Ghrelin and growth hormone secretagogues (GHS): modulation of growth hormone secretion and therapeutic applications

Growth hormone-releasing hormone (GHRH) and somatostatin modulate growth hormone (GH) secretion. A third mechanism was discovered in the last decade, involving the action of growth hormone secretagogues (GHS). Ghrelin, the endogenous ligand of the GHS-receptor, is an acylated peptide mainly produced by the stomach, but also synthesized in the hypothalamus. This compound increases both GH release and food intake. Endogenous ghrelin might amplify the basic pattern of GH secretion, optimizing somatotroph responsiveness to GHRH, activating multiple interdependent intracellular pathways. However, its main site of action is the hypothalamus. In the current paper it is reviewed the available data on the discovery of this peptide, the mechanisms of action and possible physiological roles of the GHS and ghrelin on GH secretion, and finally, the possible therapeutic applications of these compounds.A secreção do hormônio de crescimento (GH) é modulada pelo hormônio liberador de hormônio de crescimento (GHRH) e pela somatostatina. Na última década foi descoberto um terceiro mecanismo de controle, envolvendo os secretagogos de GH (GHS). A ghrelina, o ligante endógeno do receptor dos GHS, é um peptídeo acilado produzido no estômago, que também é sintetizado no hipotálamo. Este peptídeo é capaz de liberar GH, além de aumentar a ingesta alimentar. A ghrelina endógena parece amplificar o padrão básico de secreção de GH, ampliando a resposta do somatotrofo ao GHRH, estimulando múltiplas vias intracelulares interdependentes. Entretanto, seu local de atuação predominante é o hipotálamo. Neste trabalho, será apresentada revisão sobre a descoberta da ghrelina, os mecanismos de ação e o possível papel fisiológico dos GHS e da ghrelina na secreção de GH e, finalmente, as possíveis aplicações terapêuticas destes compostos.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Endothelial Wall Thickness, Cardiorespiratory Fitness And Inflammatory Markers In Obese And Non-obese Adolescents.

Increased carotid intima-media thickness (c-IMT) is considered a marker of early-onset atherosclerosis and it has been found in obese children and adolescents, but the risk factors associated with this population remain to be elucidated. To compare and verify the relationship between c-IMT, metabolic profile, inflammatory markers, and cardiorespiratory fitness in obese and non-obese children and adolescents. Thirty-five obese subjects (19 boys) and 18 non-obese subjects (9 boys), aged 10-16 years, were included. Anthropometry, body composition, blood pressure, maximal oxygen consumption (VO2max), and basal metabolic rate were evaluated. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, C-reactive protein (CRP), and adiponectin were assessed. c-IMT was measured by ultrasound. The results showed that c-IMT, triglycerides, insulin, HOMA-IR, and CRP values were significantly higher in the obese group than in the non-obese group, and high-density lipoprotein cholesterol (HDL-c), adiponectin, and VO2max values were significantly lower in the obese group than in the non-obese group. The c-IMT was directly correlated with body weight, waist circumference, % body fat, and HOMA-IR and inversely correlated with % free fat mass, HDL-c, and VO2max. Our findings show that c-IMT correlates not only with body composition, lipids, insulin resistance, and inflammation but also with low VO2max values in children and adolescents.1847-5

Effects of a Community Population Health Initiative on Blood Pressure Control in Latinos.

Background Hypertension remains one of the most important, modifiable cardiovascular risk factors. Yet, the largest minority ethnic group (Hispanics/Latinos) often have different health outcomes and behavior, making hypertension management more difficult. We explored the effects of an American Heart Association-sponsored population health intervention aimed at modifying behavior of Latinos living in Texas. Methods and Results We enrolled 8071 patients, and 5714 (65.7%) completed the 90-day program (58.5 years ±11.7; 59% female) from July 2016 to June 2018. Navigators identified patients with risk factors; initial and final blood pressure ( BP ) readings were performed in the physician\u27s office; and interim home measurements were recorded telephonically. The intervention incorporated home BP monitoring, fitness and nutritional counseling, and regular follow-up. Primary outcomes were change in systolic BP and health-related quality of life. Using a univariate paired-samples pre-post design, we found an average 5.5% (7.6-mm Hg) improvement in systolic BP (139.1 versus 131.5, t=10.32,

Characterization of a Copper Powder for Heat Pipe Wick Applications

In powder metallurgy, it is necessary to know the powder's nature to understand how the processing of a powder occurs. In this paper, a characterization of a copper powder for heat pipe wick applications was experimentally done. The copper powder manufacturing method was atomization. This metallic powder was characterized by Scanning Electron Microscopy (SEM), X-Ray Fluorescence Spectrometry (ED-XRF), and Laser Diffraction Granulometry. As a result, the purity and the shape are compatible with the powder manufacturing method and great for wicks. Also, the copper powder has a unimodal distribution that is excellent for capillary structures

Heterologous expression and functional characterization of a GH10 endoxylanase from \u3ci\u3eAspergillus fumigatus\u3c/i\u3e var. \u3ci\u3eniveus\u3c/i\u3e with potential biotechnological application

Xylanases decrease the xylan content in pretreated biomass releasing it from hemicellulose, thus improving the accessibility of cellulose for cellulases. In this work, an endo-β-1,4-xylanase from Aspergillus fumigatus var. niveus (AFUMN-GH10) was successfully expressed. The structural analysis and biochemical characterization showed this AFUMN-GH10 does not contain a carbohydrate-binding module. The enzyme retained its activity in a pH range from 4.5 to 7.0, with an optimal temperature at 60°C. AFUMN-GH10 showed the highest activity in beechwood xylan. The mode of action of AFUMNGH10 was investigated by hydrolysis of APTS-labeled xylohexaose, which resulted in xylotriose and xylobiose as the main products. AFUMN-GH10 released 27% of residual xylan from hydrothermally-pretreated corn stover and 14% of residual xylan from hydrothermally-pretreated sugarcane bagasse. The results showed that environmentally friendly pretreatment followed by enzymatic hydrolysis with AFUMN-GH10 in low concentration is a suitable method to remove part of residual and recalcitrant hemicellulose from biomass

Characteristics of two conditioning regimens cyclophosphamide plus antithymocyte globulin versus cyclophosphamide plus busulfan in allogeneic stem cell transplantation for severe aplastic anemia

Universidade Federal de São Paulo, São Paulo, BrazilHosp Santa Marcelina, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection.

BackgroundChagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections. In a target-based drug discovery program guided by x-ray crystallography, we identified the 4-aminopyridyl-based series of CYP51 inhibitors as being efficacious versus T.cruzi in vitro; two of the most potent leads, 9 and 12, have now been evaluated for toxicity and efficacy in mice.Methodology/principal findingsBoth acute and chronic animal models infected with wild type or transgenic T. cruzi strains were evaluated. There was no evidence of toxicity in the 28-day dosing study of uninfected animals, as judged by the monitoring of multiple serum and histological parameters. In two acute models of Chagas disease, 9 and 12 drastically reduced parasitemia, increased survival of mice, and prevented liver and heart injury. None of the compounds produced long term sterile cure. In the less severe acute model using the transgenic CL-Brenner strain of T.cruzi, parasitemia relapsed upon drug withdrawal. In the chronic model, parasitemia fell to a background level and, as evidenced by the bioluminescence detection of T. cruzi expressing the red-shifted luciferase marker, mice remained negative for 4 weeks after drug withdrawal. Two immunosuppression cycles with cyclophosphamide were required to re-activate the parasites. Although no sterile cure was achieved, the suppression of parasitemia in acutely infected mice resulted in drastically reduced inflammation in the heart.Conclusions/significanceThe positive outcomes achieved in the absence of sterile cure suggest that the target product profile in anti-Chagasic drug discovery should be revised in favor of safe re-administration of the medication during the lifespan of a Chagas disease patient. A medication that reduces parasite burden may halt or slow progression of cardiomyopathy and therefore improve both life expectancy and quality of life

Endothelial wall thickness, cardiorespiratory fitness and inflammatory markers in obese and non-obese adolescents

Background: Increased carotid intima-media thickness (c-IMT) is considered a marker of early-onset atherosclerosis and it has been found in obese children and adolescents, but the risk factors associated with this population remain to be elucidated. Objective : To compare and verify the relationship between c-IMT, metabolic profile, inflammatory markers, and cardiorespiratory fitness in obese and non-obese children and adolescents. Method : Thirty-five obese subjects (19 boys) and 18 non-obese subjects (9 boys), aged 10-16 years, were included. Anthropometry, body composition, blood pressure, maximal oxygen consumption (VO2max), and basal metabolic rate were evaluated. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, C-reactive protein (CRP), and adiponectin were assessed. c-IMT was measured by ultrasound. Results: The results showed that c-IMT, triglycerides, insulin, HOMA-IR, and CRP values were significantly higher in the obese group than in the non-obese group, and high-density lipoprotein cholesterol (HDL-c), adiponectin, and VO2max values were significantly lower in the obese group than in the non-obese group. The c-IMT was directly correlated with body weight, waist circumference, % body fat, and HOMA-IR and inversely correlated with % free fat mass, HDL-c, and VO2max. Conclusions : Our findings show that c-IMT correlates not only with body composition, lipids, insulin resistance, and inflammation but also with low VO2max values in children and adolescents

O papel do enfermeiro na prevenção das lesões na síndrome do pé diabético

The aim was to identify the role of nurses in preventive care for Diabetic Foot injuries. Descriptive-exploratory study, of a quantitative nature. Carried out in a health clinic located in the city of São Paulo, with 65 diabetic patients, between 18 and 90 years old. Among the study participants, the highest percentage of those who showed signs and symptoms of Diabetic Foot Syndrome were among those who had the diagnosis a longer time ago, had greater resistance to changes in habits and adherence to treatment, did not follow the guidelines on foot care and/or had other associated chronic diseases. The nurse is fundamental in early diagnosis, interventions and education on preventive care. The prevention of Diabetic Foot complications depends on the commitment, communication and training of the multidisciplinary team to reduce amputations and morbidity and mortality of diabetics.Objetivou-se identificar o papel do enfermeiro nos cuidados preventivos das lesões do Pé Diabético. Estudo descritivo-exploratório, de natureza quantitativa. Realizado em uma clínica de saúde localizada no município de São Paulo, com 65 pacientes diabéticos, entre 18 e 90 anos. Entre os participantes do estudo, a maior porcentagem dos que apresentavam sinais e sintomas da Síndrome do Pé Diabético, estavam entre os que tiveram o diagnóstico há mais tempo, possuíam maior resistência a mudanças de hábito e adesão ao tratamento, não seguiam as orientações sobre os cuidados com os pés e/ou possuíam outras doenças crônicas associadas. O enfermeiro é fundamental no diagnóstico precoce, intervenções e educação sobre cuidados preventivos. A prevenção das complicações do Pé Diabético depende do empenho, comunicação e treinamento da equipe multidisciplinar para a redução das amputações e morbimortalidade dos diabéticos

O papel do enfermeiro na prevenção das lesões na síndrome do pé diabético

The aim was to identify the role of nurses in preventive care for Diabetic Foot injuries. Descriptive-exploratory study, of a quantitative nature. Carried out in a health clinic located in the city of São Paulo, with 65 diabetic patients, between 18 and 90 years old. Among the study participants, the highest percentage of those who showed signs and symptoms of Diabetic Foot Syndrome were among those who had the diagnosis a longer time ago, had greater resistance to changes in habits and adherence to treatment, did not follow the guidelines on foot care and/or had other associated chronic diseases. The nurse is fundamental in early diagnosis, interventions and education on preventive care. The prevention of Diabetic Foot complications depends on the commitment, communication and training of the multidisciplinary team to reduce amputations and morbidity and mortality of diabetics.Objetivou-se identificar o papel do enfermeiro nos cuidados preventivos das lesões do Pé Diabético. Estudo descritivo-exploratório, de natureza quantitativa. Realizado em uma clínica de saúde localizada no município de São Paulo, com 65 pacientes diabéticos, entre 18 e 90 anos. Entre os participantes do estudo, a maior porcentagem dos que apresentavam sinais e sintomas da Síndrome do Pé Diabético, estavam entre os que tiveram o diagnóstico há mais tempo, possuíam maior resistência a mudanças de hábito e adesão ao tratamento, não seguiam as orientações sobre os cuidados com os pés e/ou possuíam outras doenças crônicas associadas. O enfermeiro é fundamental no diagnóstico precoce, intervenções e educação sobre cuidados preventivos. A prevenção das complicações do Pé Diabético depende do empenho, comunicação e treinamento da equipe multidisciplinar para a redução das amputações e morbimortalidade dos diabéticos