Ursolic acid increases strength in mdx mice model and may decrease fibrosis deposition by tgf-ß downregulation / El ácido ursólico aumenta la resistencia en el modelo de ratones mdx y podría disminuir la deposición de fibrosis mediante la regulación decreciente de tgf-ß

SUMMARY: Dystrophin disfunction results in sarcolemma destabilization, leading muscle cell damage by continuous degeneration cycles and limited regeneration. In muscle dystrophy, caused by dystrophin dysfunction, inflammation, necrosis and fibrosis are pathophysiological muscle function loss characteristics. As a genetic disease, this muscle dystrophy has no cure, however, advances in drug therapy using glucocorticoids can decrease the disease progression. Subsequently, alternative therapies were studied, such as ursolic acid (UA), that inhibits muscle atrophy and increases muscle mass and strength. Herein, we used 10 mg/kg daily supplementation in mdx mice for 4 weeks to evaluate serum creatine phosphokinase (CPK), muscle strength (Kondziela test), muscular organization (histology) and expression of fibrosis related genes (TGF-ß, TNF-α, mstn and ostn). UA supplementation increased muscle morphological organization, motor strength and decreased muscular TGF-ß expression. Altogether, the gene expression profile, histological organization and strength could suggest that UA treatment did not stop the fibrogenesis but decreased its progress.

RESUMEN: La disfunción de la distrofina resulta en la desestabilización del sarcolema, llevando al daño de las células musculares por ciclos continuos de degeneración y regeneración limitada. En la distrofia muscular, debido a la disfunción de la distrofina, la inflamación, la necrosis y la fibrosis, son características fisiopatológicas de la pérdida de la función muscular. Como enfermedad genetica no es possible remediar esta distrofia muscular, sin embargo, los avances en la terapia de medicamentos con glucocorticoides pueden disminuir la progresión de la enfermedad. Se estudiaron terapias alternativas, como el ácido ursólico (UA), que inhibe la atrofia muscular y aumenta la masa y la fuerza muscular. En este estudio, utilizamos una suplementación diaria de 10 mg / kg en ratones mdx durante 4 semanas para evaluar la creatina fosfoquinasa (CPK) sérica, la fuerza muscular (prueba de Kondziela), la organización muscular (histología) y la expresión de genes relacionados con la fibrosis (TGF-ß, TNF- α, mstn y ostn). La suplementación con AU aumentó la organización morfológica muscular, la fuerza motora y la disminución de la expresión muscular de TGF-ß. El perfil de expresión génica, la organización histológica y la fuerza simultáneamente podrían sugerir que el tratamiento con AU no detuvo la fibrogénesis sino que disminuyó su progreso.

Síndrome de ALCAPA em uma Mulher Jovem / ALCAPA Syndrome in a Young Woman

Mulher de 18 anos com histórico de síncope, angina e palpitações há um ano. Uma indicação crucial era artéria coronária direita dilatada na ecocardiografia transtorácica. Os achados da tomografia computadorizada resultaram no diagnóstico da origem anômala da artéria coronariana esquerda proveniente da síndrome da artéria pulmonar.(AU)

Associação entre o índice de massa corporal e a gravidade e complexidade das lesões coronarianas em pacientes pós-infarto / Association of body mass index and coronary lesions severity and complexity in post-myocardial infarction patients

Objetivo: Avaliar a associação entre o índice de massa corporal e a gravidade das lesões coronarianas em pacientes com infarto agudo do miocárdio. Métodos: Coorte aninhada ao Catarina Heart Study que avaliou 350 indivíduos durante o primeiro evento de infarto agudo do miocárdio e o 30º dia pós-infarto. As variáveis qualitativas foram analisadas pelo teste do qui-quadrado. Após o resultado da distribuição, a avaliação de variáveis quantitativas foi feita pelo teste de t de Student, pela correlação de Pearson, pelo teste de Mann-Whitney e pela correlação de Spearman. Resultados: Indivíduos com obesidade G2 (15,4%) tiveram maior probabilidade de trombose em 30 dias em comparação a indivíduos com índice de massa corporal normal (1,1%), com p=0,005. Indivíduos com obesidade grau 1 (6,0%) e obesidade grau 2 (7,7%) tiveram mais eventos de infarto agudo do miocárdio em 30 dias em comparação a indivíduos com índice de massa corporal normal (0,0%), com p=0,019 e p=0,009, respectivamente. Nenhuma associação significativa foi encontrada em termos de fração de ejeção do ventrículo esquerdo, mortalidade e complexidade das lesões coronarianas (escore SYNTAX e TIMI frame count). Conclusão: A obesidade em diversos graus está diretamente associada a fatores de risco para doença cardiovascular, como hipertensão arterial sistêmica, dislipidemia e tabagismo. Não houve associação entre o índice de massa corporal com a gravidade das lesões coronarianas ou a fração de ejeção do ventrículo esquerdo. Não houve diferença na mortalidade comparando-se indivíduos com índice de massa corporal elevado a pacientes com índice de massa corporal normal. Pacientes com obesidade tiveram mais desfechos cardiovasculares, como trombose e novo evento de infarto agudo do miocárdio em 30 dias, ao serem comparados a pacientes com índice de massa corporal normal. Outros desfechos de seguimento em 30 dias não estiveram associados ao índice de massa corporal.

Objective: To evaluate the association between body mass index and severity of coronary lesions in patients with acute myocardial infarction. Methods: A cohort nested to Catarina Heart Study, which evaluated 350 individuals during the first event of myocardial infarction and the 30th day post-infarction. Qualitative variables were analyzed using the Chi-square test. After the distribution result, the evaluation of quantitative variables was done through Student's t-test, Pearson's correlation, Mann Whitney's test, and Spearman's correlation. Results: Individuals with G2 obesity (15.4%) had a greater probability of having thrombosis in 30 days compared to individuals with normal body mass index (1.1%), p=0.005. Individuals with G1 obesity (6.0%) and G2 obesity (7.7%) had more events of myocardial infarction in 30 days compared to individuals with normal body mass index (0.0%), with p=0.019 and p=0.009, respectively. No significant association was found in terms of left ventricle ejection fraction, mortality, and complexity of coronary lesions (SYNTAX score and TIMI frame count). Conclusion: Obesity in several degrees is directly associated with risk factors for cardiovascular disease, such as hypertension, dyslipidemia, and smoking. There was no association between the body mass index and the severity of coronary lesions or left ventricle ejection fraction. There was no difference in mortality comparing individuals with high body mass index to patients with normal body mass index. Patients with obesity had more cardiovascular outcomes, such as thrombosis and a new event of myocardial infarction in 30 days when compared to patients with normal body mass index. Other follow-up outcomes in 30 days were not associated with body mass index

Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-κB/NLRP3 signaling pathway

Abstract Purpose: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. Methods: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. Results: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1β, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. Conclusion: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.

Local and systemic effects caused by Crotalus durissus terrificus, Crotalus durissus collilineatus, and Crotalus durissus cascavella snake venoms in swiss mice

Abstract INTRODUCTION: Crotalus envenomations cause serious complications and can be fatal without appropriate treatment. Venom isoforms present and inter/intraspecific variations in the venom composition can result in different symptoms presented by bites by snakes from the same species but from different geographical regions. We comparatively evaluated the local and systemic effects caused by Crotalus durissus terrificus (Cdt), C.d. collilineatus (Cdcolli), and C.d. cascavella (Cdcasc) envenomation. METHODS: Venom chromatography was performed. Proteolytic, phospholipase, and LAAO activities were analyzed. Edema, myotoxicity, hepatotoxicity, nephrotoxicity, and coagulation alterations were evaluated. RESULTS: The venom SDS-PAGE analyses found the presence of convulxin, gyroxin, crotoxin, and crotamine in Cdt and Cdcolli venoms. Crotamine was not present in the Cdcasc venom. Cdt, Cdcollli, and Cdcasc venoms had no proteolytic activity. Only Cdcasc and Cdt venoms had phospholipase activity. LAAO activity was observed in Cdcolli and Cdcasc venoms. Cdcolli and Cdcasc venoms caused 36.7% and 13.3% edema increases, respectively. Cdt venom caused a 10% edema induction compared to those by other venoms. All venoms increased TOTAL-CK, MB-CK, and LDH levels (indicating muscle injury) and ALT, AST, GGT, and ALP levels (markers of liver damage) and were able to induce a neuromuscular blockade. Urea and creatinine levels were also altered in both plasma and urine, indicating kidney damage. Only Cdcolli and Cdcasc venoms increased TAPP and TAP. CONCLUSIONS: Together, these results allow us to draw a distinction between local and systemic effects caused by Crotalus subspecies, highlighting the clinical and biochemical effects produced by their respective venoms.

Hipercalcemia severa en el curso de rabdomiolisis: caso clínico / Rhabdomyolysis and severe hypercalcemia: report of one case

Rhabdomyolysis (RD) is the process that leads to cell destruction of striated muscle. Causes include inherited metabolic defects or acquired disorders. RD is frequently associated with acute kidney injury (AKI) and disorders of calcium metabolism. We report a 33 year old man that after amphetamine consumption and an uninterrupted 3,000 km driving presented vomiting, muscle pain and dark urine. He had elevated creatinkinase levels, severe hypocalcemia and an acute renal failure. He was treated with hemodialysis and calcitriol. He was transferred to our hospital and on admission a serum calcium of 18 mg/dl was detected. He continued on hemodialysis, recovering renal function and with normalization of creatinkinase levels and serum calcium level.

Acute responses of high-intensity circuit training in women: Low physical fitness levels show higher muscle damage / Respostas agudas de um circuito de treino de alta intensidade em mulheres: Níveis baixos de aptidão física apresentam maior dano muscular

High-intensity intermittent exercise (HIIE) elicits large improvements in health and cardiorespiratory fitness (CRF). HIIE can be applied with calisthenics exercises to improve strength and endurance. The acute effects of high-intensity circuit training (HICT) considering different CRF on myological variables are unknown. The aim was measure acute effects of HICT in young women considering different levels of CRF. Twelve women were allocated in two groups, who achieve 41mLO2•kg-1•min-1 or more= High Physical Fitness (HPF, n=5) and who achieve less than 41mLO2•kg-1•min-1= Low Physical Fitness (LPF,n=7). Protocol: 2x4 sets of 20 seconds at maximum intensity (all-out fashion) interspersed with 10 seconds of passive rest (jumping jacks, squat and thrust using 2kg dumbbells, mountain climber, and burpees). Blood samples were collected before, immediately after, 15minutes, 30minutes, one hour and 24 hours after. Heart rate, serum myoglobin, lactate, and creatine kinase (CK) concentration were analyzed. The HR achieved 94.1±3.7% of HRmax for LPF and 104.5±20.3% for HPF, p=0.03. The mean of delta lactate was similar between groups. The highest myoglobin has reached at 1h after the exercise protocol, with 50.0±30.2 ng/mL for LPF and 36.9±9.25 ng/mL for HPF. The delta of total CK before and after the exercise protocol shows that the serum CK level in LPF was significantly higher than HPF group (p=0.042). HICT composed by calisthenic protocol produced elevated and similar effects on HRmax, serum lactate and myoglobin in the woman with HPF and LPF. However, LPF group presented higher muscle damage inferred by serum CK concentrations.

O exercício intermitente de alta intensidade(HIIE) melhora a saúde e a aptidão cardiorrespiratória(CRF). HIIE pode ser aplicado com exercícios calistênicos para melhorar a força e resistência. Os efeitos agudos do treinamento de alta intensidade(HICT) considerando diferentes CRF em variáveis miológicas são desconhecidos. O objetivo foi medir os efeitos agudos do HICT em mulheres jovens, considerando diferentes níveis de CRF. Elas foram alocadas pelo nível de VO2máx. em dois grupos, as que atingiram 41mLO2•kg-1•min-1 ou mais= alta aptidão física(HPF,n=5) e menos de 41mLO2•kg-1•min-1= baixo aptidão física(LPF,n=7). Protocolo: 2x4 séries de 20s com intensidade máxima (all-out) intercalados com 10s de repouso passivo (jumping jacks, squat and thrust usando halteres 2kg, mountain climber e burpees). Sangue foi coletado antes, zero, 15, 30min, 1h e 24hs depois. Foram analisadas, freqüência cardíaca, mioglobina sérica, lactato e creatina quinase (CK). A FC alcançou 94,1±3,7% da FCmax para LPF e 104,5±20,3% para HPF, p=0,03. A média do delta lactato foi semelhante entre os grupos. O pico de mioglobina foi 1h após o protocolo de exercício, com 50.0±30.2ng/mL para LPF e 36.9±9.25ng/mL para HPF. O delta de CK total antes e depois do protocolo de exercício mostra que o nível sérico de CK no LPF foi significativamente maior do que o grupo HPF(p=0,042). O HICT com exercícios calistênicos produziu efeitos elevados e semelhantes sobre FCmax, lactato sérico e mioglobina nas mulheres com alta e baixa aptidão física. No entanto, o grupo LPF apresentou maior dano muscular inferido pelas concentrações séricas de CK.

Cardioprotective effect of lipstatin derivative orlistat on normotensive rats submitted to cardiac ischemia and reperfusion

Abstract Purpose: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. Methods: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB). Results: Treatment with ORL has been able to decrease the incidence of VA, AVB and LET. Besides that, treatment with ORL reduced serum concentrations of CK and LDL, but did not alter the levels of serum concentration of TG, VLDL and HDL. Conclusion: The reduction of ventricular arrhythmias, atrioventricular block, and lethality and serum levels of creatine kinase produced by treatment with orlistat in animal model of cardiac isquemia/reperfusion injury suggest that ORL could be used as an efficient cardioprotective therapeutic strategy to attenuate myocardial damage related to acute myocardial infarction.

Hyaluronic acid in dermatomyositis and polymyositis: relationship with disease and cutaneous lesions

Abstract: Background: There are scarce studies in the literature about hyaluronic acid in systemic autoimmune myopathies. Objectives: To analyze the serum level of hyaluronic acid in patients with dermatomyositis and polymyositis. Methods: Cross-sectional study, single-center, that evaluated hyaluronic acid in 18 dermatomyositis and 15 polymyositis (Bohan and Peter criteria), newly diagnosed, with clinical and laboratory activity, with no previous drug treatment. The patients were also age-, gender- and ethnicity-matched to 36 healthy individuals. The hyaluronic acid was analyzed by ELISA/EIA kit anti-hyaluronic acid. Results: There was a higher serum level of hyaluronic acid in patients with autoimmune myopathies, in relation to control group (P<0.05). Moreover, the serum level of this glycosaminoglycan was higher in dermatomyositis, when compared to polymyositis. Both groups were comparable with regard to demographic, clinical and laboratory data, except for the presence of skin lesions in the first group. Study limitations. The presence of hyaluronic acid in cutaneous lesions, particularly of patients with dermatomyositis, was not analyzed neither quantified. In addition, due to disease rarity and the establishment of strict inclusion and exclusion criteria, there was a small sample in the present study. Conclusions: As an example of others systemic autoimmune diseases, it is possible that the hyaluronic acid is involved in the pathogenesis of autoimmune myopathies, and particularly when associated with cutaneous lesions.

McArdle's disease: an underestimated or underdiagnosed myopathy in rheumatologic practice? Cases series and literature review / Doença de mcardle: uma miopatias subestimada e subdiagnosticada na pratica reumatológica? série clínica e revisão de literatura

OBJECTIVE: McArdle's disease is a metabolic myopathy that manifests with varied clinical conditions and is often confounded with other diagnoses. Herein, the authors report a case series and carry out a literature review. METHODS: A cross-sectional single-center study evaluating 12 patients with McArdle's disease was conducted. RESULTS: Mean age at onset of symptoms was 28.0±17.4 years, while age at disease diagnosis was 39.0±14.8 years. History of intolerance to physical exercises was observed in 10 cases; muscle weakness in 9, second wind phenomenon in only 1 case. The presence of cramps, fatigue and myalgia was observed in 12, 11 and 9 of the cases respectively. Median creatine phosphokinase level was 5951U/L. Most of the patients (83.3%) were initially diagnosed with another condition (polymyositis, inclusion body myositis, fibromyalgia and/or muscular dystrophy), and approximately half had received glucocorticoids and/or immunosuppressants prior to definitive diagnosis. All patients underwent muscular biopsy, which revealed the presence of subsarcolemmal vacuoles characterized by glycogen deposits, and negative histochemical reaction for the myophosphorylase enzyme. CONCLUSION: The present study reinforces the presence of clinical variability among patients and shows that McArdle's disease should be considered one of the differential diagnoses of inflammatory myopathies and other rheumatic diseases.

OBJETIVO: A doença de McArdle é uma miopatia metabólica que se manifesta com condições clínicas variadas e muitas vezes é confundida com outros diagnósticos. Os autores relatam uma série de casos e realizam uma revisão de literatura. MÉTODOS: Estudo transversal de um único centro em que foram avaliados 12 pacientes com doença de McArdle. RESULTADOS: A média de idade no início dos sintomas foi de 28,0±17,4 anos, enquanto a idade no diagnóstico da doença foi de 39,0±14,8 anos. História de intolerância ao exercício físico foi observada em 10 dos casos; fraqueza muscular em 9; fenômeno do "second wind" em apenas 1 caso. A presença de câimbras, fadiga e mialgia foi observada, respectivamente, em 12, 11 e 9 dos casos. O nível mediano de creatinafosfoquinase foi de 5951U/L. Oito pacientes foram inicialmente diagnosticados com outra condição (polimiosite, miosite de corpos de inclusão, fibromialgia e/ou distrofia muscular), e aproximadamente metade havia recebido glicocorticoides e/ou imunossupressores antes do diagnóstico definitivo. Todos os pacientes foram submetidos à biópsia muscular, que revelou a presença de vacúolos subsarcolêmicos caracterizados por depósitos de glicogênio e reação histoquímica negativa para a enzima miofosforilase. CONCLUSÕES: O presente estudo reforça a presença de variabilidade clínica entre pacientes e mostra que a doença de McArdle deve ser considerada um dos diagnósticos diferenciais de miopatias inflamatórias e outras doenças reumáticas.

Spontaneous pneumomediastinum in dermatomyositis: a case series and literature review / Pneumomediastino espontâneo na dermatomiosite: uma série de casos e revisão de literatura

OBJECTIVES: To describe a case series of spontaneous pneumomediastinum in dermatomyositis and to review the literature. METHODS: This was a retrospective single-center case series, reporting 9 patients with pneumomediastinum and defined dermatomyositis, followed from 2005 to 2017. RESULTS: Median age of patients: 33 years; cutaneous and pulmonary involvement in all cases; constitutional symptoms in 88.8% of patients; involvement of the joints in 11.1%, gastrointestinal tract in 44.4%, and muscles in 77.7%; subcutaneous emphysema was observed in 55.5% and pneumothorax in 11.1%, respectively. Muscle weakness was observed in 77.7% of cases and with a median level of serum creatine phosphokinase of 124U/L. Drawing on results for our literature review, the overall analysis showed that the risk factors associated with spontaneous pneumomediastinum were: (a) a history of interstitial pneumopathy; (b) normal or low levels of muscle enzymes; (c) previous use of systemic glucocorticoid; (d) over 50% of patients had subcutaneous emphysema; (e) high mortality as a consequence of severity of the interstitial lung disease. CONCLUSIONS: Our case series revealed that pneumomediastinum is a rare complication in dermatomyositis that occurs in patients with a history of interstitial pneumopathy and may be accompanied by subcutaneous emphysema and pneumothorax.

OBJETIVOS: Descrever série de casos de pneumomediastino espontâneo em portadores de dermatomiosite e revisar a literatura. MÉTODOS: Trata-se de série de casos, único centro, relatando 9 pacientes com pneumomediastino e dermatomiosite definida, acompanhados de 2005 a 2017. RESULTADOS: A mediana da idade dos pacientes foi de 33 anos. Sintomas constitucionais estavam presentes em 88,8% dos pacientes. Houve acometimento cutâneo e pulmonar em todos os casos, acometimento das articulações em 11,1%, trato gastrointestinal em 44,4% e musculatura em 77,7% dos pacientes. Enfisema subcutâneo foi observado em 55,5% e pneumotórax em 11,1%, respectivamente. A fraqueza muscular foi observada em 77,7% dos casos, com um nível médio de creatinofosfoquinase sérica de 124U/L. Com base nos resultados da revisão da literatura, a análise geral mostrou que: os fatores de risco associados ao pneumomediastino espontâneo foram: história de pneumopatia intersticial, níveis normais ou baixos de enzimas musculares, uso prévio de glicocorticoide sistêmico; >50% dos pacientes tiveram enfisema subcutâneo; houve alta mortalidade como consequência da gravidade da doença pulmonar intersticial. CONCLUSÕES: Nossa série de casos revelou que o pneumomediastino é uma complicação rara na dermatomiosite e que ocorre em pacientes com história de pneumopatia intersticial e pode ser acompanhada por enfisema subcutâneo e pneumotórax.

Insulin resistance is increased in adult patients with dermatomyositis / Resistência insulínica aumentada em pacientes com dermatomiosite

OBJECTIVE: To evaluate insulinemia in glucocorticoid naïve patients with dermatomyositis and to evaluate insulin resistance using the homeostatic model assessment of insulin resistance (HOMA2-IR). METHODS: This cross-sectional study included 25 dermatomyositis, non-diabetic glucocorticoid naïve patients. The control group consisted of 50 volunteers matched for age, gender, ethnicity, weight and height. The HOMA2-IR index was calculated from baseline insulin and glucose data. The International Myositis Assessment & Clinical Studies Group (IMACS) parameters were used to evaluate disease status. RESULTS: Mean age of the patients was 43.5 years and these were predominantly females. Patients had low disease activity according to IMACS parameters. Higher body mass index and waist circumference were observed in the dermatomyositis group compared to the control group. Insulin level and HOMA2-IR were also higher in patients with dermatomyositis. Moreover, analyzing dermatomyositis alone, the HOMA2-IR index correlated positively with weight, body mass index and waist circumference and was independent on disease status parameters. CONCLUSIONS: Patients with dermatomyositis had higher values for basal insulinemia, insulin resistance, body mass index and waist circumference. Moreover, HOMA2-IR moderately correlated with these anthropometric parameters. These metabolic abnormalities are related to the development of metabolic syndrome, one of the main comorbidities observed in dermatomyositis.

OBJETIVO: Avaliar a insulinemia em pacientes com dermatomiosite virgens de glicocorticoide e avaliar a resistência insulínica, utilizando o modelo de avaliação da homeostase de resistência insulínica (HOMA2-IR). MÉTODOS: Este estudo transversal incluiu 25 pacientes com dermatomiosites, não-diabéticos e sem uso prévio de glicocorticoides. Para o grupo de controle, 50 voluntários foram pareados por idade, gênero, etnia, peso e estatura. O índice HOMA2-IR foi calculado a partir de dados basais de insulina e glicose. Os parâmetros do International Myositis Assessment & Clinical Studies Group (IMACS) foram utilizados para avaliar o status da doença. RESULTADOS: A méda de idade dos pacientes foi de 43,5 anos, predominantemente do sexo feminino. Os pacientes apresentaram baixa atividade de doença de acordo com os parâmetros do IMACS. O índice de massa corporal e a circunferência da cintura foram maiores no grupo da dermatomiosite em comparação com o grupo controle. O nível de insulina e o HOMA2-IR também foram maiores em pacientes com dermatomiosite. Além disso, analisando a dermatomiosite isoladamente, o índice HOMA2-IR correlacionou-se positivamente com o peso, o índice de massa corporal e a circunferência da cintura e foi independente dos parâmetros de status da doença. CONCLUSÕES: Pacientes com dermatomiosite apresentam valores mais elevados de insulinemia basal, resistência à insulina, índice de massa corporal e circunferência da cintura. Além disso, o HOMA2-IR está moderadamente correlacionado com esses parâmetros antropométricos. Essas anormalidades metabólicas estão relacionadas ao desenvolvimento da síndrome metabólica, uma das principais comorbidades observadas na dermatomiosite.

Factors associated with changes in creatine phosphokinase (CPK) in trauma patients submitted to the "Red Wave", with evolution to rhabdomyolysis / Fatores associados à variação da creatina fosfoquinase (CPK) em pacientes vítimas de trauma, submetidos à "Onda Vermelha", com evolução à rabdomiólise

ABSTRACT Objective: to identify and analyze factors associated with plasma creatine phosphokinase (CPK) levels in trauma victims with progression to rhabdomyolysis. Methods: we conducted a prospective, longitudinal study, with 50 patients submitted to the "Red Wave" protocol, with evolution to rhabdomyolysis after hospital admission. We studied the variables age, gender, trauma scores, mechanism and outcome, CPK at admission and final, intervals of days between laboratory evaluations, surgery and complications. We stratified CPK values in <500U/L, ≥500 - <1000 U/L, and ≥1000U/L, with calculation of the difference between the initial and final values. Results: at admission, 83% of patients (n=39) had CPK≥1000U/L, with predominance of blunt trauma and thoracic injury (p<0.05), as well as orthopedic fracture, acute renal failure and gastrointestinal bleeding, CPK being lower in those without acute renal injury, with a trend towards statistical significance. There were no differences in final CPK stratification. Factors that were independently associated with the greater CPK variation were, positively, hospitalization time greater than one week and compartment syndrome, and negatively, acute renal injury. Conclusion: the CPK level of 1000U/L remains the lower limit, with importance for early intervention in worsening conditions such as digestive hemorrhage, acute renal injury and compartment syndrome, which implied greater absolute differences between initial and final CPK, in addition to blunt trauma, thoracic injury and orthopedic fracture.

RESUMO Objetivo: identificar e analisar fatores associados à variação dos níveis plasmáticos de creatina fosfoquinase (CPK) em vítimas de trauma com evolução à rabdomiólise. Métodos: estudo longitudinal prospectivo, com 50 pacientes que seguiram para o protocolo "Onda Vermelha", com evolução à rabdomiólise, após admissão hospitalar. Foram estudadas as variáveis: idade, sexo, escores, mecanismo e desfecho de trauma, CPK na admissão e final, intervalos de dias entre as avaliações laboratoriais, realização de cirurgia e complicações. Os valores da CPK foram estratificados em <500U/L; ≥500 - <1000 U/L; ≥1000U/L, com cálculo da diferença entre os valores inicial e final. Resultados: à admissão, 83% dos pacientes (n=39) apresentavam CPK≥1000U/L, com predomínio de trauma contuso e lesão torácica (p<0,05), além de fratura ortopédica, lesão renal aguda e hemorragia digestiva, sendo que a CPK era menor naqueles sem lesão renal aguda, com tendência à significância estatística. Não houve diferenças na estratificação por CPK final. Fatores que se revelaram independentemente associados à maior variação da CPK foram, positivamente, o tempo de internação superior a uma semana e síndrome compartimental, e negativamente, lesão renal aguda. Conclusão: como achado, nível de CPK de 1000U/L permanece como limite inferior, com importância à intervenção precoce em condições de agravamento do quadro, como hemorragia digestiva, lesão renal aguda e síndrome compartimental, que implicaram maiores diferenças absolutas entre CPK inicial e final, além do trauma contuso, lesão torácica e fratura ortopédica.

Efeitos de um salgante isento de sódio sobre marcadores sanguíneos bioquímicos hepáticos, renais e cardíacos de ratos normo e hipertensos / Effects of a sodium-free salting agent on blood hepatic, renal and cardiac biochemical markers of normal and hypertensive rats

Introdução: A hipertensão arterial é um dos fatores de risco para doenças cardiovasculares, estando diretamente associada ao elevado consumo de sódio. Objetivo: Avaliar os níveis de marcadores de lesão hepática, renal e cardíaca em ratos hipertensos comparados aos seus controles normotensos, tratados com um salgante isento de sódio, água ou NaCl. Métodos: Ratos hipertensos (SHR) e seus controles normotensos (NWR) foram divididos em 3 grupos (n=7): G1 (água); G2 (solução aquosa contendo NaCl 70 mg/kg/dia); G3 (solução aquosa contendo salgante sem sódio 70 mg/kg/dia). Após 30 dias, o sangue dos animais foi processado. Resultados: Não houve diferença entre os níveis séricos de creatina quinase total, creatina quinase-MB, lactato desidrogenase, ácido úrico, aspartato aminotransferase e fosfatase alcalina tanto nos NWR como nos SHR tratados com NaCl ou Salgante. Houve diminuição da creatinina nos NWR e SHR tratados com NaCl e Salgante em relação aos controles (p<0,005). Conclusões: A suplementação diária com o Salgante e NaCl diminuiu os níveis séricos de creatinina nos grupos NWR e SHR. Contudo, não houve modificação nos níveis séricos de marcadores de lesão cardíaca e hepática. (AU)

Introduction: Hypertension is one of the risk factors for cardiovascular diseases, being directly associated with high consumption of sodium. Objective: To assess the levels of hepatic, renal and cardiac injury markers in hypertensive rats compared to their normotensive controls, treated with a salt free saline solution, water or NaCl. Methods: Hypertensive rats (SHR) and their normotensive controls (NWR) were divided into 3 groups (n = 7): G1 (water); G2 (aqueous solution containing NaCl 70 mg / kg / day); G3 (sodium salt-free aqueous solution 70 mg / kg / day). After 30 days, the animals' blood was processed. Results: There was no difference between serum levels of total creatine kinase, creatine kinase-MB, lactate dehydrogenase, uric acid, aspartate aminotransferase and alkaline phosphatase in both NWR and SHR1 treated NaCl or Salgante. There was a decrease in creatinine in NWR and SHR treated with NaCl and Salgante comparing to controls (p <0.005). Conclusions: Daily supplementation with sodium salt-free aqueous solution and NaCl decreases serum creatinine levels in NWR and SHR groups. However, there was no change in serum levels of cardiac and hepatic injury markers. (AU)

Single-dose lignocaine-based blood cardioplegia in single valve replacement patients

Abstract OBJECTIVE: Myocardial protection is the most important in cardiac surgery. We compared our modified single-dose long-acting lignocaine-based blood cardioplegia with short-acting St Thomas 1 blood cardioplegia in patients undergoing single valve replacement. METHODS: A total of 110 patients who underwent single (aortic or mitral) valve replacement surgery were enrolled. Patients were divided in two groups based on the cardioplegia solution used. In group 1 (56 patients), long-acting lignocaine based-blood cardioplegia solution was administered as a single dose while in group 2 (54 patients), standard St Thomas IB (short-acting blood-based cardioplegia solution) was administered and repeated every 20 minutes. All the patients were compared for preoperative baseline parameters, intraoperative and all the postoperative parameters. RESULTS: We did not find any statistically significant difference in preoperative baseline parameters. Cardiopulmonary bypass time were 73.8±16.5 and 76.4±16.9 minutes (P=0.43) and cross clamp time were 58.9±10.3 and 66.3±11.2 minutes (P=0.23) in group 1 and group 2, respectively. Mean of maximum inotrope score was 6.3±2.52 and 6.1±2.13 (P=0.65) in group 1 and group 2, respectively. We also did not find any statistically significant difference in creatine-phosphokinase-MB (CPK-MB), Troponin-I levels, lactate level and cardiac functions postoperatively. CONCLUSION: This study proves the safety and efficacy of long-acting lignocaine-based single-dose blood cardioplegia compared to the standard short-acting multi-dose blood cardioplegia in patients requiring the single valve replacement. Further studies need to be undertaken to establish this non-inferiority in situations of complex cardiac procedures especially in compromised patients.

Obesity, Serum Resistin and Leptin Levels Linked to Coronary Artery Disease / Obesidade, Soro Resistina e Níveis de Leptina Ligados à Doença Arterial Coronariana

Abstract Background: Clinical studies have demonstrated that adipocytokines play an important role in developing atherosclerotic cardiovascular diseases. Objective: The aim of study was to evaluate the relationship between serum resistin and leptin levels with obesity and coronary artery disease (CAD). Methods: In a cross-sectional study, we assessed the levels of serum resistin and leptin, C-reactive protein (CRP), lipid profile and cardiac enzyme tests (AST, CPK, LDH, CK-MB) in 40 CAD patients compared to 40 healthy controls. Anthropometric measurements including weight and height for calculating of body mass index (BMI), and waist circumference (WC) were performed for evaluation of obesity. Results: CAD patients had increased levels of leptin and CRP, (p < 0.001), cholesterol (p < 0.05), triglyceride (p < 0.01), and WC (p < 0.05) compared to healthy controls. There was no statistical difference between CAD and control subjects for resistin (p = 0.058). In a multiple regression analysis, only an association between serum leptin with BMI (β = 0.480, p < 0.05) and WC (β = 1.386, p < 0.05) was found. Conclusions: The findings suggest that leptin is a better marker of fat mass value than resistin and may be considered an independent risk factor for cardiac disorders that is largely dependent on obesity. However, further prospective studies are needed to confirm these results.

Resumo Fundamento: Estudos clínicos demonstraram que adipocitocinas têm papel importante no desenvolvimento de doenças cardiovasculares ateroscleróticas. Objetivo: Avaliar a relação entre níveis de leptina e resistina em soro com obesidade e doença arterial coronariana (DAC). Métodos: Em estudo transversal, avaliamos os níveis de resistina e leptina em soro, proteína C-reativa (CPR), perfil lipídico e testes de enzimas cardíacas (AST, CPK, LDH, CK-MB) em quarenta pacientes com DAC comparados a 40 controles saudáveis. Para avaliação de obesidade, foram feitas as medições antropométricas, incluindo peso e altura para o cálculo do índice de massa corporal (IMC) e circunferência da cintura (CC). Resultados: Pacientes com DAC apresentaram aumento nos níveis de leptina e CPR, (p < 0,001), colesterol (p < 0,05), triglicérides (p < 0,01) e CC (p < 0,05) em comparação aos controles. Não houve diferença significativa entre DAC e controles com relação à resistina (p = 0,058). Na análise de regressão múltipla, foi encontrada apenas uma associação entre leptina em soro ao IMC (β = 0,480, p < 0,05) e CC (β = 1,386, p < 0,05). Conclusões: Os achados sugerem que a leptina é melhor marcadora de valor de massa gorda do que a resistina, e pode ser considerada um fator de risco, dependente da obesidade, independente para distúrbios cardíacos. Contudo, outros estudos prospectivos serão necessários para a confirmação desses resultados.

Syndrome in question

Abstract: Dermatomyositis is a rare inflammatory disease, autoimmune, with proximal myopathy associated with characteristic dermatological manifestations. In adults, 20-50% of the cases are paraneoplastic manifestation, being mandatory the workup for malignancy Herein we report a case of a woman with classic dermatological presentation of dermatomyositis and newly diagnosed breast cancer. In general, the clinical presentation of paraneoplastic dermatomyositis is more exuberant and manifestations may precede, concur or succeed the diagnosis of neoplasia. The prognosis of cases associated with breast cancer is worse than the idiopathic form. Treatment is based mainly on the resolution of the underlying disease, beyond immunosuppressants.

Análise de biomarcadores séricos de lesão muscular durante competição de mountain bike / Analysis of muscle injury serum biomarkers during a mountain bike competition

Introdução: O estudo de biomarcadores musculares permite diagnóstico de futuras lesões no esporte de alto nível. Objetivo: Avaliar a creatinoquinase (CK) e lactato desidrogenase (LDH) em atletas Mountain Bike. Métodos: Foram coletadas amostras sanguíneas de dez atletas de Elite de Mountain Bike. As coletas de sangue foram realizadas 24 horas antes da prova (T1), imediatamente ao final da corrida (T2), uma hora após a corrida (T3) e 24 horas depois da competição (T4). Resultados: A CK se elevou da ordem de 100% em 24 horas após a competição. Já LDH aumentou 43% em T2, permanecendo elevado até 1h após competição. A correlação entre os dois marcadores apresentou o coeficiente r = 0,80. Conclusão: O acompanhamento das concentrações de CK e LDH neste experimento foi possível estimar a recuperação pós-competição dos atletas em níveis de lesão muscular, o que se converte em valiosa ferramenta para a planificação e periodização do treinamento.

Introduction: Biomarkers muscles allows diagnosis of future injuries in overall sport. Objective: Evaluate the creatine kinase (CK) and lactate dehydrogenase (LDH) in Mountain Bike athletes. Methods: Blood samples of ten athletes Elite Mountain Bike was collected. The samples of blood were taken 24 hours before (T1) immediately at the end (T2), one hour after the race (T3) and 24 hour after competition (T4). Results: The CK amounted to around 100 % in 24 hours after the competition. LDH already increased by 43 % and remaining high until 1 hour after competition. The correlation between the two biomarkers showed coefficient r = 0.80. Conclusion: The monitoring of concentrations of CK and LDH in this experiment it was possible to estimate muscle injury post-competition, which becomes a valuable tool for planning and periodization of training.

Dexmedetomidine decreases the inflammatory response to myocardial surgery under mini-cardiopulmonary bypass

Cardiopulmonary bypass (CPB) with extracorporeal circulation produces changes in the immune system accompanied by an increase in proinflammatory cytokines and a decrease in anti-inflammatory cytokines. We hypothesize that dexmedetomidine (DEX) as an anesthetic adjuvant modulates the inflammatory response after coronary artery bypass graft surgery with mini-CPB. In a prospective, randomized, blind study, 12 patients (4 females and 8 males, age range 42-72) were assigned to DEX group and compared with a conventional total intravenous anesthesia (TIVA) group of 11 patients (4 females and 7 males). The endpoints used to assess inflammatory and biochemical responses to mini-CPB were plasma interleukin (IL)-1, IL-6, IL-10, interferon (INF)-γ, tumor necrosis factor (TNF)-α, C-reactive protein, creatine phosphokinase, creatine phosphokinase-MB, cardiac troponin I, cortisol, and glucose levels. These variables were determined before anesthesia, 90 min after beginning CPB, 5 h after beginning CPB, and 24 h after the end of surgery. Endpoints of oxidative stress, including thiobarbituric acid reactive species and delta-aminolevulinate dehydratase activity in erythrocytes were also determined. DEX+TIVA use was associated with a significant reduction in IL-1, IL-6, TNF-α, and INF-γ (P<0.0001) levels compared with TIVA (two-way ANOVA). In contrast, the surgery-induced increase in thiobarbituric acid reactive species was higher in the DEX+TIVA group than in the TIVA group (P<0.01; two-way ANOVA). Delta-aminolevulinate dehydratase activity was decreased after CPB (P<0.001), but there was no difference between the two groups. DEX as an adjuvant in anesthesia reduced circulating IL-1, IL-6, TNF-α, and INF-γ levels after mini-CPB. These findings indicate an interesting anti-inflammatory effect of DEX, which should be studied in different types of surgical interventions.

Cardioprotection against experimental myocardial ischemic injury using cornin

Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.