

La adiponectina es una proteína del tejido adiposo que mejora la sensibilidad a la insulina y posee propiedades antiaterogénicas. Los niveles circulantes son más bajos en hombres que en mujeres y se encuentran disminuidos en la obesidad, diabetes tipo 2 y enfermedad cardiovascular. Este estudio investiga la relación entre los niveles de adiponectina con los líquidos plasmáticos y la resistencia a la insulina, en 180 individuos normales y obesos. Medimos adiponectina, mediante radioinmunoanálisis, colesterol total sérico, colesterol de HDL (C-HDL), triglicéricos, glicemia de ayuno e insulina plasmática. Las mujeres tenían la adiponectina más alta que los hombres (8,45 ± 3,82 versus 6,10 ± 2,62) y la resistencia a la insulina medida por HOMA IR se correlacionó negativamente con la adiponectina tanto en obesos como en no obesos, independientemente del índice de masa corporal (IMC). Asimismo, hubo una correlación positiva entre adiponectina y C-HDL (p = 0,01) y negativa con los triglicéridos (p = 0,05). Estos resultados indican que los niveles elevados de triglicéridos y los bajos niveles de C-HDL se asocian con concentraciones plasmáticas disminuidas de adiponectina. Se requieren mayores estudios para determinar si la adiponectina es la causante de estas anormalidades lipídicas.