Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency. Methods: At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output. Results: Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19. Discussion: Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.

Association between ANGPTL-4 and the proinflammatory process in cancer cachexia patients.

BACKGROUND: Contradictory results are reported for the role of angiopoietin-like 4 (ANGPTL-4) in the development of cancer-cachexia and inflammation, given its importance in angiogenesis and inflammatory signaling. Our aim was to analyze the levels of ANGPTL-4 in colorectal cancer patients with a stable weight and those with cachexia in order to establish a relationship between ANGPTL-4 and the inflammatory process. RESULTS: Plasma and tumor levels of ANGPTL-4 were higher in CC in comparison to other groups. A positive association was verified between plasmatic ANGPTL-4 and NFκB levels in tumor from CC. In WSC, we identified an association between the plasmatic ANGPTL-4, IL-15, and IL-10 in tumor and IL-15 in MES. Increased levels of NFκB and TNF-R1 in MES were detected in CC in comparison to WSC. Specifically in CC-group, a positive correlation was found between ANGPTL-4 levels and those of IL-1ß, TNF-α, and NFκB in tumor, along with an association between ANGPTL-4 levels with IL-1ß and MCP-1 levels in tumor; and ANGPTL-4 and IL-1ß levels in MES. METHODS: We studied 102 patients, who were divided into three groups: control patients (C, n=37), cancer patients with a stable weight (WSC, n=23), and cancer-cachexia patients (CC, n=42). Samples of plasma, tumor, mesenteric (MES) and subcutaneous adipose tissue were removed for the determination of ANGPTL-4 levels and other proinflammatory factors. CONCLUSIONS: ANGPTL-4 levels were higher in plasma and tumor of CC-group, and positively associated with pro-inflammatory and pro-tumorigenic factors. Our results suggest an opposite effect of ANGPTL-4 depending on the concentration and presence of cachexia.

Liver lipid metabolism disruption in cancer cachexia is aggravated by cla supplementation -induced inflammation.

BACKGROUND & AIMS: The liver is the main organ regulating metabolism. In spite of that, few studies examine liver metabolism in cachexia, a wasting syndrome associated with increased morbidity and mortality in cancer. Cachexia induces major metabolic disruption, inflammation and fat and lean mass loss. We have previously shown impairment of hepatic lipid metabolism in cancer cachexia that contributes to the aggravation of the symptoms. The present study addresses the effects of Conjugated Linoleic Acid supplementation upon liver lipid metabolism in cachectic rats. METHODS: Male Wistar rats were randomly assigned to control groups (C) receiving 0.9 NaCl (Placebo CP); or to groups supplemented with sunflower oil (CSF), supplemented with CLA (CCLA), or still, to tumour bearing animals (T) receiving NaCl (TP), sunflower oil (TSF), or CLA (TCLA). Supplementation (0.5 ml) by gavage was carried out for 14 days. Body weight, dietary intake, glucose, cholesterol and triacylglycerol plasma content, liver glycogen and triacylglycerol content and mRNA expression of liver carnitine palmitoyltransferase I and II (CPT I and II), as well as microsomal triglyceride transfer protein (MTP), liver fatty acid-binding protein (L-FABP), peroxisome proliferator-activated receptor-alpha (PPAR-alpha), and apolipoprotein B (apoB), were assessed. RESULTS: Liver CPT II activity was reduced in all groups, when compared with CP. Hepatic mRNA expression of MTP, apoB and FABP was reduced in TCLA, when compared with all groups. TCLA also presented increased hepatic and plasma triacylglycerol content, when compared with all T groups. Adipose tissue-derived inflammatory factors were assessed. No differences among the groups were observed in regard to Retro Peritoneal Adipose Tissue cytokine (IL-1ß, IL-6, and TNF-α) protein content and expression, with the exception of IL-10 in tumour-bearing animals. In the Epididymal Adipose Tissue, the inflammatory cytokines were augmented in TCLA, compared with all other groups. CONCLUSION: CLA supplementation fails to promote the re-establishment of hepatic lipid metabolism in tumour-bearing animals, and therefore is not recommended in cancer-related cachexia.

Physical exercise contributes to cisplatin-induced nephrotoxicity protection with decreased CD4+ T cells activation.

Cisplatin is a chemotherapy used to treat different types of cancer, such as testicular, bladder and head and neck. Physical exercise has been shown to improve cancer therapy and recently, it was demonstrated to be able to diminish side effects such as acute kidney injury (AKI), a common side effect in cisplatin treatment. In both cases, the modulation of inflammatory cytokines seems to be one of the mechanisms, but little is known about the immune cells in this process. Here, we investigated the role of CD4 + T cells in the AKI protection by physical exercise. We subjected C57Bl6 mice to long-term physical exercise (EX) before cisplatin treatment. Sedentary groups were used as control (CT). We confirmed that physical exercise decreased AKI by evaluating creatinine and Kim-1 levels, in the serum and kidney respectively. Analyzing the organs weight, we noticed a decrease in sedentary (CIS) and exercised (CIS-EX) cisplatin treated groups. Epididymal and brown adipose tissue weight were decreased in cisplatin treated subjects in comparison to untreated groups, as well as liver and spleen. We then investigated the profile of CD4 + T cells in the spleen and we observed increased levels of Tregs and CD4+CD25+ cells in CIS group, while CIS-EX presented similar amounts as control groups. Analyzing the kidney lymph nodes, we noticed a decrease of CD4+ cells in both CIS and CIS-EX group. However, a more activated phenotype (CD69+ and CD25+) was observed in CIS groups in comparison to CIS-EX group, as well as the presence of Tregs. We then investigated the production of cytokines by these cells and no difference among the groups was observed in cytokines production in splenic CD4 + T cells. However, a clear increase in TNF and IL-10 production was observed in CD4 + T cells from lymph nodes, while CIS-EX group presented similar levels as the control groups. We confirmed that physical exercise was able to diminish cisplatin-induced AKI with concomitant decrease in CD4 + T cell activation.

Cytometric evaluation of abdominal subcutaneous adipocytes after percutaneous CO2 infiltration.

OBJECTIVE: To evaluate the effects of carbon dioxide infusion to abdominal wall adipocytes. METHODS: Fifteen volunteers were subjected to sessions of CO2 infusion for three consecutive weeks (two sessions per week with intervals of two to three days between each). The volume of carbon dioxide infused per session, at points previously marked, was always calculated on the basis of surface area to be treated, with a fixed infused volume of 250 ml/100 cm² of treated surface. The infiltration points were marked respecting the limit of 2 cm equidistant between them. At each point 10 ml was injected per session, with a flow of 80 ml/min. Fragments were collected from subcutaneous tissue of the anterior abdominal wall before and after treatment. The number and histomorphological changes of adipocytes (mean diameter, perimeter, length, width and number of adipocytes per field of observation) were measured by computerized cytometry. The results were analyzed with paired Student t test, adopting a significance level of 5% (p <0.05). RESULTS: There was a significant reduction in the number of adipocytes in the abdominal wall, as well as the area, diameter, perimeter, length and width of the adipocytes, after the infusion of CO2 (p = 0.0001). CONCLUSION: The percutaneous infiltration of CO2 reduces the population of adipocytes of the anterior abdominal wall and modifies their morphology.

Avaliação citométrica dos adipócitos localizados no tecido subcutâneo da parede anterior do abdome após infiltração percutânea de CO2 / Cytometric evaluation of abdominal subcutaneous adipocytes after percutaneous CO2 infiltration

OBJETIVO: Avaliar os efeitos da infiltração de dióxido de carbono em adipócitos presentes na parede abdominal. MÉTODOS: Quinze voluntárias foram submetidas a sessões de infusão de CO2 durante três semanas consecutivas (duas sessões por semana com intervalos de dois a três dias entre cada sessão). O volume de gás carbônico infundido por sessão, em pontos previamente demarcados, foi sempre calculado com base na superfície da área a ser tratada, com volume infundido fixo de 250 mL/100cm² de superfície tratada. Os pontos de infiltração foram demarcados respeitando-se o limite eqüidistante 2cm entre eles. Em cada ponto se injetou 10mL, por sessão, com fluxo de 80mL/min. Foram colhidos fragmentos de tecido celular subcutâneo da parede abdominal anterior antes e após o tratamento. O número e as alterações histomorfológicas dos adipócitos (diâmetro médio, perímetro, comprimento, largura e número de adipócitos por campos de observação) foram mensurados por citometria computadorizada. Os resultados foram analisados com o teste t de Student pareado, adotando-se nível de significância de 5 por cento (p<0,05). RESULTADOS: Encontrou-se redução significativa no número de adipócitos da parede abdominal e na área, diâmetro, perímetro, comprimento e largura após o uso da hipercapnia (p=0,0001). CONCLUSÃO: A infiltração percutânea de CO2 reduz a população e modifica a morfologia dos adipócitos presentes na parede abdominal anterior.

OBJECTIVE: To evaluate the effects of carbon dioxide infusion to abdominal wall adipocytes. METHODS: Fifteen volunteers were subjected to sessions of CO2 infusion for three consecutive weeks (two sessions per week with intervals of two to three days between each). The volume of carbon dioxide infused per session, at points previously marked, was always calculated on the basis of surface area to be treated, with a fixed infused volume of 250 ml/100cm² of treated surface. The infiltration points were marked respecting the limit of 2cm equidistant between them. At each point 10 ml was injected per session, with a flow of 80ml/min. Fragments were collected from subcutaneous tissue of the anterior abdominal wall before and after treatment. The number and histomorphological changes of adipocytes (mean diameter, perimeter, length, width and number of adipocytes per field of observation) were measured by computerized cytometry. The results were analyzed with paired Student t test, adopting a significance level of 5 percent (p <0.05). RESULTS: There was a significant reduction in the number of adipocytes in the abdominal wall, as well as the area, diameter, perimeter, length and width of the adipocytes, after the infusion of CO2 (p = 0.0001). CONCLUSION: The percutaneous infiltration of CO2 reduces the population of adipocytes of the anterior abdominal wall and modifies their morphology.

Impacto da desidratação na geração de força de atletas de arco e flecha durante competição Indoor e Outdoor / Impact of dehydration in the strength generation of archery athletes during Indoor and Outdoor competition

INTRODUÇÃO: O arco e flecha é um esporte estático que requer força e resistência da parte superior do corpo, sendo que a habilidade do arqueiro é definida pela capacidade de atirar a flecha no alvo em um intervalo de tempo com precisão. A contração muscular gerada durante a execução do gesto esportivo propicia o aumento da temperatura corporal, da oxidação de glicose e da sudorese, podendo esta ser potencializada pelas condições climáticas às quais o atleta é exposto. Todos estes fatores alteram a percepção de esforço e a própria geração de força, impondo um estresse negativo à performance. OBJETIVOS: Avaliar e relacionar o estado de hidratação de atletas de arco e flecha com alterações fisiológicas e de força intervenientes no rendimento competitivo. MÉTODOS: Participaram 11 arqueiros em duas competições distintas (indoor e outdoor). Foram mensurados parâmetros relacionados ao estado de hidratação, glicemia, percepção de esforço subjetivo e alteração na força de preensão palmar. RESULTADOS: Os atletas analisados apresentaram alterações significativas nos parâmetros relacionados ao estado hídrico em diferentes dias, provavelmente relacionadas às condições climáticas adversas na competição outdoor (34ºC e 60 por cento URA) em relação à competição indoor (22ºC e 90 por cento URA). O mesmo não foi observado para a glicemia. CONCLUSÃO: Este trabalho é o primeiro a comprovar a relação direta entre fatores climáticos e de rendimento em arqueiros de alto nível durante evento competitivo, assim como a evidenciar quais métodos não invasivos seriam os mais indicados para a avaliação do impacto destas alterações.

INTRODUCTION: Archery is a static sport that requires strength and resistance from the upper part of the body, and the skill of the archer is defined by the capacity to shoot the arrow on the target in an interval of time with accuracy. The muscle contraction generated during the performance of the sports gesture causes the increase in body temperature, glucose oxidation and the sweat loss, being able to be boosted by the climate conditions to which the athlete is exposed. These factors combined modify the effort perception and the proper strength generation, imposing hence stress negative to performance. OBJECTIVE: To evaluate and to relate the hydration status of archery athletes to intervening physiological and strength alterations in the competitive performance. METHODS: 11 archers participated in two distinct competitions (indoor and outdoor). Parameters related to the hydration status, glycemia, subjective perceived exertion and alteration in handgrip were measured. RESULTS: The analyzed athletes presented significant alterations in the parameters related to their hydration on different days, probably related to the adverse weather conditions in the outdoor events(34ºC and 60 percent). The same situation was not observed for glycemia. CONCLUSION: This investigation is a pioneer in proving the straight relation between weather conditions and performance in high-level archers during competitive events, as well as evidencing which non-invasive methods would be recommended to assessment of the impact of these alterations.

Efeito anti-inflamatório do treinamento físico na insuficiência cardíaca: papel do TNF-α e da IL-10: [revisão] / Anti-inflammatory effect of physical training in heart failure: role of TNF-α and IL-10: [review] / Efecto antiinflamatorio del entrenamiento físico en la insuficiencia cardiaca: rol del TNF-α y de la IL-10: [revisión]

Nos últimos 50 anos, a compreensão sobre as alterações deteriorativas envolvidas na progressão da insuficiência cardíaca (IC), descritas inicialmente como decorrentes de alterações na retenção de sais e fluidos, ou alterações nos parâmetros hemodinâmicos, mudou significatiamente. Recentemente, diversos estudos em pacientes com IC demonstraram níveis plasmáticos (ou no soro) alterados de citocinas pro-inflamatórias, tais como o fator α de necrose tumoral (TNF-α), as interleucinas 1, 6 e 18, e a cardiotropina-1, dentre outros marcadores inflamatórios. Essas alterações monstraram-se independentes da etiologia da IC, sugerindo uma via patogênica comum. Em reposta a esses novos achados, intervenções no sentido de evitar e/ou reduzir essas alterações inflamatória tem sido propostas. Os benefícios cardiovasculares, induzidos treinamento aeróbio realizados em intensidades variando de leve a moderada, têm sido previamente relatados. Além disso, tem-se demonstrado que o treinamento físico (aeróbio moderado) parece capaz de modular, na vigência de um quadro inflamatório crônico anormal, a expressão elevada de citocinas pró-inflamatórias, moléculas de adesão solúveis, fatores quimioatratantes e estresse oxidativo. Tomados em conjunto, esses dados indicam um possível efeito anti-inflamatório induzido pelo treinamento físico. Dessa forma, esta revisão tem por objetivo abordar o treinamento físico como uma alternativa não farmacológica adjuvante a ser administrada em alguns quadros patológicos em que predominam as alterações crônicas do TNF-α, como na IC. Por sua vez, o "efeito anti-inflamatório" induzido pelo treinamento físico parece ser mediado principalmente pela IL-10.

Over the past 50 years, the understanding of the deteriorative changes involved in the progression of heart failure (HF), initially described as resulting from changes in salt and fluid retention, or changes in hemodynamic parameters, have changed significantly. Recently, several studies conducted in HF patients showed altered plasma (or serum) levels of pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukins 1, 6, and 18, and cardiotropin-1, among other inflammatory markers. These changes were independent of HF etiology, suggesting a common pathogenic pathway. In response to these new findings, interventions to prevent and/or reduce these inflammatory changes have been proposed. The aerobic training-induced cardiovascular benefits of physical exercises performed at intensities ranging from mild to moderate have been previously reported. Moreover, it has been shown that moderate aerobic physical training seems to be able to modulate, in the presence of an abnormal chronic inflammatory condition, the overexpression of pro-inflammatory cytokines, soluble adhesion molecules, chemoattractant factors and oxidative stress. Altogether, these data indicate a possible anti-inflammatory effect induced by physical training. Therefore, this review aims to assess the role of physical training as an alternative non-pharmacological adjuvant to be administered in some pathological conditions in which TNF-α chronic changes are predominant, as in HF. The "anti-inflammatory effect" induced by physical training seems to be primarily mediated by IL-10.

En los últimos 50 años, la comprensión sobre las alteraciones deteriorativas involucradas en la progresión de la insuficiencia cardiaca (IC), descriptas inicialmente como causadas por alteraciones en la retención de sales y fluidos, o alteraciones en los parámetros hemodinámicos, ha cambiado significativamente. Recientemente, diversos estudios en pacientes con IC han demostrado niveles plasmáticos (o en el suero) alterados de citosinas proinflamatorias, tales como el factor α de necrosis tumoral (TNF-α), las interleuquinas 1, 6 y 18, y la cardiotropina-1, entre otros marcadores inflamatorios. Esas alteraciones se mostraron independientes de la etiología de la IC, sugiriendo una vía patogénica común. En respuesta a esos nuevos hallazgos, se vienen proponiendo intervenciones en el sentido de evitar y/o reducir esas alteraciones inflamatorias. Se viene relatando previamente los beneficios cardiovasculares, inducidos por el entrenamiento aerobio realizado en intensidad variando de ligera a moderada. Además, se está demostrando que el entrenamiento físico (aerobio moderado) parece capaz de modular, en la vigencia de un cuadro inflamatorio crónico anormal, la expresión elevada de citosinas proinflamatorias, moléculas de adhesión solubles, factores quimioatractantes y estrés oxidactivo. Tomados en conjunto, esos datos indican un posible efecto Antiinflamatorio inducido por el entrenamiento físico. Así, esta revisión tiene por objeto abordar el entrenamiento físico como una alternativa no farmacológica adyuvante que se administrará en algunos cuadros patológicos donde predominan las alteraciones crónicas del TNF-α, como en la IC. A su vez, el "efecto antiinflamatorio" que el entrenamiento físico induce parece mediarse sobre todo por la IL-10.

Anti-inflammatory effect of physical training in heart failure: role of TNF-alpha and IL-10.

Over the past 50 years, the understanding of the deteriorative changes involved in the progression of heart failure (HF), initially described as resulting from changes in salt and fluid retention, or changes in hemodynamic parameters, have changed significantly. Recently, several studies conducted in HF patients showed altered plasma (or serum) levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukins 1, 6, and 18, and cardiotropin-1, among other inflammatory markers. These changes were independent of HF etiology, suggesting a common pathogenic pathway. In response to these new findings, interventions to prevent and/or reduce these inflammatory changes have been proposed. The aerobic training-induced cardiovascular benefits of physical exercises performed at intensities ranging from mild to moderate have been previously reported. Moreover, it has been shown that moderate aerobic physical training seems to be able to modulate, in the presence of an abnormal chronic inflammatory condition, the overexpression of pro-inflammatory cytokines, soluble adhesion molecules, chemoattractant factors and oxidative stress. Altogether, these data indicate a possible anti-inflammatory effect induced by physical training. Therefore, this review aims to assess the role of physical training as an alternative non-pharmacological adjuvant to be administered in some pathological conditions in which TNF-alpha chronic changes are predominant, as in HF. The 'anti-inflammatory effect' induced by physical training seems to be primarily mediated by IL-10.

Hepatic denervation impairs the assembly and secretion of VLDL-TAG.

VLDL secretion is a regulated process that depends on the availability of lipids, apoB and MTP. Our aim was to investigate the effect of liver denervation upon the secretion of VLDL and the expression of proteins involved in this process. Denervation was achieved by applying a 85% phenol solution onto the portal tract, while control animals were treated with 9% NaCl. VLDL secretion was evaluated by the Tyloxapol method. The hepatic concentration of TAG and cholesterol, and the plasma concentration of TAG, cholesterol, VLDL-TAG, VLDL-cholesterol and HDL-cholesterol were measured, as well as mRNA expression of proteins involved in the process of VLDL assembly. Hepatic acinar distribution of MTP and apoB was evaluated by immunohistochemistry. Denervation increased plasma concentration of cholesterol (125.3 +/- 10.1 vs. 67.1 +/- 4.9 mg dL(-1)) and VLDL-cholesterol (61.6 +/- 5.6 vs. 29.4 +/- 3.3 mg dL(-1)), but HDL-cholesterol was unchanged (45.5 +/- 6.1 vs. 36.9 +/- 3.9 mg dL(-1)). Secretion of VLDL-TAG (47.5 +/- 23.8 vs. 148.5 +/- 27.4 mg dL h(-1)) and mRNA expression of CPT I and apoB were reduced (p < 0.01) in the denervated animals. MTP and apoB acinar distribution was not altered in the denervated animals, but the intensity of the reaction was reduced in relation to controls.

Efeito da temporada de basquetebol profissional sobre o perfil lipídico / Effect of the professional basketball season on the lipids profile

O objetivo do presente estudo foi verificar o efeito da temporada de basquetebol profissional sobre o perfil lipídico. Sete jogadores profissionais (idade: 23,6 mais ou menos 4,3 anos; massa corporal: 110,2 mais ou menos 17,5 kg; estatura: 195,4 mais ou menos 10,3 cm) foram avaliados antes e após um período de 4 meses, relativos a uma temporada nacional de basquetebol profissional (2 partidas por semana, 2 a 3 sessões de treinos técnicos e tático, 2 a 3 sessões de treino de musculação, 1 a 2 sessões de treino regenerativo e 1 dia de descanso passivo, sendo todos a média por semana) . Os jogadores foram submetidos a análise antropométrica e coleta sanguínea. A primeira visita foi feita antes do início da temporada e a segunda visita dois dias (48 horas) após o término da última partida da temporada. Foram realizadas análises do perfil lipídico (TAG - Triacilglicerol, VLDL - Very low density lipoprotein, LDL-c – Low density lipoprotein cholesterol, HDL-c –high density lipoprotein cholesterol, e colesterol total) por kits comerciais (Labtest®, Brasil). A comparação entre os resultados foi realizada pareadamente (antes e depois o início da temporada) por teste não paramétrico de Wilcoxon. Utilizou-se o nível de significância de 5% (p menor que 0,05). Após a temporada, foi demonstrada diminuição nas concentrações da LDL-c (pré: 111,40 mais ou menos 9 mg/dL vs pós: 84,60 mais ou menos 8,50 mg/dL; p menor que 0,05), bem como do colesterol total (pré: 171,20 mais ou menos 6,44 mg/dL vs pós: 148,20 mais ou menos 6,37 mg/dL; p menor que 0,05). Além disso, foi encontrado aumento na taxa HDL/colesterol total (pré: 0,22 mais ou menos 0,03 vs pós: 0,27 mais ou menos 0,06; p menor que 0,05)...

The aim of the present study was to verify the effect of the professional basketball season on the lipids profile. Seven professional players (age: 23.6 more or less 4.3 years; body mass: 110.2 more or less 17.5 kg; height: 195.4 more or less 10.3 cm) were evaluated before and after a period ranging 4 moths, during national professional basketball season (2 games per week, 2 to 3 tactical and technical exercise workout, 2 to 3 strength exercise workout, 1 to 2 recuperative workout and 1 day of passive rest, all of then as a median per week). Blood samples and anthropometric measures were taken. The first visit was made before the beginning of the season and the second visit two days (48 hours) after the ending of the last game of the season. The lipids profile (TG - Triglyceride, VLDL - very low density lipoprotein, LDL-c – Low density lipoprotein cholesterol, HDL-c – High density lipoprotein cholesterol, and total cholesterol) was analyses by commercial kits (Labtest®, Brazil). The comparison between the results (before and after) was carried through by non parametric Wilcoxon pair test. The level of significance of 5% was used (p smaller that 0.05). After basketball season, a reduction in the LDL-c plasma concentrations was demonstrated (before: 111.40 more or less 9 mg/dL after: 84.60 more or less 8.50mg/dL; p smaller that 0.05), as well as in total cholesterol (before: 171.20 more or less 6.44 mg/dL after: 148.20 more or less 6.37 mg/dL; p smaller that 0.05). Besides, increase in rate the HDL/total cholesterol was found (before: 0.22 more or less 0.03 after: 0.27 more or less 0.06; p smaller that 0.05). The results herein found indicate that the basketball season may induce changes in LDL-c, total cholesterol and in rate the HDL/total cholesterol concentrations, suggesting a modulatory effect on the lipid profile in professional basketball player after 4 moths season.

Influência do treinamento físico aeróbio no transporte mitocondrial de ácidos graxos de cadeia longa no músculo esquelético: papel do complexo carnitina palmitoil transferase / Influence of aerobic physical training in the motochondrial transport of long chain fatty acids in the skeletal muscle: role of the carnitine palmitoil transferase

O ácido graxo (AG) é uma importante fonte de energia para o músculo esquelético. Durante o exercício sua mobilização é aumentada para suprir as necessidades da musculatura ativa. Acredita-se que diversos pontos de regulação atuem no controle da oxidação dos AG, sendo o principal a atividade do complexo carnitina palmitoil transferase (CPT), entre os quais três componentes estão envolvidos: a CPT I, a CPT II e carnitina acilcarnitina translocase. A função da CPT I durante o exercício físico é controlar a entrada de AG para o interior da mitocôndria, para posterior oxidação do AG e produção de energia. Em resposta ao treinamento físico há um aumento na atividade e expressão da CPT I no músculo esquelético. Devido sua grande importância no metabolismo de lipídios, os mecanismos que controlam sua atividade e sua expressão gênica são revisados no presente estudo. Reguladores da expressão gênica de proteínas envolvidas no metabolismo de lipídios no músculo esquelético, os receptores ativados por proliferadores de peroxissomas (PPAR) alfa e beta, são discutidos com um enfoque na resposta ao treinamento físico.

Fatty acids are an important source of energy for the skeletal muscle. During exercise, their mobilization is increased to supply the muscle energetic needs. Many points of regulation act in the fatty acids metabolism, where the carnitine palmytoiltransferase (CPT) complex is the main control system. Three compounds named CPT I, CPT II and carnitine acyl carnitine translocase (CACT) are components of this system. Its function is to control the influx of fatty acids inside the mitochondria for posterior oxidation and energy production. There is a pronounced increase in both activity and gene expression of CPT I in the skeletal muscle in response to exercise. Due to its importance in lipid metabolism, the controlling mechanisms are reviewed in the present study. The modulation of gene expression by peroxisome proliferator-activated receptors (PPARs) alpha and beta during the physical training is also discussed in this review.

Beta-hydoxy-beta-methylbutyrate supplementation affects Walker 256 tumor-bearing rats in a time-dependent manner.

BACKGROUND & AIMS: Cancer cachexia affects intermediary metabolism with intense and general catabolism. Walker 256 tumor is a model injected either subcutaneously (Sc) or intraperitoneally (Ip), with different metabolic features. Beta-hydroxy beta-methylbutyrate (HMbeta) is a leucine metabolite with anti-catabolic properties, the aim of this study being to investigate its effects on metabolic parameters in both tumor models. METHODS: Controls (subcutaneous control group (ScC) and intraperitoneal control group (IpC)) and supplemented animals (subcutaneous supplemented group (ScS) and intraperitoneal supplemented group (IpS)) showed these results. RESULTS: Protein Sc values were (47.8%) lower than Ip groups. Sc group fat content was (65.16%) higher than Ip groups. Liver glycogen value for Sc groups was (38.4%) higher than Ip groups. Muscle glycogen value for Sc groups were (2.75 times) higher than Ip groups. Corticosterone and insulin values were lower (44.53%) and higher (45.94%), respectively, in Sc when compared with Ip groups. Glucose and lactate values for ScS were the lowest (61.7% and 41.53%) compared to other groups. ScC glutamine value was the highest (40.8%) of all groups. Glutamate Sc values were (42.65%) lower than Ip groups. Sc groups showed greater survival time compared with Ip groups. ScS group showed 100% increase in survival time when compared with ScC. CONCLUSIONS: HMbeta supplementation can increase survival time and promotes metabolic changes in cancer-bearing animals, but it seems to work in a time-dependent manner.

Reduced maximal oxygen consumption and overproduction of proinflammatory cytokines in athletes.

OBJECTIVE: It was the aim of this study to evaluate whether chronic pain in athletes is related to performance, measured by the maximum oxygen consumption and production of hormones and cytokines. METHODS: Fifty-five athletes with a mean age of 31.9 +/- 4.2 years engaged in regular competition and showing no symptoms of acute inflammation, particularly fever, were studied. They were divided into 2 subgroups according to the occurrence of pain. Plasma concentrations of adrenaline, noradrenaline, cortisol, prolactin, growth hormone and dopamine were measured by radioimmunoassay, and the production of the cytokines interleukin (IL)-1, IL-2, IL-4, IL-6, tumor necrosis factor-alpha, interferon-alpha and prostaglandin E(2) by whole-blood culture. Maximal oxygen consumption was determined during an incremental treadmill test. RESULTS: There was no change in the concentration of stress hormones, but the athletes with chronic pain showed a reduction in maximum oxygen consumption (22%) and total consumption at the anaerobic threshold (25%), as well as increased cytokine production. Increases of 2.7-, 8.1-, 1.7- and 3.7-fold were observed for IL-1, IL-2, tumor necrosis factor-alpha and interferon-alpha, respectively. CONCLUSIONS: Our data show that athletes with chronic pain have enhanced production of proinflammatory cytokines and lipid mediators and reduced performance in the ergospirometric test.

Exercise restores immune cell function in energy-restricted rats.

OBJECTIVE: To evaluate the effect of chronic moderate-intensity exercise upon the alterations of immune system cell function induced by energy restriction. METHODS: Forty male Wistar rats were randomly assigned to the following groups: sedentary animals fed ad libitum (SF, N = 10) or submitted to energy restriction (SER, N = 10, receiving 50% of the mean amount of chow consumed by SF); and trained animals fed ad libitum (TF, N = 10) or submitted to energy restriction (TER, N = 10), who exercised on a treadmill (at 60-65%VO(2max) 5 d.wk(-1) for 10 wk(-1), after 30 d under the restriction protocol. The incorporation of [2-(14)C]-thymidine by lymphocytes obtained from the spleen and mesenteric lymph nodes, plasma glucose and glutamine concentration, and cytokine production by cells cultivated in the presence of glutamine were measured in all groups, 24 h after the last exercise session. Two-way ANOVA and Tukey's posttest were employed for the statistical analysis. RESULTS: Training induced an increase in the proliferative response and in the production of gamma-interferon and interleukin-1 (P < 0.05) in cells from the spleen and lymph nodes of SER, in which these parameters were diminished when compared with SF (P < 0.05). SER spleen and lymph node cells produced more TNF (26 and 42%, respectively) and IL-2 (49 and 42%, respectively) than SF. The Th1-like diversion of the immune response observed in SER persisted after training. Partial recovery of the decreased SER plasma glutamine concentration and muscle glutamine synthase mRNA was observed. CONCLUSIONS: Training induced the recovery of the proliferative capacity of lymphocytes from SER, probably due to the partial restoration of plasma glutamine levels, but did not interfere with the diversion towards a Th1-type immune response induced by food restriction.

Influência da suplementação lipídica sobre a indução do efeito poupador de glicogênio em ratos submetidos ao exercício de “endurance" / Glycogen sparing effect induced by lipid supplementation in rats submitted to endurance exercise

Diversos estudos relacionam a adoção de dietas hiperlipídicas ao aumento na capacidade de utilização de lipídios e, por conseguinte, à ocorrência do efeito poupador de glicogênio. Além da maior oferta, a qualidade do lipídio oferecido é capaz de alterar sua taxa de oxidação. O objetivo deste estudo foi verificar o efeito da suplementação lipídica com diferentes tipos de óleos sobre a ocorrência do efeito poupador de glicogênio em ratos submetidos ao exercício de “endurance” (60 VO2 pico por 60 minutos). Os animais foram divididos em três grupos: grupo controle treinado (CT), grupo treinado suplementado com óleo de fígado de bacalhau (OFBT) e grupo treinado suplementado com óleo de palmiste (OPT). Após o exercício, o conteúdo de glicogênio muscular não diferiu significativamente entre todos os grupos (Gastrocnêmio - CT - 0,31 ± 0,02, OFBT - 0,25 ± 0,02, OPT - 0,26 ± 0,02; Sóleo - CT - 0,44 ± 0,04, OFBT - 0,39 ± 0,03, OPT - 0,38 ± 0,04 mg.100 mg-1 de tecido úmido). O contrário foi observado no estoque hepático de glicogênio. Os grupos suplementados (OFBT - 1,21 ± 0,05, OPT - 1,02 ± 0,03 mg.100 mg-1 de tecido úmido)apresentaram uma redução drástica em relação ao CT (2,12 ± 0,14 mg.100 mg-1 de tecido úmido). Em ratos, conforme demonstrado anteriormente, a redução do conteúdo hepático de glicogênio e a subseqüente hipoglicemia constituem os fatores limitantes para o desempenho; portanto, independentemente do tipo de lipídio oferecido,os animais suplementados apresentaram menor estoque hepático de glicogênio e, conseqüentemente, essa adaptação será deletéria para o desempenho.

Suplementaçäo lipídica para atividades de "endurance" / Lipid supplementation in endurance activities

Os ácidos graxos säo o principal substrato energético utilizado pelas fibras musculares durante a realizaçäo de um exercício de intensidade submáxima e longa duraçäo. A instalaçäo da fadiga periférica durante este tipo de atividade está relacionada à reduçäo dos estoques endógenos de carboidrato. A adoçäo da suplementaçäo lipídica visa maximizar a utilizaçäo deste tipo de substrato em detrimento aos estoques de carboidrato, promovendo assim, o efeito poupador de glicogênio ("sparing effect"). A suplementaçäo lipídica para atividades de "endurance" pode ser classificada em duas principais estratégias: a) elevaçäo aguda dos ácidos graxos no plasma e b) administraçäo de dietas hiperlipídicas. Existe, contudo, muita controvérsia em relaçäo aos possíveis efeitos benéficos ou deletérios deste tipo de suplementaçäo para atletas. O objetivo deste trabalho foi revisar a literatura sobre os efeitos da suplementaçäo lipídica sobre o desempenho físico tento de animais como de humanos