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Purpose The purpose of this study is to evaluate the effect of Hibiscus sabdariffa ethanolic extract (HsE) on protein levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, adiponectin and leptin in adipose tissue, as well as on the lipid and glycemic profiles of high-fat/sugar diet-induced obese (DIO) rats. Design/methodology/approach Obesity was induced in male Wistar rats through a high-fat/sugar diet provided for eight weeks. Control rats received a standard diet. The high-fat/sugar DIO animals were subsequently randomized into DIO (n = 8) and DIO treated with HsE (DIO + HsE, n = 8, 150 mg/kg/day) by gavage, for additional eight weeks. Oral glucose tolerance test was performed, and blood samples and epididymal adipose tissue were collected for biochemical analysis and adipokine protein level evaluation, respectively. Findings Compared to the DIO rats, HsE treatment decreased weight gain (50.6%) and mesenteric fat (42%), indicated as diminished visceral fat (22.5%). HsE did not affect the lipid profile and TNF-α levels in adipose tissue; however, it effectively prevented a 13% increase in fasting glucose levels and improved glucose tolerance. Compared with the C group, HsE normalized the adiponectin levels and leptin/adiponectin ratio and decreased the IL-6 (55%) and leptin (18.6%) levels in adipose tissue of obese rats. Originality/value HsE improves adipokine protein levels in high-fat/sugar DIO rats, demonstrating the clinical efficacy of HsE in the treatment of obesity and obesity-related diseases.

Hypertension is a chronic disease considered an important risk factor to high level of morbidity and mortality in the world. The objective was to evaluate the prevalence of hypertension and cardiovascular risk factors in Sinop (MT/Brazil). This cross-sectional study was conducted in 2014 between February and November. Data collection included self-reported behavioral risk factors and clinical measurements comprising blood pressure and anthropometry, totaling 649 adult subjects. The prevalence of hypertension was 39%, being higher in men (23%) than women (16%). Overall, 33.4% were obese and 39.9% were overweight; 12.5% smoke one or more packs of cigarettes per day; 68.9% were sedentary; 50.5% demonstrated altered waist/hip ratio; 22.8% and 50.8%, respectively, presented high and very high cardiovascular risk by waist circumference measure. Odds ratio analyses demonstrated that hypertension was associated with male subjects, increased age, excess weight and high waist/hip ratio as well altered waist circumference. This study showed high prevalence of hypertension, overweight and obesity in Sinop/MT. In addition, many hypertensive patients under anti-hypertensive treatment showed uncontrolled blood pressure levels. There was a significant association between hypertension and age, gender, body mass index, waist circumference and waist/hip ratio.

Made available in DSpace on 2021-06-25T15:02:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 Mato Grosso Research Foundation (FAPEMAT), Brazil Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Background. Decreased cardiac contractility has been observed in cirrhosis, but the mechanisms that initiate and maintain cardiac dysfunction are not entirely understood. Aim of the study. We test the hypothesis that cirrhotic cardiomyopathy is related to deterioration of myocardial contractility due to alterations in calcium-handling proteins expression. In addition, we evaluated whether cardiac pro-inflammatory cytokine levels are associated with this process. Methods. Cirrhosis was induced by thioacetamide (TAA, 100 mg/kg/i.p., twice weekly for eight weeks). The myocardial performance was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic challenge. The cardiac calcium handling protein expression was detected by Western blotting. Cardiac TNF-alpha and IL-6 levels were measured by ELISA. Results. Thioacetamide induced liver cirrhosis, which was associated with cirrhotic cardiomyopathy characterized by in vivo left ventricular diastolic and systolic dysfunction as well as cardiac hypertrophy. In vitro baseline myocardial contractility was lower in cirrhosis. Also, myocardial responsiveness to post-rest contraction stimulus was declined. Protein expression for RYR2, SERCA2, NCX, pPBL Ser16 and L-type calcium channel was quantitatively unchanged; however, pPBL Thr17 was significantly lower while IL-6 was higher. Conclusions. Our study demonstrates that cirrhotic cardiomyopathy is associated with decreased cardiac contractility with alteration of phospholamban phosphorylation in association with higher cardiac pro-inflammatory IL-6 levels. These findings provided molecular and functional insights about the effects of liver cirrhosis on cardiac function. (C) 2020 IMSS. Published by Elsevier Inc. Fed Univ Mato Grosso UFMT, Inst Hlth Sci, Ave Alexandre Ferronato 1200, BR-78556267 Sinop, Mato Grosso, Brazil Sao Paulo State Univ, Botucatu Sch Med, Dept Internal Med, Botucatu, SP, Brazil Sao Paulo State Univ, Botucatu Sch Med, Dept Pathol, Botucatu, SP, Brazil Sao Paulo State Univ, Botucatu Sch Med, Dept Internal Med, Botucatu, SP, Brazil Sao Paulo State Univ, Botucatu Sch Med, Dept Pathol, Botucatu, SP, Brazil Mato Grosso Research Foundation (FAPEMAT), Brazil: 161294/2014 CNPq: 442979/2014-2

Digoxin is a cardiotonic that increases the cardiac output without causing deleterious effects on heart, as well as improves the left ventricular performance during physical exercise. We tested whether the association between chronic digoxin administration and aerobic interval training (AIT) promotes beneficial cardiovascular adaptations by improving the myocardial contractility and calcium (Ca2+) handling. Male Wistar rats were randomly assigned to sedentary control (C), interval training (T), sedentary digoxin (DIGO) and T associated to digoxin (TDIGO). AIT was performed on a treadmill (1h/day, 5 days/week) for 60 days, consisting of successive 8-min periods at 80% and 20% of VO2máx for 2 min. Digoxin was administered by orogastric gavage for 60 days. Left ventricle samples were collected to analysis of Ca2+ handling proteins; contractility and Ca2+ handling were performed on isolated cardiomyocytes. TDIGO group had a greater elevation in fractional shortening (44%) than DIGO, suggesting a cardiomyocyte contractile improvement. In addition, T or TDIGO groups showed no change in cardiomyocytes properties after Fura2-acetoxymethyl ester, as well as in sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban and calcineurin expressions. The main findings indicate that association of digoxin and aerobic interval training improved the cardiomyocyte contractile function, but these effects seem to be unrelated to Ca2+ handling.

Made available in DSpace on 2020-12-12T02:14:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Background/Aims: Aortic stenosis-induced chronic pressure overload leads to cardiac dysfunction and congestive heart failure. The pathophysiological mechanisms of the myocardial impairment are multifactorial and include maladaptive β-adrenergic signaling. Exercise training (ET) has been used as a non-pharmacological therapy for heart failure management. The present study tested the hypothesis that exercise training attenuates diastolic dysfunction through β-adrenergic signaling preservation. Methods: Wistar rats were submitted to ascending aortic stenosis (AS) surgery, and after 18 weeks, a moderate aerobic exercise training protocol was performed for ten weeks. Results: ET attenuated diastolic dysfunction, evaluated by echocardiogram and isolated papillary muscle (IPM) assay. Also, ET reduced features of heart failure, cross-sectional cardiomyocyte area, and exercise intolerance, assessed by treadmill exercise testing. The β2 adrenergic receptor protein expression was increased in AS rats independently of exercise. Interestingly, ET restored the protein levels of phosphorylated phospholamban at Serine 16 and preserved the β-adrenergic receptor responsiveness as visualized by the lower myocardial compliance decline and time to 50% tension development and relaxation during β-adrenergic stimulation in the IPM than untrained rats. Additionally, AS rats presented higher levels of TNFα and iNOS, which were attenuated by ET. Conclusion: Moderate ET improves exercise tolerance, reduces heart failure features, and attenuates diastolic dysfunction. In the myocardium, ET decreases the cross-sectional area of the cardiomyocyte and preserves the β-adrenergic responsiveness, which reveals that the adjustments in β-adrenergic signaling contribute to the amelioration of cardiac dysfunction by mild exercise training in aortic stenosis rats. Department of Internal Medicine Botucatu Medical School São Paulo State University Department of Biostatistics Institute of Biosciences of Botucatu São Paulo State University Department of Pathology Botucatu Medical School São Paulo State University Institute of Health Science Federal University of Mato Grosso School of Physical Education and Sport University of São Paulo Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP) Department of Internal Medicine Botucatu Medical School São Paulo State University Department of Biostatistics Institute of Biosciences of Botucatu São Paulo State University Department of Pathology Botucatu Medical School São Paulo State University Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP) CAPES: 305399/2015-2 CAPES: 442822/2014-6

Made available in DSpace on 2020-12-12T02:02:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Cirrhotic cardiomyopathy is a condition where liver cirrhosis is associated with cardiac dysfunction. Triggers and blockers of cirrhotic cardiomyopathy are poorly understood, which might compromise the prognosis of chronic liver disease patients. We tested whether exercise training would reduce liver damage induced by thioacetamide and prevent liver cirrhosis-associated cardiomyopathy. Wistar rats were divided into three groups: control, thioacetamide (TAA), or TAA plus exercise. Thioacetamide increased liver weight and serum alanine aminotransferase and aspartate aminotransferase levels. Also, TAA treatment was involved with hepatic nodule formation, fibrotic septa, inflammatory infiltration, and hepatocyte necrosis. The exercise group presented with a reduction in liver injury status. We found that liver injury was associated with disordered cardiac hypertrophy as well as diastolic and systolic dysfunction. Exercise training attenuated cirrhosis-associated cardiac remodeling and diastolic dysfunction and prevented systolic impairment. These results provided insights that exercise training can mitigate cirrhotic cardiomyopathy phenotype. [Figure not available: see fulltext.]. Department of Internal Medicine Botucatu School of Medicine São Paulo State University (UNESP), Botucatu Institute of Health Sciences Federal University of Mato Grosso (UFMT), Avenida Alexandre Ferronato, n°1200, Setor Industrial Department of Morphology Institute of Biosciences Sao Paulo State University (UNESP) Department of Internal Medicine Botucatu School of Medicine São Paulo State University (UNESP), Botucatu Department of Morphology Institute of Biosciences Sao Paulo State University (UNESP)

Cardiotonic drugs and exercise training promote cardiac inotropic effects, which may affect training-induced cardiac adaptations. This study investigated the effects of long-term administration of digoxin on heart structure and function, and physical performance of rats submitted to high-intensity interval training (HIIT). Male Wistar rats, 60 days old, were divided into control (C), digoxin (DIGO), trained (T), and trained with digoxin (TDIGO). Digoxin was administered by gavage (30 µg/kg/day) for 75 days. The HIIT program consisted of treadmill running 60 min/day (8 min at 80% of the maximum speed (MS) and 2 min at 20% of the MS), 5 days per week during 60 days. The main cardiac parameters were evaluated by echocardiograph and cardiomyocyte area was determined by histology. There were no group x time effects of digoxin, HIIT or interactions (digoxin and HIIT) on functional echocardiographic parameters (heart rate; ejection fraction) or in the maximum exercise test. There was a group x time interaction, as evidenced by observed cardiac hypertrophy in the TDIGO group evaluated by ratio of left ventricle weight to body weight (p0.002) and cardiomyocyte area (p0.000002). Long-term administration of digoxin promoted cardiac hypertrophy without affecting cardiac function and physical performance in rats submitted to HIIT.

Objetivo: Analisar o perfil farmacoterapêutico e fatores associados a saúde de idosos polimedicados atendidos em uma Unidade Básica de Saúde (UBS) e que frequentam um Centro de Convivência do Idoso (CCI) no município de Sinop - MT. Métodos: Estudo quantitativo, com 30 idosos, 15 de cada local citado. Os dados foram obtidos por aplicação de formulários específicos durante 5 meses. Os medicamentos foram classificados segundo o Anatomical Therapeutic and Chemical Classification. Os medicamentos inapropriados (MI) para idosos classificados pelo critério de Beers-Fick. Resultados: Ocorreu maior utilização de medicamentos da classe do sistema cardiovascular (SC) (38,7%) e do sistema nervoso central (SNC) (20,7%) na UBS, enquanto os do CCI utilizaram 39,7% dos medicamentos para SC e para o trato alimentar e metabolismo (TAM) (20,4%). Porém, os idosos da UBS obtiveram maior número de MI (14,4%) comparado ao CCI (12,0%), com um maior número de possíveis interações medicamentosas (IM) (95) versus (46) do CCI. Conclusão: O perfil farmacoterapêutico diferiu entre os grupos estudados, prevalecendo classes do SC, SNC e TAM. O uso de polifarmácia foi comum, com porcentual de MI de 12, 9% e 14,4%, e maior quantidade de IM moderadas. A atenção farmacêutica mostra-se crucial para melhora da farmacoterapia em idosos polimedicados.

Aims Obesity is associated with comorbidities such as diabetes and hepatic steatosis. β-Glucans have been described as effective in treating conditions including dyslipidaemia and diabetes. Thus, the objective of this study was to evaluate the effects of botryosphaeran [(1 → 3)(1 → 6)-β-D-glucan] on obesity and its comorbidities, and understand its mechanism of action. Main methods Obesity was induced in adult male Wistar rats by ingestion of a high-fat diet and water with sucrose (300 g/L) for 8 weeks. Control rats received standard diet. After six weeks, treatment commenced with botryosphaeran (12 mg/kg.b.w., via gavage, 15 days), respective controls received water. Rats were divided into 3 groups: control (C), obese (O), and obese + botryosphaeran (OB). In the 8th week, obesity was characterized. Feed-intake, glucose and lipid profiles, glucose tolerance, and concentrations of glycogen and lipids in liver were analyzed. Protein expression was determined by Western blotting. Key findings Obese rats showed significant increases in weight gain and adipose tissue, presented glucose intolerance, dyslipidaemia, and hepatic steatosis. Botryosphaeran significantly reduced feed intake, weight gain, periepididymal and mesenteric fat, and improved glucose tolerance. Botryosphaeran also reduced triglyceride and VLDL, and increased HDL levels. Furthermore, botryosphaeran increased glycogen and reduced total lipids, triglycerides and cholesterol in liver, and increased AMP-activated protein kinase(AMPK) activity and Forkhead transcription factor 3a(FOXO3a) protein expression in adipose tissue. Significance This study demonstrated that botryosphaeran was effective in reducing obesity, hepatic steatosis, dyslipidaemia insulin resistance and glucose intolerance in diet-induced obese rats, and these effects were, at least in part, associated with reduced feed intake, and AMPK and FOXO3a activities.

Liver cirrhosis is associated with a wide range of cardiovascular abnormalities including hyperdynamic circulation and cirrhotic cardiomyopathy. The pathogenic mechanisms of these cardiovascular changes are multifactorial and include vascular dysregulations. Aim The present study tested the hypothesis that the systemic vascular hyporesponsiveness in thioacetamide (TAA)-induced liver injury model is dependent on nitric oxide (NO) and cyclooxygenase (COX) derivatives. Main methods Wistar rats were treated with TAA for eight weeks to induce liver injury. Key findings The maximal contractile response in concentration-effect curves to phenylephrine was decreased in aorta from TAA-treated rats, but no differences were found in aorta without endothelium, suggesting an endothelium-dependent mechanism in decreased contractile response. There was no difference in the contractile response with and without L-NAME (N(ω)-nitro- l -arginine methyl ester) in rats with liver injury, showing that the TAA treatment impairs NO synthesis. Pre-incubation of the aorta with indomethacin, a COX-inhibitor, normalized the reduced contractile response to phenylephrine in arteries from TAA group. Also, COX-2 and iNOS (inducible nitric oxide syntase) protein expression was increased in aorta from TAA group compared to control group. Animals submitted to TAA treatment had a reduction in systolic blood pressure. Our findings demonstrated that liver injury induced by TAA caused a decrease in aortic contractile response by a COX-dependent mechanism but not by NO release. Also, it was demonstrated an inflammatory process in the aorta of TAA-treated rats by increased expression of COX-2 and iNOS. Significance Therefore, there is an essential contribution of COX-2 activation in extra-hepatic vascular dysfunction and inflammation present in cirrhosis induced by TAA.

Background: Different types of high-fat and/or high-energy diets have been used to induce obesity in rodents. However, few studies have reported on the effects observed at the initial stage of obesity induced by high-fat feeding on cardiac functional and structural remodelling. Objective: To characterize the initial moment of obesity and investigate both metabolic and cardiac parameters. In addition, the role of Ca2+ handling in short-term exposure to obesity was verified. Methods: Thirty-day-old male Wistar rats were randomized into two groups (n = 19 each): control (C; standard diet) and high-fat diet (HF, unsaturated high-fat diet). The initial moment of obesity was defined by weekly measurement of body weight (BW) complemented by adiposity index (AI). Cardiac remodelling was assessed by morphological, histological, echocardiographic and papillary muscle analysis. Ca2+ handling proteins were determined by Western Blot. Results: The initial moment of obesity occurred at the 3rd week. Compared with C rats, the HF rats had higher final BW (4%), body fat (20%), AI (14.5%), insulin levels (39.7%), leptin (62.4%) and low-density lipoprotein cholesterol (15.5%) but did not exhibit alterations in systolic blood pressure. Echocardiographic evaluation did not show alterations in cardiac parameters. In the HF group, muscles were observed to increase their +dT/dt (C: 52.6 ± 9.0 g/mm2/s and HF: 68.0 ± 17.0 g/mm2/s; p < 0.05). In addition, there was no changes in the cardiac expression of Ca2+ handling proteins. Conclusion: The initial moment of obesity promotes alterations to hormonal and lipid profiles without cardiac damage or changes in Ca2+ handling. Resumo Fundamentos: Diferentes tipos de dietas hiperlipídicas e/ou hipercalóricas têm sido usados para induzir obesidade em roedores. No entanto, poucos estudos relataram os efeitos da obesidade induzida por dieta hiperlipídica em sua fase inicial sobre a remodelação cardíaca funcional e estrutural. Objetivo: Caracterizar o momento inicial da obesidade e investigar parâmetros metabólicos e cardíacos. Além disso, analisar o papel do trânsito de Ca+2 em curtos períodos de exposição à obesidade. Métodos: Ratos Wistar com idade de 30 dias foram distribuídos aleatoriamente em dois grupos (n = 19 em cada grupo): controle (C, dieta padrão) e dieta hiperlipídica (HL, dieta rica em gordura insaturada). O momento inicial da obesidade foi definido por medidas semanais do peso corporal, complementadas pelo índice de adiposidade (IA). A remodelação cardíaca foi avaliada por análise morfológica, histológica, ecocardiográfica e funcional dos músculos papilares. Proteínas envolvidas no trânsito de Ca2+ foram determinadas por Western Blot. Resultados: O momento inicial da obesidade ocorreu na terceira semana. Em comparação aos ratos C, os animais HL apresentaram maior peso corporal final (4%), gordura corporal (20%), IA (14,5%), níveis de insulina (39,7%), leptina (62,4%) e lipoproteína de baixa densidade (15,5%), mas não apresentaram alterações na pressão sistólica. A avaliação ecocardiográfica não mostrou alterações nos parâmetros cardíacos. No grupo HL, observou-se um aumento no +dT/dt (C: 52,6 ± 9,0 g/mm2/s e HL: 68,0 ± 17,0 g/mm2/s; p < 0,05) muscular. Além disso, não houve alterações na expressão cardíaca de proteínas envolvidas no trânsito de Ca2+. Conclusão: O momento inicial da obesidade promove alterações nos perfis hormonais e lipídicos sem causar danos cardíacos ou mudanças no trânsito de Ca2+.

Made available in DSpace on 2018-11-26T17:42:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-10-01 Fundacao de Amparo a Pesquisa e Inovacao do Estado do Espirito Santo (FAPES), Vitoria, ES, Brazil Authors have showed that obesity implicates cardiac dysfunction associated with myocardial L-type calcium channels (LTCCs) activity impairments, as well as moderate exercise training (MET) seems to be an important therapeutic tool. We tested the hypothesis that MET promotes improvements on LTCCS activity and protein expression at obesity induced by unsaturated high-fat diets, which could represent a protective effects against development of cardiovascular damage. Male Wistar rats were randomized in control (C, n = 40), which received a standard diet and obese (Ob; n = 40), which received high-fat diet. After 20 weeks, the animals were assigned at four groups: control (C; n = 12); control submitted to exercise training (ET; n = 14); obese (Ob; n = 10); and obese submitted to exercise training (ObET; n = 11). ET (5 days/week during 12 weeks) began in the 21th week and consisted of treadmill running that was progressively increased to reach 60 min. Final body weight (FBW), body fat (BF), adiposity index (AI), comorbidities, and hormones were evaluated. Cardiac remodeling was assessed by morphological and isolated papillary muscles function. LTCCs activity was determined using specific blocker, while protein expression of LTCCs was evaluated by Western blot. Unsaturated high-fat diet promoted obesity during all experimental protocol. MET controlled obesity process by decreasing of FBW, BF, and AI. Obesity implicated to LTCCs protein expression reduction and MET was not effective to prevent this condition. ET was efficient to promote several improvements to body composition and metabolic parameters; however, it was not able to prevent or reverse the downregulation of LTCCs protein expression at obese rats. Sao Paulo State Univ, Dept Internal Med, Botucatu, SP, Brazil Univ Fed Espirito Santo, Dept Sports, Ctr Phys Educ & Sports, Vitoria, ES, Brazil Sao Paulo State Univ, Dept Morphol, Botucatu, SP, Brazil Sao Paulo State Univ, Inst Biosci, Dept Biostat, Botucatu, SP, Brazil Univ Fed Mato Grosso, Inst Hlth Sci, Sinop, Brazil Sao Paulo State Univ, Dept Internal Med, Botucatu, SP, Brazil Sao Paulo State Univ, Dept Morphol, Botucatu, SP, Brazil Sao Paulo State Univ, Inst Biosci, Dept Biostat, Botucatu, SP, Brazil Fundacao de Amparo a Pesquisa e Inovacao do Estado do Espirito Santo (FAPES), Vitoria, ES, Brazil: 67633269/15

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:41:33Z No. of bitstreams: 1 S0066-782X2013000100008.pdf: 464258 bytes, checksum: bb703f1fe28d17c64b11c5137f8a3858 (MD5) Made available in DSpace on 2013-08-22T18:41:33Z (GMT). No. of bitstreams: 1 S0066-782X2013000100008.pdf: 464258 bytes, checksum: bb703f1fe28d17c64b11c5137f8a3858 (MD5) Previous issue date: 2013-01-01 Made available in DSpace on 2013-09-30T19:28:08Z (GMT). No. of bitstreams: 2 S0066-782X2013000100008.pdf: 464258 bytes, checksum: bb703f1fe28d17c64b11c5137f8a3858 (MD5) S0066-782X2013000100008.pdf.txt: 34415 bytes, checksum: 31bc7f746f4ce2df1f204208ca97b5b2 (MD5) Previous issue date: 2013-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:07:44Z No. of bitstreams: 2 S0066-782X2013000100008.pdf: 464258 bytes, checksum: bb703f1fe28d17c64b11c5137f8a3858 (MD5) S0066-782X2013000100008.pdf.txt: 34415 bytes, checksum: 31bc7f746f4ce2df1f204208ca97b5b2 (MD5) Made available in DSpace on 2014-05-20T15:07:44Z (GMT). No. of bitstreams: 2 S0066-782X2013000100008.pdf: 464258 bytes, checksum: bb703f1fe28d17c64b11c5137f8a3858 (MD5) S0066-782X2013000100008.pdf.txt: 34415 bytes, checksum: 31bc7f746f4ce2df1f204208ca97b5b2 (MD5) Previous issue date: 2013-01-01 FUNDAMENTO: A Tolerância ao Esforço Físico (TEF) é uma medida de condicionamento cardiorrespiratório. A capacidade aeróbica é reduzida na Insuficiência Cardíaca (IC), embora não haja dados disponíveis sobre esse parâmetro em animais com disfunção ventricular e sem sinais de IC. OBJETIVO: Avaliar a TEF em ratos com disfunção ventricular diastólica isolada ou associada com disfunção sistólica induzida pela Estenose da Aorta ascendente (EAo). MÉTODOS: Ratos Wistar machos jovens (20-30 dias de idade) foram divididos em Grupo Controle (GC, n = 11) e Grupo EAo (n = 12). Os animais foram avaliados em 6 e 18 semanas após a cirurgia para EAo. O teste ergométrico foi feito até a exaustão e foram avaliadas a velocidade da esteira e a concentração de lactato [LAC] no limiar de lactato, velocidade da esteira e [LAC] na exaustão, e tempo total do teste. RESULTADOS: Dados ecocardiográficos revelaram remodelação do átrio esquerdo e hipertrofia concêntrica ventricular esquerda em 6 e 18 semanas. A fração de encurtamento endocárdico mostrou-se maior no grupo EAo do que no GC em 6 e 18 semanas. A fração de encurtamento da parede média mostrou-se maior no grupo EAo do que no GC em 6 semanas. O índice cardíaco mostrou-se semelhante no GC e no grupo EAo em 6 e 18 semanas, tendo diminuído entre 6-18 semanas em ambos os grupos. A razão entre a onda E a onda A foi maior no GC do que no grupo EAo em ambos os períodos e não se alterou em ambos os grupos entre a semana 6 e a semana 18. Os parâmetros do teste de esforço na esteira foram semelhantes nos dois grupos tanto na semana 6 quanto na semana 18. CONCLUSÃO: Embora a EAo promova a disfunção diastólica isolada ou associada à disfunção sistólica, em 6 ou 18 semanas, ela não é suficiente para alterar a tolerância ao esforço físico. BACKGROUND: Physical stress tolerance (ST) is a measurement of cardiorespiratory fitness. Aerobic capacity is reduced in heart failure (HF) although there is no data available on this parameter in animals with ventricular dysfunction and no signs of HF. OBJECTIVE: Evaluate ST in rats with ventricular diastolic dysfunction isolated or associated with systolic dysfunction induced by ascending aortic stenosis (AoS). METHODS: Young male Wistar rats (20-30 days old), divided in: control group (CG, n=11) and AoSG group, (n=12). Animals were assessed at 6 and 18 weeks after AoS surgery. Treadmill exercise test was until exhaustion and evaluated treadmill speed and lactate concentration [LAC] at lactate threshold, treadmill speed and [LAC] at exhaustion, and total testing time. RESULTS: Echocardiography data revealed remodeling of the left atrium and left ventricular concentric hypertrophy at 6 and 18 weeks. Endocardial fractional shortening was greater in AoSG than CG at 6 and 18 weeks. Midwall fractional shortening was greater in AoSG than in CG only 6 week. Cardiac index was similar in CG and AoSG at 6 and 18 weeks and decreased between from 6 to 18 weeks in both groups. The E wave to A wave ratio was greater in CG than in AoSG at both periods and did not change in both groups between week 6 and 18. Treadmill stress testing parameters were similar in both groups at 6 or 18 weeks. CONCLUSION: Although AoS promotes isolated diastolic dysfunction or associated with systolic dysfunction at 6 or 18 weeks, it is not sufficient to modify physical stress tolerance. Universidade Estadual Paulista Faculdade de Medicina IDepartamento de Clínica Médica Faculdades Integradas de Bauru Universidade Federal de Mato Grosso Instituto de Ciências da Saúde Universidade Federal do Espírito Santo (UFES) Centro de Educação Física e Desportos Departamento de Desportos Universidade Federal de São Carlos (UFSCar) Laboratório de Fisiologia do Exercício Universidade Estadual Paulista Faculdade de Medicina IDepartamento de Clínica Médica

Obesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca(2+) ) handling on cardiac dysfunction in obesity models remain unknown. L-type Ca(2+) channels and sarcoplasmic reticulum (SR) Ca(2+) -ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L-type Ca(2+) channels and SERCA2a. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable high-fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L-type Ca(2+) channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca(2+) was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L-type Ca(2+) channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L-type Ca(2+) channel activity impairment without significant changes in SERCA2a expression and function as well as L-type Ca(2+) protein levels.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:41:03Z No. of bitstreams: 1 S0066-782X2010000100011.pdf: 936209 bytes, checksum: 09f0b9177605638aab2f9a09ee85ac89 (MD5) Made available in DSpace on 2013-08-22T18:41:03Z (GMT). No. of bitstreams: 1 S0066-782X2010000100011.pdf: 936209 bytes, checksum: 09f0b9177605638aab2f9a09ee85ac89 (MD5) Previous issue date: 2010-01-01 Made available in DSpace on 2013-09-30T19:27:20Z (GMT). No. of bitstreams: 2 S0066-782X2010000100011.pdf: 936209 bytes, checksum: 09f0b9177605638aab2f9a09ee85ac89 (MD5) S0066-782X2010000100011.pdf.txt: 44353 bytes, checksum: 4759a0c018f347b7aaca0868656c2096 (MD5) Previous issue date: 2010-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:07:35Z No. of bitstreams: 2 S0066-782X2010000100011.pdf: 936209 bytes, checksum: 09f0b9177605638aab2f9a09ee85ac89 (MD5) S0066-782X2010000100011.pdf.txt: 44353 bytes, checksum: 4759a0c018f347b7aaca0868656c2096 (MD5) Made available in DSpace on 2014-05-20T15:07:35Z (GMT). No. of bitstreams: 2 S0066-782X2010000100011.pdf: 936209 bytes, checksum: 09f0b9177605638aab2f9a09ee85ac89 (MD5) S0066-782X2010000100011.pdf.txt: 44353 bytes, checksum: 4759a0c018f347b7aaca0868656c2096 (MD5) Previous issue date: 2010-01-01 FUNDAMENTO: A estenose aórtica supravalvar (EAo) é utilizada para o estudo da remodelação cardíaca (RC) por sobrecarga pressórica. Nesse modelo, não estão claramente estabelecidos o comportamento da RC desde a fase inicial, nem os melhores parâmetros para a identificação da disfunção ventricular. OBJETIVOS: 1) Caracterizar, precoce e evolutivamente, as modificações morfofuncionais durante a RC em ratos com EAo e 2) identificar o índice mais sensível para detecção do momento do aparecimento da disfunção diastólica e sistólica do ventrículo esquerdo (VE). MÉTODOS: Ratos Wistar foram divididos em dois grupos - controle (GC, n=13) e EAo (GEAo, n=24) - e estudados nas 3ª, 6ª, 12ª e 18ª semanas pós-cirurgia. Os corações foram analisados por meio de ecocardiograma (ECO). RESULTADOS: Ao final do experimento, as relações do VE, do ventrículo direito e dos átrios com o peso corporal final foram aumentadas no GEAo. O ECO mostrou que o átrio esquerdo sofreu uma remodelação significativa a partir da 6ª semana. No GEAo, a porcentagem de encurtamento endocárdico apresentou queda significativa a partir da 12ª semana e a porcentagem de encurtamento mesocárdico, na 18ª semana. A relação onda E e onda A (E/A) foi superior no GC em comparação ao GEAo em todos os momentos analisados. CONCLUSÕES: O ventrículo esquerdo dos ratos com EAo, durante o processo de remodelação, apresentou hipertrofia concêntrica, disfunção diastólica precoce e melhoria da função sistólica, com posterior deterioração do desempenho. Além disso, constatou-se que os índices ecocardiográficos mais sensíveis para a detecção da disfunção diastólica e sistólica são, respectivamente, a relação E/A e a porcentagem de encurtamento endocárdico. BACKGROUND: Supravalvar aortic stenosis (SVAS) is used to study overload-induced cardiac remodeling (CR). In this model, neither CR behavior since beginning stage nor the best parameters to identify ventricular dysfunction are clearly stated. Objective: 1) Characterizing, early and evolutively, morphological and functional modifications during CR in rats with SVAS and 2) identifying the most sensitive index for detecting the moment when the diastolic and systolic dysfunction first appeared in the left ventricle (LV). METHODS: Wistar Rats were divided into two groups - control (CG, n=13) and SVAS (SVASG, n=24) - and studied in post-surgical 3rd, 6th, 12th and 18th weeks. Hearts were analyzed by means of an echocardiogram (ECHO). RESULTS: By the end of the experiment, ratios between the LV, right ventricle and atria and the final body weight were increased in the SVASG. The ECHO showed that the left atrium underwent significant remodeling from the 6th on. The percent of endocardial shortening underwent significant drop as of the 12nd week and the percent of, as of the 18th week, in the SVASG. The ratio between E- wave and A-wave (E/A) was higher in CG compared to the SVASG in all events analyzed. CONCLUSIONS: During the remodeling process, the left ventricle of rats with SVAS presented concentric hypertrophy, early diastolic dysfunction and improvement of systolic function, with posterior performance deterioration. Besides this, the study found out the most sensitive echocardiographic indexes for detecting systolic and diastolic dysfunction are, respectively, the ratio E/A and the percent of endocardial shortening. FUNDAMENTO: La estenosis aórtica supravalvular (EAo) se utiliza para el estudio de la remodelación cardiaca (RC) por sobrecarga de presión. En este modelo, no están claramente establecidos el comportamiento del RC desde la fase inicial, ni los mejores parámetros para la identificación de la disfunción ventricular. OBJETIVO: 1) Caracterizar, precoz y evolutivamente, las modificaciones morfofuncionales durante el RC en ratones con EAo, y 2) identificar el índice más sensible para detección del momento de la aparición de la disfunción diastólica y sistólica del ventrículo izquierdo (VI). MÉTODOS: Ratones Wistar se dividieron en dos grupos - control (GC, n=13) y EAo (GEAo, n=24) - y estudiados en las 3ª, 6ª, 12ª y 18ª semanas post cirugía. Los corazones se analizaron por medio de ecocardiograma (ECO). RESULTADOS: Al final del experimento, las relaciones del VI, del ventrículo derecho y de los atrios con el peso corporal final fueron aumentadas en el GEAo. El ECO mostró que el atrio izquierdo sufrió una remodelación significativa a partir de la 6ª semana. En el GEAo, el porcentaje de acortamiento endocárdico presentó disminución significativa a partir de la 12ª semana y el porcentaje de acortamiento mesocárdico, en la 18ª semana. La relación onda E y onda A (E/A) fue superior en el GC en comparación al GEAo en todos los momentos analizados. CONCLUSIÓN: El ventrículo izquierdo de los ratones con EAo, durante el proceso de remodelación, presentó hipertrofia concéntrica, disfunción diastólica precoz y mejora de la función sistólica, con posterior deterioro del desempeño. Además de ello, se constató que los índices ecocardiográficos más sensibles para la detección de la disfunción diastólica y sistólica son, respectivamente, la relación E/A y el porcentaje de acortamiento endocárdico. UNESP Faculdade de Medicina Departamento de Clínica Médica Faculdades Integradas de Bauru UNESP Faculdade de Medicina Departamento de Clínica Médica

Although long-term food restriction (FR) has been shown to induce cardiac remodeling and dysfunction, there are few data on the effects of FR on pressure-overloaded hearts. The aim of this study was to examine the effects of FR on cardiac muscle performance during inotropic stimulation in the myocardium of spontaneously hypertensive rats (SHRs). Male 60-day-old SHRs were subjected to FR for 90 days. Food-restricted animals received 50% of the ad libitum amount of food consumed by the control group. Myocardial function was studied in isolated left ventricular papillary muscle under isometric contraction in basal condition (1.25 mmol/L extracellular Ca(2+) concentration) and after 3 inotropic maneuvers: (1) at postrest contraction of 30 seconds, (2) at extracellular Ca(2+) concentration of 5.2 mmol/L, and (3) after beta-adrenergic stimulation with 10(-6) mol/L isoproterenol. At basal condition, time from peak tension to 50% relaxation was greater in the food-restricted group (P.05). Inotropic stimulation with postrest contraction and isoproterenol promoted a significant lower increase of developed tension, maximum rate of tension development, and maximum rate of tension decline in the food-restricted compared to the control group. The elevation of extracellular Ca(2+) concentration induced a lower increase of developed tension, maximum rate of tension development, and time from peak tension to 50% relaxation in the food-restricted than in the control group. In conclusion, long-term FR promotes impairment of myocardial inotropic response to calcium and beta-adrenergic stimulation in SHRs.

Made available in DSpace on 2018-11-26T16:27:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-01-01. Added 1 bitstream(s) on 2019-10-09T18:25:51Z : No. of bitstreams: 1 S0100-879X2016000400601.pdf: 742253 bytes, checksum: 055397a43390ea7b8b7a76c894fbb158 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) In experimental studies, several parameters, such as body weight, body mass index, adiposity index, and dual-energy X-ray absorptiometry, have commonly been used to demonstrate increased adiposity and investigate the mechanisms underlying obesity and sedentary lifestyles. However, these investigations have not classified the degree of adiposity nor defined adiposity categories for rats, such as normal, overweight, and obese. The aim of the study was to characterize the degree of adiposity in rats fed a high-fat diet using cluster analysis and to create adiposity intervals in an experimental model of obesity. Thirty-day-old male Wistar rats were fed a normal (n=41) or a high-fat (n=43) diet for 15 weeks. Obesity was defined based on the adiposity index; and the degree of adiposity was evaluated using cluster analysis. Cluster analysis allowed the rats to be classified into two groups (overweight and obese). The obese group displayed significantly higher total body fat and a higher adiposity index compared with those of the overweight group. No differences in systolic blood pressure or nonesterified fatty acid, glucose, total cholesterol, or triglyceride levels were observed between the obese and overweight groups. The adiposity index of the obese group was positively correlated with final body weight, total body fat, and leptin levels. Despite the classification of sedentary rats into overweight and obese groups, it was not possible to identify differences in the comorbidities between the two groups. Univ Fed Espirito Santo, Ctr Educ Fis & Esportes, Dept Desportos, Vitoria, ES, Brazil Univ Fed Mato Grosso, Inst Ciencias Saude, Sinop, MT, Brazil Univ Estadual Paulista, Fac Med, Dept Clin Med, Botucatu, SP, Brazil Univ Estadual Paulista, Inst Biociencias, Dept Bioestat, Botucatu, SP, Brazil Univ Estadual Paulista, Fac Med, Dept Clin Med, Botucatu, SP, Brazil Univ Estadual Paulista, Inst Biociencias, Dept Bioestat, Botucatu, SP, Brazil FAPESP: 2007/53267-3 FAPESP: 2006/59485-0

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:40:44Z No. of bitstreams: 1 S0066-782X2007000300015.pdf: 223052 bytes, checksum: 688955373b8ce64ffa5086d7f4759a0b (MD5) Made available in DSpace on 2013-08-22T18:40:44Z (GMT). No. of bitstreams: 1 S0066-782X2007000300015.pdf: 223052 bytes, checksum: 688955373b8ce64ffa5086d7f4759a0b (MD5) Previous issue date: 2007-03-01 Made available in DSpace on 2013-09-30T18:17:47Z (GMT). No. of bitstreams: 2 S0066-782X2007000300015.pdf: 223052 bytes, checksum: 688955373b8ce64ffa5086d7f4759a0b (MD5) S0066-782X2007000300015.pdf.txt: 28555 bytes, checksum: 812d7e600d1069bed3ab0d41600bdf05 (MD5) Previous issue date: 2007-03-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:33:41Z No. of bitstreams: 2 S0066-782X2007000300015.pdf: 223052 bytes, checksum: 688955373b8ce64ffa5086d7f4759a0b (MD5) S0066-782X2007000300015.pdf.txt: 28555 bytes, checksum: 812d7e600d1069bed3ab0d41600bdf05 (MD5) Made available in DSpace on 2014-05-20T13:33:41Z (GMT). No. of bitstreams: 2 S0066-782X2007000300015.pdf: 223052 bytes, checksum: 688955373b8ce64ffa5086d7f4759a0b (MD5) S0066-782X2007000300015.pdf.txt: 28555 bytes, checksum: 812d7e600d1069bed3ab0d41600bdf05 (MD5) Previous issue date: 2007-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) OBJETIVOS: O estudo avaliou a influência de dietas ricas em ácidos graxos saturados (AGS) e ácidos graxos insaturados (AGI) sobre a função mecânica, a morfologia e o estresse oxidativo do miocárdio de ratos. MÉTODOS: Ratos Wistar com 60 dias de idade foram alimentados com dieta padrão (n = 8) ou dietas ricas em AGS (n = 8) ou AGI (n = 8) durante 60 dias. A função mecânica foi avaliada em músculo papilar isolado do ventrículo esquerdo (VE) por meio de contrações isométrica e isotônica, em condição basal (1,25 mM de cálcio), após elevação da concentração extracelular de cálcio para 5,2 mM e estimulação beta-adrenérgica com isoproterenol 1,0 µM. Fragmentos do VE foram usados para estudo de estresse oxidativo e microscopias óptica e eletrônica. RESULTADOS: As dietas suplementadas com AGS e AGI não alteraram a função mecânica do músculo cardíaco. Entretanto, ambas provocaram estresse oxidativo, com aumento do hidroperóxido de lipídio e redução da concentração de superóxido dismutase. A dieta AGI diminuiu a expressão da catalase e a AGS reduziu a quantidade de glutationa peroxidase miocárdica. Ambas as dietas promoveram discretas alterações morfológicas visualizadas ultra-estruturalmente, como depósitos lipídicos e lesões das membranas celulares. CONCLUSÃO: Os resultados sugerem que dietas enriquecidas com AGS e AGI não acarretam alteração da função mecânica do músculo cardíaco isolado, mas causam discretas lesões estruturais e estresse oxidativo no miocárdio. OBJECTIVES: To study the influence of saturated (SFA) and unsaturated fatty acid (UFA) rich diets on mechanical function, morphology and oxidative stress in rat myocardium. METHODS: Male, 60-day-old Wistar rats were fed a control (n=8), a SFA (n=8), or a UFA-rich diet (n=8) for sixty days. Mechanical function was studied in isolated left ventricle papillary muscle under isometric and isotonic contractions, in basal conditions (1.25mM calcium chloride) and after 5.2mM calcium chloride and beta-adrenergic stimuli with 1.0µM isoproterenol. Left ventricle fragments were used to study oxidative stress and morphology under light and electron microscopy. RESULTS: SFA and UFA-rich diets did not change myocardium mechanical function. Both diets caused oxidative stress, with high lipid hydroperoxide and low superoxide-dismutase concentrations. UFA rich diet decreased catalase expression and SFA rich diet decreased the amount of myocardial glutathione-peroxidase. Both diets promoted light ultrastructural injuries such as lipid deposits and cell membrane injuries. CONCLUSION: Results suggest that SFA and UFA rich diets do not alter isolated muscle mechanical function, but promote light myocardial morphological injuries and oxidative stress. UNESP Faculdade de Medicina de Botucatu Faculdade Médica UNESP Faculdade de Medicina de Botucatu Faculdade Médica

Made available in DSpace on 2015-12-07T15:31:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2015. Added 1 bitstream(s) on 2015-12-07T15:54:08Z : No. of bitstreams: 1 PMC4504040.pdf: 941585 bytes, checksum: 46278ddf901c5d0c061d5ba9e825ffa9 (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Pró-Reitoria de Pesquisa da UNESP (PROPe) Oxidative stress plays a major role in diabetic cardiomyopathy pathogenesis. Anti-oxidant therapy has been investigated in preventing or treating several diabetic complications. However, anti-oxidant action on diabetic-induced cardiac remodeling is not completely clear. This study evaluated the effects of rutin, a flavonoid, on cardiac and myocardial function in diabetic rats. Wistar rats were assigned into control (C, n = 14); control-rutin (C-R, n = 14); diabetes mellitus (DM, n = 16); and DM-rutin (DM-R, n = 16) groups. Seven days after inducing diabetes (streptozotocin, 60 mg/kg, i.p.), rutin was injected intraperitoneally once a week (50 mg/kg) for 7 weeks. Echocardiogram was performed and myocardial function assessed in left ventricular (LV) papillary muscles. Serum insulin concentration was measured by ELISA. One-way ANOVA and Tukey's post hoc test. Glycemia was higher in DM than DM-R and C and in DM-R than C-R. Insulin concentration was lower in diabetic groups than controls (C 2.45 ± 0.67; C-R 2.09 ± 0.52; DM 0.59 ± 0.18; DM-R 0.82 ± 0.21 ng/mL). Echocardiogram showed no differences between C-R and C. DM had increased LV systolic diameter compared to C, and increased left atrium diameter/body weight (BW) ratio and LV mass/BW ratio compared to C and DM-R. Septal wall thickness, LV diastolic diameter/BW ratio, and relative wall thickness were lower in DM-R than DM. Fractional shortening and posterior wall shortening velocity were lower in DM than C and DM-R. In papillary muscle preparation, DM and DM-R presented higher time to peak tension and time from peak tension to 50% relaxation than controls; time to peak tension was lower in DM-R than DM. Under 0.625 and 1.25 mM extracellular calcium concentrations, DM had higher developed tension than C. Rutin attenuates cardiac remodeling and left ventricular and myocardial dysfunction caused by streptozotocin-induced diabetes mellitus. Departamento de Medicina Interna, Faculdade de Medicina de Botucatu (FMB), Universidade Estadual Paulista (UNESP), Botucatu, SP, Brasil Departamento de Química e Bioquímica, Instituto de Biociências de Botucatu (IBB), Universidade Estadual Paulista (UNESP), Botucatu, SP, Brasil Departamento de Clínica Médica, Faculdade de Medicina de Botucatu (FMB), Universidade Estadual Paulista (UNESP), Botucatu, SP, Brasil Universidade Estadual Paulista, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu Universidade Estadual Paulista, Departamento de Química e Bioquímica, Instituto de Biociências de Botucatu CNPq: 306845/2012-1 CNPq: 306857/2012-0) FAPESP: 2009/54506-7

Piper amalago (Piperaceae) has been used in folk medicine as an analgesic. This study aimed to evaluate the pharmacological effects of extract and pure amides obtained from P. amalago on pain to provide a pharmacological basis for their use in traditional medicine.This study evaluated the anti-nociceptive, anti-hyperalgesic, anti-arthritic and anti-depressive activities of the ethanolic extract of P. amalago (EEPA) and the amides N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl] pyrrolidine (1) and N-[7-(3',4'-methylenedioxyphenyl)-2(E),4(E)-heptadienoyl] pyrrolidine (2) obtained from P. amalago in animal models.Mice treated daily with EEPA (100mg/kg, p.o.) were assayed for 20 days for knee edema (micrometer measurement), mechanical hyperalgesia (analgesiometer analysis), heat sensitivity and immobility (forced swim test) in the Complete Freund's Adjuvant (CFA) model. Cold (acetone test) and mechanical hyperalgesia (electronic von Frey analysis) responses were evaluated for 15 days in rats treated with oral EEPA (100mg/kg) in the spared nerve injury (SNI) model. Meanwhile, mice were evaluated for carrageenan-induced edema and mechanical hyperalgesia and for nociception using the formalin model after a single administration of EEPA (100mg/kg) or amides 1 and 2 (1mg/kg).Amides (1) and (2) were detected and isolated from the EEPA. The EEPA inhibited mechanical hyperalgesia, knee edema, and heat hyperalgesia, but not depressive-like behavior, induced by the intraplantar injection of CFA. When evaluated in the SNI model, the EEPA inhibited mechanical and cold hyperalgesia. The EEPA, 1 and 2 prevented the mechanical hyperalgesia induced by carrageenan and the anti-nociceptive effects in both phases of formalin nociception. The EEPA did not induce alterations in the open field test.The EEPA was effective for inhibition of pain and arthritic parameters but was not effective against depressive-like behavior; additionally, it did not alter locomotor activity. The amides obtained seemed to be the active component(s) present in the EEPA because they proved to be anti-nociceptive and anti-hyperalgesic in models of acute pain. Considering that few drugs are currently available for the treatment of chronic pain, especially neuropathic pain, the present results may have clinical relevance and open new possibilities for the development of new anti-hyperalgesic and anti-arthritic agents from P. amalago.

Univ Estadual Paulista Julio Mesquita Filho, Dept Morphol, BR-18618000 Botucatu, SP, Brazil

This study evaluated the effects of exercise training on myocardial function and ultrastructure of rats submitted to different levels of food restriction (FR). Male Wistar-Kyoto rats, 60 days old, were submitted to free access to food, light FR (20%), severe FR (50%) and/or to swimming training (one hour per day with 5% of load, five days per week for 90 days). Myocardial function was evaluated by left ventricular papillary muscle under basal condition (calcium 1.25 mM), and after extracellular calcium elevation to 5.2 mM and isoproterenol (1 microM) addition. The ultrastructure of the myocardium was examined in the papillary muscle. The training effectiveness was verified by improvement of myocardial metabolic enzyme activities. Both 20% and 50% food restriction protocols presented minor body and ventricular weights gain. The 20%-FR, in sedentary or trained rats, did not alter myocardial function or ultrastructure. The 50%-FR, in sedentary rats, caused myocardial dysfunction under basal condition, decreased response to inotropic stimulation, and promoted myocardial ultrastructural damage. The 50%-FR, in exercised rats, increased myocardial dysfunction under basal condition but increased response to inotropic stimulation although there was myocardial ultrastructural damage. In conclusion, the exercise training in severe restriction caused marked myocardial dysfunction at basal condition but increased myocardial response to inotropic stimulation.

Heart failure (HF) is characterized by a skeletal muscle myopathy with increased expression of fast myosin heavy chains (MHCs). The skeletal muscle-specific molecular regulatory mechanisms controlling MHC expression during HF have not been described. Myogenic regulatory factors (MRFs), a family of transcriptional factors that control the expression of several skeletal muscle-specific genes, may be related to these alterations. This investigation was undertaken in order to examine potential relationships between MRF mRNA expression and MHC protein isoforms in Wistar rat skeletal muscle with monocrotaline-induced HF. We studied soleus (Sol) and extensor digitorum longus (EDL) muscles from both HF and control Wistar rats. MyoD, myogenin and MRF4 contents were determined using reverse transcription-polymerase chain reaction while MHC isoforms were separated using polyacrylamide gel electrophoresis. Despite no change in MHC composition of Wistar rat skeletal muscles with HF, the mRNA relative expression of MyoD in Sol and EDL muscles and that of MRF4 in Sol muscle were significantly reduced, whereas myogenin was not changed in both muscles. This down-regulation in the mRNA relative expression of MRF4 in Sol was associated with atrophy in response to HF while these alterations were not present in EDL muscle. Taken together, our results show a potential role for MRFs in skeletal muscle myopathy during HF.

Univ Estadual Paulista Julio de Mesquita Filho, Fac Med Botucatu, Dept Clin Med, Botucatu, SP, Brazil

Previous works from our laboratory have revealed that food restriction (FR) promotes discrete myocardial dysfunction in young rats. We examined the effects of FR on cardiac function, in vivo and in vitro, and ultrastructural changes in the heart of middle-aged rats. Twelve-month-old Wistar-Kyoto rats were fed a control (C) or restricted diet (daily intake reduced to 50% of the control group) for 90 days. Cardiac performance was studied by echocardiogram and in isolated left ventricular (LV) papillary muscle by isometric contraction in basal condition, after calcium chloride (5.2 mM) and beta-adrenergic stimulation with isoproterenol (10(-6) M). FR did not change left ventricular function, but increased time to peak tension, and decreased maximum rate of papillary muscle tension development. Inotropic maneuvers promoted similar effects in both groups. Ultrastructural alterations were seen in most FR rat muscle fibers and included, absence and/or disorganization of myofilaments and Z line, hyper-contracted myofibrils, polymorphic and swollen mitochondria with disorganized cristae, and a great quantity of collagen fibrils. In conclusion, cardiac muscle sensitivity to isoproterenol and elevation of extracellular calcium concentration is preserved in middle-aged FR rats. The intrinsic muscle performance depression might be related to morphological damage.

OBJECTIVES:This study investigated the antidepressant and antinociceptive effects of ethanolic extract (SLEE) and pure fruticuline A obtained from Salvia lachnostachys leaves on rats and mice. METHODS:In this study, SLEE (100 mg/kg, p.o. route) was evaluated for its effects on spared nerve injury (SNI) in rats. The animals were submitted to mechanical sensitivity, forced swim (FST) and cold sensitivity tests 10 and 15 days after surgery. SLEE (100 mg/kg, p.o.) and fruticuline A (3 mg/kg, p.o.) were also evaluated with respect to nociceptive behavior induced by formalin. In addition, clonidine-induced depressive-like behavior was also analyzed. RESULTS:The oral administration of SLEE for up to 15 days and the subcutaneous injection of 10 mg/kg of ketamine (positive control) significantly inhibited SNI-induced mechanical hyperalgesia and decreased immobility in the FST. On the 15th day of oral treatment, SLEE prevented the SNI-induced increase in cold sensitivity. In the formalin test, SLEE and fruticuline A significantly reduced the frequency of paw licking during the first and second phases and decreased the formation of edema. In locomotor analysis (open field test without clonidine treatment), SLEE and fruticuline A did not alter the response. SLEE and fruticuline A significantly attenuated clonidine-induced suppression of spontaneous locomotor activity (squares invaded and licking) and emotionality (grooming and freezing) compared with controls, similar to the naive group. CONCLUSION:SLEE exhibits antihyperalgesic, antidepressant, and antinociceptive effects, and fruticuline A appears to be at least partly responsible for the effects of SLEE. Together, these results demonstrate the antidepressive effects of SLEE and fruticuline A and indicate that both derivatives obtained from S. lachnostachys act against spontaneous neuropathic pain.

Physical stress tolerance (ST) is a measurement of cardiorespiratory fitness. Aerobic capacity is reduced in heart failure (HF) although there is no data available on this parameter in animals with ventricular dysfunction and no signs of HF.Evaluate ST in rats with ventricular diastolic dysfunction isolated or associated with systolic dysfunction induced by ascending aortic stenosis (AoS).Young male Wistar rats (20-30 days old), divided in: control group (CG, n=11) and AoSG group, (n=12). Animals were assessed at 6 and 18 weeks after AoS surgery. Treadmill exercise test was until exhaustion and evaluated treadmill speed and lactate concentration [LAC] at lactate threshold, treadmill speed and [LAC] at exhaustion, and total testing time.Echocardiography data revealed remodeling of the left atrium and left ventricular concentric hypertrophy at 6 and 18 weeks. Endocardial fractional shortening was greater in AoSG than CG at 6 and 18 weeks. Midwall fractional shortening was greater in AoSG than in CG only 6 week. Cardiac index was similar in CG and AoSG at 6 and 18 weeks and decreased between from 6 to 18 weeks in both groups. The E wave to A wave ratio was greater in CG than in AoSG at both periods and did not change in both groups between week 6 and 18. Treadmill stress testing parameters were similar in both groups at 6 or 18 weeks.Although AoS promotes isolated diastolic dysfunction or associated with systolic dysfunction at 6 or 18 weeks, it is not sufficient to modify physical stress tolerance.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:41:21Z No. of bitstreams: 1 S0066-782X2011000900008.pdf: 317389 bytes, checksum: 050fa42a7102f7f1c3eac2678f8a8138 (MD5) Made available in DSpace on 2013-08-22T18:41:21Z (GMT). No. of bitstreams: 1 S0066-782X2011000900008.pdf: 317389 bytes, checksum: 050fa42a7102f7f1c3eac2678f8a8138 (MD5) Previous issue date: 2011-07-01 Made available in DSpace on 2013-09-30T19:27:50Z (GMT). No. of bitstreams: 2 S0066-782X2011000900008.pdf: 317389 bytes, checksum: 050fa42a7102f7f1c3eac2678f8a8138 (MD5) S0066-782X2011000900008.pdf.txt: 43869 bytes, checksum: 776bf0fb95907daa85e4d92e05ccaa4f (MD5) Previous issue date: 2011-07-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:07:41Z No. of bitstreams: 2 S0066-782X2011000900008.pdf: 317389 bytes, checksum: 050fa42a7102f7f1c3eac2678f8a8138 (MD5) S0066-782X2011000900008.pdf.txt: 43869 bytes, checksum: 776bf0fb95907daa85e4d92e05ccaa4f (MD5) Made available in DSpace on 2014-05-20T15:07:41Z (GMT). No. of bitstreams: 2 S0066-782X2011000900008.pdf: 317389 bytes, checksum: 050fa42a7102f7f1c3eac2678f8a8138 (MD5) S0066-782X2011000900008.pdf.txt: 43869 bytes, checksum: 776bf0fb95907daa85e4d92e05ccaa4f (MD5) Previous issue date: 2011-07-01 FUNDAMENTO: Treinamento físico (TF) aumenta a sensibilidade dos hormônios tireoidianos (HT) e a expressão gênica de estruturas moleculares envolvidas no movimento intracelular de cálcio do miocárdio, enquanto a restrição alimentar (RIA) promove efeitos contrários ao TF. OBJETIVO: Avaliar os efeitos da associação TF e RIA sobre os níveis plasmáticos dos HT e a produção de mRNA dos receptores HT e estruturas moleculares do movimento de cálcio do miocárdio de ratos. MÉTODOS: Utilizaram-se ratos Wistar Kyoto divididos em: controle (C, n = 7), RIA (R50, n = 7), exercício físico (EX, n = 7) e exercício físico + RIA (EX50, n = 7). A RIA foi de 50% e o TF foi natação (1 hora/dia, cinco sessões/semana, 12 semanas consecutivas). Avaliaram-se as concentrações séricas de triiodotironina (T3), tiroxina (T4) e hormônio tireotrófico (TSH). O mRNA da bomba de cálcio do retículo sarcoplasmático (SERCA2a), fosfolamban (PLB), trocador Na+/Ca+2 (NCX), canal lento de cálcio (canal-L), rianodina (RYR), calsequestrina (CQS) e receptor de HT (TRα1 e TRβ1) do miocárdio foram avaliados por reação em cadeia da polimerase (PCR) em tempo real. RESULTADOS: RIA reduziu o T4, TSH e mRNA do TRα1 e aumentou a expressão da PLB, NCX e canal-L. TF aumentou a expressão do TRβ1, canal-L e NCX. A associação TF e RIA reduziu T4 e TSH e aumentou o mRNA do TRβ1, SERCA2a, NCX, PLB e correlação do TRβ1 com a CQS e NCX. CONCLUSÃO: Associação TF e RIA aumentou o mRNA das estruturas moleculares cálcio transiente, porém o eixo HT-receptor não parece participar da transcrição gênica dessas estruturas. BACKGROUND: Chronic exercise and food restriction (FR) have directionally opposite changes in transcription of molecular structures of calcium handling and thyroid hormone (TH) status. OBJECTIVE: Evaluate the association of chronic exercise and FR on serum thyroid hormones and gene transcription of molecular structures of intracellular calcium transients and thyroid receptors in myocardium of rats. METHODS: Male Wistar Kyoto rats, divided into two groups: control (C, n = 7), FR (R50, n = 7), chronic exercise (EX, n = 7) and chronic exercise + FR (EX50, n = 7). FR was of 50% and exercise was swimming (1 hour/day, 5 days/week, during 12 weeks). Serum concentrations of T3, T4 and TSH were determined. The mRNA gene expression of the sarcoplasmatic reticulum calcium pump (SERCA2a), phospholamban (PLB), Na+/Ca+2 exchanger (NCX), calcium channel L-type (L-channel), ryanodine (RYR), calsequestrin (CQS) and HT receptor (TRα1 and TRβ1) of the myocardium was performed by PCR real-time. RESULTS: FR reduced serum levels of T4 and TSH and TRα1 mRNA and increased the expression of PLB, NCX and L-channel. Exercise increased the TRβ1 receptor, L-channel and NCX. The association of exercise and FR reduced plasma T4 and TSH, TRβ1 mRNA increase, SERCA2a, NCX and PLB, and there was a significant correlation of TRβ1 with CQS and NXC. CONCLUSION: Chronic exercise and food restriction increased the mRNA of transient Ca2+ proteins; however, TH-receptor axis cannot participate in the transcription of mRNA of myocardial calcium transient proteins. FUNDAMENTO: Entrenamiento físico (EF) aumenta la sensibilidad de las hormonas tiroideas (HT) y la expresión génica de estructuras moleculares envueltas en el movimiento intracelular de calcio del miocardio, mientras que la restricción alimenticia (RA) promueve efectos contrarios al EF. OBJETIVO: Evaluar los efectos de la asociación EF y RA sobre los niveles plasmáticos de los HT y la producción de ARNm de los receptores HT y estructuras moleculares del movimiento de calcio del miocardio de ratones. MÉTODOS: Se utilizaron ratones Wistar Kyoto divididos en: control (C, n = 7), RA (R50, n = 7), ejercicio físico (EX, n = 7) y ejercicio físico + RA (EX50, n = 7). La RA fue de 50% y el EF fue natación (1 hora/día, cinco sesiones/semana, 12 semanas consecutivas). Se evaluaron las concentraciones séricas de triyodotironina (T3), tiroxina (T4) y hormona tireotrófico (TSH). El ARNm de la bomba de calcio del retículo sarcoplasmático (SERCA2a), fosfolamban (PLB), intercambiador Na+/Ca+2 (NCX), canal lento de calcio (canal-L), rianodina (RYR), calsequestrina (CQS) y receptor de HT (TRα1 y TRβ1) del miocardio fueron evaluados por reacción en cadena de la polimerasa (PCR) en tiempo real. RESULTADOS: RA redujo el T4, TSH y ARNm del TRα1 y aumentó la expresión de la PLB, NCX y canal-L. EF aumentó la expresión del TRβ1, canal-L y NCX. La asociación EF y RA redujo T4 y TSH y aumentó el ARNm del TRβ1, SERCA2a, NCX, PLB y correlación del TRβ1 con la CQS y NCX. CONCLUSIÓN: Asociación EF y RA aumentó el ARNm de las estructuras moleculares calcio transiente, sin embargo el eje HT-receptor no parece participar de la transcripción génica de esas estructuras. Universidade Federal de Mato Grosso Instituto de Ciências da Saúde Universidade Estadual Paulista Faculdade de Medicina Universidade Estadual Paulista Faculdade de Medicina

Made available in DSpace on 2013-08-12T19:02:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-09-01 Made available in DSpace on 2013-09-30T18:16:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-09-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:33:20Z No. of bitstreams: 0 Made available in DSpace on 2014-05-20T13:33:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-09-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) FUNDAMENTO: Vários mecanismos têm sido propostos contribuir para a disfunção cardíaca em modelos de obesidade, tais como alterações nas proteínas do trânsito de cálcio (Ca+2) e nos receptores beta-adrenérgicos. Todavia, o papel desses fatores no desenvolvimento da disfunção miocárdica induzida pela obesidade ainda não está claro. OBJETIVO: Este estudo pretende investigar se a obesidade induzida por um ciclo de dieta hipercalóricas resulta em disfunção cardíaca. Além disso, foi avaliado se essa alteração funcional em ratos obesos está relacionada com o prejuízo do trânsito de Ca+2 e do sistema beta-adrenérgico. MÉTODOS: Ratos Wistar machos, 30 dias de idade, foram alimentados com ração padrão (C) e um ciclo de cinco dietas hipercalóricas (Ob) por 15 semanas. A obesidade foi definida pelo aumento da porcentagem de gordura corporal dos ratos. A função cardíaca foi avaliada mediante análise isolada do músculo papilar do ventrículo esquerdo em condições basais e após manobras inotrópicas e lusitrópicas. RESULTADOS: Em comparação com o grupo controle, os ratos obesos apresentaram aumento da gordura corporal e intolerância a glicose. Os músculos dos ratos obesos desenvolveram valores basais semelhantes; entretanto, as respostas miocárdicas ao potencial pós-pausa e aumento de Ca+2 extracelular foram comprometidas. Não houve alterações na função cardíaca entre os grupos após a estimulação beta-adrenérgica. CONCLUSÃO: A obesidade promove disfunção cardíaca relacionada com alterações no trânsito de Ca+2 intracelular. Esse prejuízo funcional é provavelmente ocasionado pela redução da atividade da bomba de Ca+2 do retículo sarcoplasmático (SERCA2a) via Ca+2 calmodulina-quinase. (Arq Bras Cardiol. 2011; [online].ahead print, PP.0-0) Background: Several mechanisms have been proposed to contribute to cardiac dysfunction in obesity models, such as alterations in calcium (Ca(2+)) handling proteins and beta-adrenergic receptors. Nevertheless, the role of these factors in the development of myocardial dysfunction induced by obesity is still not clear.Objective: The purpose of this study was to investigate whether obesity induced by hypercaloric diets results in cardiac dysfunction. Furthermore, it was evaluated whether this functional abnormality in obese rats is related to abnormal Ca(2+) handling and the beta-adrenoceptor system.Methods: Male 30-day-old Wistar rats were fed with standard food (C) and a cycle of five hypercaloric diets (Ob) for 15 weeks. Obesity was defined as increases in body fat percentage in rats. Cardiac function was evaluated by isolated analysis of the left ventricle papillary muscle under basal conditions and after inotropic and lusitropic maneuvers.Results: Compared with the control group, the obese rats had increased body fat and glucose intolerance. The muscles of obese rats developed similar baseline data, but the myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca(2+) were compromised. There were no changes in cardiac function between groups after beta-adrenergic stimulation.Conclusion: Obesity promotes cardiac dysfunction related to changes in intracellular Ca(2+) handling. This functional damage is probably caused by reduced cardiac sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) activation via Ca(2+) calmodulin kinase. (Arq Bras Cardiol 2011; 97(3) : 232-240) UFES Universidade Federal do Espírito Santo (UFES), Ctr Educ Fis & Desportos, Dept Desportos, Vitoria, ES, Brazil UNESP Univ Estadual Paulista Julio Mesquita Filho, Fac Med, Dept Clin Med, Botucatu, SP, Brazil UFMT Univ Fed Mato Grosso, Inst Ciencias Saude, Sinop, MT, Brazil UFMS Univ Fed Mato Grosso Sul, Dept Fisioterapia, Campo Grande, MS, Brazil UNESP Univ Estadual Paulista Julio Mesquita Filho, Inst Biociencias, Dept Bioestat, Botucatu, SP, Brazil UNESP Univ Estadual Paulista Julio Mesquita Filho, Fac Med, Dept Clin Med, Botucatu, SP, Brazil UNESP Univ Estadual Paulista Julio Mesquita Filho, Inst Biociencias, Dept Bioestat, Botucatu, SP, Brazil

Previous studies have shown that food restriction promotes myocardial dysfunction in rats. However, the molecular mechanisms that are responsible are unclear. We investigated the role of sarcoplasmic reticulum Ca2+-ATPase (SERCA2) on myocardial performance in food-restricted rats. Male Wistar–Kyoto rats, 60 days old, were fed a control or restricted diet (daily energy intake reduced to 50% of the control) for 90 days. Expression of Serca2a, phospholamban (PLB), Na+/Ca2+ exchanger (NCX), and thyroid hormone receptor (TRα1, TRβ1) mRNA was determined by quantitative PCR. SERCA2 activity was measured by using 20 µmol/L cyclopiazonic acid (CPA) in a left ventricular papillary muscle preparation during isometric contraction in basal conditions and during post-rest contraction. Serum concentrations of thyroxine (T4) and thyrotropin (TSH) were also determined. The 50%-restricted diet reduced body and ventricular weight and serum T4 and TSH levels. The interaction of CPA and food restriction reduced peak developed tension and maximum rate of tension decline (–dT/dt), but increased the resting tension intensity response during post-rest contraction. PLB and NCX mRNA were upregulated and TRα1 mRNA was downregulated by food restriction. These results suggest that food restriction promotes myocardial dysfunction related to impairment of sarcoplasmic reticulum Ca2+ uptake as a result of a hypothyroid state.

Food restriction (FR) has been shown to impair myocardial performance. However, the mechanisms behind these changes in myocardial function due to FR remain unknown. Since myocardial L-type Ca2+ channels may contribute to the cardiac dysfunction, we examined the influence of FR on L-type Ca2+ channels. Male 60-day-old Wistar rats were fed a control or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was evaluated in isolated left ventricular papillary muscles. The function of myocardial L-type Ca2+ channels was determined by using a pharmacological Ca2+ channel blocker, and changes in the number of channels were evaluated by mRNA and protein expression. FR decreased final body weights, as well as weights of the left and right ventricles. The Ca2+ channel blocker diltiazem promoted a higher blockade on developed tension in FR groups than in controls. The protein content of L-type Ca2+ channels was significantly diminished in FR rats, whereas the mRNA expression was similar between groups. These results suggest that the myocardial dysfunction observed in previous studies with FR animals could be caused by downregulation of L-type Ca2+ channels.

Background This study compared the influence of fasting/refeeding cycles and food restriction on rat myocardial performance and morphology. Methods Sixty-day-old male Wistar rats were submitted to food ad libitum (C), 50% food restriction (R50), and fasting/refeeding cycles (RF) for 12 weeks. Myocardial function was evaluated under baseline conditions and after progressive increase in calcium and isoproterenol. Myocardium ultrastructure was examined in the papillary muscle. Results Fasting/refeeding cycles maintained rat body weight and left ventricle weight between control and food-restricted rats. Under baseline conditions, the time to peak tension (TPT) was more prolonged in R50 than in RF and C rats. Furthermore, the maximum tension decline rate (−d T /d t ) increased less in R50 than in RF with calcium elevation. While the R50 group showed focal changes in many muscle fibers, such as the disorganization or loss of myofilaments, polymorphic mitochondria with disrupted cristae, and irregular appearance or infolding of the plasma membrane, the RF rats displayed few alterations such as loss or disorganization of myofibrils. Conclusion Food restriction promotes myocardial dysfunction, not observed in RF rats, and higher morphological damage than with fasting/refeeding. The increase in TPT may be attributed possibly to the disorganization and loss of myofibrils; however, the mechanisms responsible for the alteration in −d T /d t in R50 needs to be further clarified.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T19:00:14Z No. of bitstreams: 1 S0004-27302008000600007.pdf: 206637 bytes, checksum: bca1729a9c0823ed9cc22710f7d22be5 (MD5) Made available in DSpace on 2013-08-22T19:00:14Z (GMT). No. of bitstreams: 1 S0004-27302008000600007.pdf: 206637 bytes, checksum: bca1729a9c0823ed9cc22710f7d22be5 (MD5) Previous issue date: 2008-08-01 Made available in DSpace on 2013-09-30T19:58:27Z (GMT). No. of bitstreams: 2 S0004-27302008000600007.pdf: 206637 bytes, checksum: bca1729a9c0823ed9cc22710f7d22be5 (MD5) S0004-27302008000600007.pdf.txt: 29478 bytes, checksum: cfbb542e123d9cdadc55ffd1d04f279e (MD5) Previous issue date: 2008-08-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:15:04Z No. of bitstreams: 2 S0004-27302008000600007.pdf: 206637 bytes, checksum: bca1729a9c0823ed9cc22710f7d22be5 (MD5) S0004-27302008000600007.pdf.txt: 29478 bytes, checksum: cfbb542e123d9cdadc55ffd1d04f279e (MD5) Made available in DSpace on 2014-05-20T15:15:04Z (GMT). No. of bitstreams: 2 S0004-27302008000600007.pdf: 206637 bytes, checksum: bca1729a9c0823ed9cc22710f7d22be5 (MD5) S0004-27302008000600007.pdf.txt: 29478 bytes, checksum: cfbb542e123d9cdadc55ffd1d04f279e (MD5) Previous issue date: 2008-08-01 O objetivo do estudo foi desenvolver um ciclo de dietas hipercalóricas para promover obesidade em ratos. Ratos Wistar foram distribuídos em dois grupos: dieta normal (ND = 32; 3,5 kcal/g) e dietas hipercalóricas (HD; n = 32; 4,6 kcal/g). O grupo ND recebeu ração comercial e os animais HD um ciclo de diferentes dietas hipercalóricas, por 14 semanas. As variáveis analisadas foram peso corporal, parâmetros metabólicos e hormonais, pressão arterial sistólica e teste oral de tolerância à glicose. O nível de significância foi de 5%. O ciclo de dietas hipercalóricas promoveu aumento de peso e gordura corporal, pressão arterial sistólica e níveis séricos de glicose, triacilglicerol, insulina e leptina no grupo HD. Além disso, o grupo HD apresentou tolerância à glicose diminuída. em conclusão, os resultados deste estudo mostram que o ciclo de dietas hipercalóricas promove obesidade e exibe várias características comumente associadas com a obesidade humana, como aumento da pressão arterial, resistência à insulina, hiperglicemia, hiperinsulinemia, hiperleptinemia e dislipidemia. The present study was carried to develop and analyze the consequences of hypercaloric pellet-diet cycle that promotes obesity in rats. Male Wistar rats were randomly distributed into two groups that received either normal diet (ND; n =32; 3,5 Kcal/g) or a hypercaloric diet (HD; n =32; 4,6 Kcal/g). The ND group received commercial Labina rat feeding while the HD animals received a cycle of five hypercaloric diets over a 14-week period. The effects of the diets were analyzed in terms of body weight, body composition, hormone-metabolite levels, systolic arterial pressure and glucose tolerance at the 5% significance level. The hypercaloric pellet diet cycle promoted an increase in body weight and fat, systolic arterial pressure and a high serum level of glucose, triacylglycerol, insulin and leptin. The HD group also presented an impaired glucose tolerance. In conclusion, the results of this study show that the hypercaloric pellet-diet cycle promoted obesity in Wistar rats and displayed several characteristics that are commonly associated with human obesity, such as high arterial pressure, insulin resistance, hyperglycaemia, hyperinsulinaemia, hyperleptinaemia and dyslipidaemia. Universidade Estadual Paulista Faculdade de Medicina de Botucatu Clínica Médica Universidade Estadual Paulista Faculdade de Medicina de Botucatu Clínica Médica

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:52:47Z No. of bitstreams: 1 S0100-879X2008000700011.pdf: 553070 bytes, checksum: e3473dfe5311bd844caaef02f63eda5e (MD5) Made available in DSpace on 2013-08-22T18:52:47Z (GMT). No. of bitstreams: 1 S0100-879X2008000700011.pdf: 553070 bytes, checksum: e3473dfe5311bd844caaef02f63eda5e (MD5) Previous issue date: 2008-07-01 Made available in DSpace on 2013-09-30T18:17:37Z (GMT). No. of bitstreams: 2 S0100-879X2008000700011.pdf: 553070 bytes, checksum: e3473dfe5311bd844caaef02f63eda5e (MD5) S0100-879X2008000700011.pdf.txt: 23606 bytes, checksum: 63386660c4fde189986b365c173c16f6 (MD5) Previous issue date: 2008-07-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:33:37Z No. of bitstreams: 2 S0100-879X2008000700011.pdf: 553070 bytes, checksum: e3473dfe5311bd844caaef02f63eda5e (MD5) S0100-879X2008000700011.pdf.txt: 23606 bytes, checksum: 63386660c4fde189986b365c173c16f6 (MD5) Made available in DSpace on 2014-05-20T13:33:37Z (GMT). No. of bitstreams: 2 S0100-879X2008000700011.pdf: 553070 bytes, checksum: e3473dfe5311bd844caaef02f63eda5e (MD5) S0100-879X2008000700011.pdf.txt: 23606 bytes, checksum: 63386660c4fde189986b365c173c16f6 (MD5) Previous issue date: 2008-07-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Obesity is a complex multifactorial disorder that is often associated with cardiovascular diseases. Research on experimental models has suggested that cardiac dysfunction in obesity might be related to alterations in myocardial intracellular calcium (Ca2+) handling. However, information about the expression of Ca2+-related genes that lead to this abnormality is scarce. We evaluated the effects of obesity induced by a high-fat diet in the expression of Ca2+-related genes, focusing the L-type Ca2+ channel (Cacna1c), sarcolemmal Na+/Ca2+ exchanger (NCX), sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ryanodine receptor (RyR2), and phospholamban (PLB) mRNA in rat myocardium. Male 30-day-old Wistar rats were fed a standard (control) or high-fat diet (obese) for 15 weeks. Obesity was defined as increased percent of body fat in carcass. The mRNA expression of Ca2+-related genes in the left ventricle was measured by RT-PCR. Compared with control rats, the obese rats had increased percent of body fat, area under the curve for glucose, and leptin and insulin plasma concentrations. Obesity also caused an increase in the levels of SERCA2a, RyR2 and PLB mRNA (P < 0.05) but did not modify the mRNA levels of Cacna1c and NCX. These findings show that obesity induced by high-fat diet causes cardiac upregulation of Ca2+ transport_related genes in the sarcoplasmic reticulum. Universidade Estadual Paulista Faculdade de Medicina de Botucatu Departamento de Clínica Médica Universidade Estadual Paulista Departamento de Morfologia Universidade Estadual Paulista Instituto de Biociências Departamento de Bioestatística Universidade Estadual Paulista Faculdade de Medicina de Botucatu Departamento de Clínica Médica Universidade Estadual Paulista Departamento de Morfologia Universidade Estadual Paulista Instituto de Biociências Departamento de Bioestatística FAPESP: 07/53267-3 CNPq: 130572/2005-5

Made available in DSpace on 2013-08-12T17:49:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-01-01 Made available in DSpace on 2013-09-30T18:40:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:33:16Z No. of bitstreams: 0 Made available in DSpace on 2014-05-20T13:33:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-01-01 Fundação para o Desenvolvimento da UNESP (FUNDUNESP) The aim of the present study was to determine the classification error probabilities, as lean or obese, in hypercaloric diet-induced obesity, which depends on the variable used to characterize animal obesity. In addition, the misclassification probabilities in animals submitted to normocaloric diet were also evaluated. Male Wistar rats were randomly distributed into two groups: normal diet (ND; n=3 1; 3,5 Kcal/g) and hypercaloric diet (HD; n=31; 4,6 Kcal/g). The ND group received commercial Labina rat feed and HD animals a cycle of five hypercaloric diets for a 14-week period. The variables analysed were body weight, body composition, body weight to length ratio, Lee index, body mass index and misclassification probability A 5% significance level was used. The hypercaloric pellet-diet cycle promoted increase of body weight, carcass fat, body weight to length ratio and Lee index. The total misclassification probabilities ranged from 19.21 % to 40.91 %. In Conclusion, the results of this experiment show that rnisclassification probabilities Occur when dietary manipulation is used to promote obesity in animals. This misjudgement ranges from 19.49% to 40.52% in hypercaloric diet and 18.94% to 41.30% in normocaloric diet. São Paulo State Univ, UNESP, Botucatu Sch Med, Dept Clin Med, São Paulo, Brazil São Paulo State Univ, Inst Biol Sci, Dept Biostat, BR-18600000 Botucatu, SP, Brazil São Paulo State Univ, Inst Biol Sci, Dept Chem & Biochem, BR-18600000 Botucatu, SP, Brazil São Paulo State Univ, UNESP, Botucatu Sch Med, Dept Clin Med, São Paulo, Brazil São Paulo State Univ, Inst Biol Sci, Dept Biostat, BR-18600000 Botucatu, SP, Brazil São Paulo State Univ, Inst Biol Sci, Dept Chem & Biochem, BR-18600000 Botucatu, SP, Brazil

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2014-02-26T17:28:00Z No. of bitstreams: 1 WOS000243485600004.pdf: 482326 bytes, checksum: 41f05ba2581e13465d0b01594b2c15fc (MD5) Made available in DSpace on 2014-02-26T17:28:00Z (GMT). No. of bitstreams: 1 WOS000243485600004.pdf: 482326 bytes, checksum: 41f05ba2581e13465d0b01594b2c15fc (MD5) Previous issue date: 2007-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:32:52Z No. of bitstreams: 1 WOS000243485600004.pdf: 482326 bytes, checksum: 41f05ba2581e13465d0b01594b2c15fc (MD5) Made available in DSpace on 2014-05-20T13:32:52Z (GMT). No. of bitstreams: 1 WOS000243485600004.pdf: 482326 bytes, checksum: 41f05ba2581e13465d0b01594b2c15fc (MD5) Previous issue date: 2007-01-01 We have shown that myocardial dysfunction induced by food restriction is related to calcium handling. Although cardiac function is depressed in food-restricted animals, there is limited information about the molecular mechanisms that lead to this abnormality. The present study evaluated the effects of food restriction on calcium cycling, focusing on sarcoplasmic Ca2+-ATPase (SERCA2), phospholamban (PLB), and ryanodine channel (RYR2) mRNA expressions in rat myocardium. Male Wistar-Kyoto rats, 60 days old, were submitted to ad libitum feeding (control rats) or 50% diet restriction for 90 days. The levels of left ventricle SERCA2, PLB, and RYR2 were measured using semi-quantitative RT-PCR. Body and ventricular weights were reduced in 50% food-restricted animals. RYR2 mRNA was significantly decreased in the left ventricle of the food-restricted group (control = 5.92 +/- 0.48 vs food-restricted group = 4.84 +/- 0.33, P < 0.01). The levels of SERCA2 and PLB mRNA were similar between groups (control = 8.38 +/- 0.44 vs food-restricted group = 7.96 +/- 0.45, and control = 1.52 +/- 0.06 vs food-restricted group = 1.53 +/- 0.10, respectively). Down-regulation of RYR2 mRNA expressions suggests that chronic food restriction promotes abnormalities in sarcoplasmic reticulum Ca2+ release. Univ Estadual Paulista Julio Mesquita Filho, Fac Med Botucatu, Dept Clin Med, BR-18618000 Botucatu, SP, Brazil Univ Estadual Paulista, Dept Morfol, Botucatu, SP, Brazil Univ Estadual Paulista, Dept Bioestatist, Inst Biociencias Botucatu, Botucatu, SP, Brazil Univ Estadual Paulista Julio Mesquita Filho, Fac Med Botucatu, Dept Clin Med, BR-18618000 Botucatu, SP, Brazil Univ Estadual Paulista, Dept Morfol, Botucatu, SP, Brazil Univ Estadual Paulista, Dept Bioestatist, Inst Biociencias Botucatu, Botucatu, SP, Brazil

To analyze the potential contribution of contractility state and ventricular geometry to the development of heart failure in rats with aortic stenosis.Rats were divided into three groups: compensated aortic stenosis (AS, n=11), heart failure AS (n=12) and control rats (C, n=13).After 21 weeks, failing AS rats presented higher systolic (C=36.6+/-3.1, AS=78.6+/-4.8*, failing AS=104.6+/-7.8*(dagger)) and diastolic meridian stress (C=6.9+/-0.4, AS=20.1+/-1.1*, failing AS=43.2+/-3.2*(dagger)), hydroxyproline (C=3.6+/-0.7 mg/g, AS=6.6+/-0.6* mg/g, failing AS=9.2+/-1.4*(dagger) mg/g) and cross-sectional area (C=338+/-25 microm2, AS=451+/-32* microm2, failing AS=508+/-36*(dagger) microm2), in comparison with control and compensated AS animals (*p0.05 vs. control, (dagger)p0.05 vs. AS). In the isometric contraction study, considering the time from peak tension to 50% relaxation (RT50), the relative variation responses, following post-rest contraction and increase in Ca2+ concentration, were higher in failing AS than compensated AS animals. In contrast, following post-rest contraction, compensated AS group presented higher values of the peak developed tension (DT) than failing AS group. Following beta-adrenergic stimulation, control animals presented higher values of +dT/dt and -dT/dt than AS animals. In addition, failing AS animals presented higher TPT values than compensated AS animals.Myocardial contractile dysfunction contributes to the development of heart failure in rats with aortic stenosis.

Our last research showed that association of physical training (PT) and food restriction (FR) increases inotropic myocardial contractile response in rats.PURPOSE: To test the hypothesis that myocardial contractile response improvement in PT and FR rats is related to increase in the intracellular cal