Efficacy and mechanism of traditional chinese medicine gel in sports-related soft tissue injury / Eficácia e mecanismo do tradicional gel da medicina chinesa em lesões desportivas de tecidos moles / Eficacia y mecanismo del gel de medicina tradicional china en lesiones deportivas de tejidos blandos

ABSTRACT Soft tissue injury is the most common disease in orthopedics, and it is also the most easily neglected disease in sports. Without timely and effective treatment, it is easy to develop into malignant strain and seriously affect life and sports. In view of this, the aim of this study is to analyze the effect and mechanism of traditional Chinese medicine gel in treating such injuries in the light of the characteristics of sports-related soft tissue injury. The right gastrocnemius muscle injury was simulated in 36 adult male rats. Chinese medicine gel and tincture were used to treat it. The contents of interleukin, alanine aminotransferase, blood urea nitrogen and prostaglandin E2 in the blood of rats under different courses of treatment were analyzed to explore recovery in four rats. The results showed that the levels of interleukin and prostaglandin E2 in the blood of rats treated with drugs were significantly lower than those in the control group (p<0.05), indicating that both drugs have obvious therapeutic effects on soft tissue injury. The content of interleukin in the blood of the Chinese medicine gel group was slightly lower than that of the tincture group, indicating that the Chinese medicine gel could affect the recovery of soft tissue injury by affecting leukocyte interleukin. This result is helpful in the treatment of soft tissue injury in sports and to further improve the therapeutic effect of traditional Chinese medicine gel.

RESUMO A lesão dos tecidos moles é a doença mais comum na ortopedia, e é também a doença mais facilmente negligenciada nos esportes. Sem tratamento ágil e eficaz, facilmente evolui para luxações malignas, afetando seriamente a vida e a prática de esportes. Em vista disso, o objetivo deste estudo é analisar o efeito e o mecanismo do gel da medicina tradicional chinesa no tratamento de tais lesões, com base nas características da lesão dos tecidos moles relacionada à prática esportiva. Estimulou-se lesão do músculo gastrocnêmio direito em 36 ratos adultos. O gel e a tintura chinesa foram usados para o tratamento. Foram analisados os conteúdos de interleucina, alanina aminotransferase, ureia sanguínea azoto e prostaglandina E2 no sangue dos ratos sob diferentes tratamentos, de modo a explorar a recuperação de quatro ratos. Os resultados mostraram que os níveis de interleucina e prostaglandina E2 no sangue dos ratos tratados com medicamentos eram significativamente inferiores aos do grupo controle (p<0.05), indicando que ambos os fármacos têm efeitos terapêuticos óbvios sobre lesões dos tecidos moles. O teor de interleucina no sangue do grupo gel chinês medicinal mostrou-se ligeiramente inferior ao do grupo tintura, indicando que o gel medicinal chinês pode afetar a recuperação da lesão nos tecidos moles, afetando o leucócito interleucina. Este resultado é útil para o tratamento de lesões dos tecidos moles relacionadas à prática esportiva e para melhorar ainda mais o efeito terapêutico do gel da medicina chinesa tradicional.

RESUMEN La lesión de los tejidos blandos es la enfermedad más común en la ortopedia, y es también la enfermedad más fácilmente descuidada en los deportes. Sin tratamiento ágil y eficaz, fácilmente evolucionan a luxaciones malignas, afectando seriamente la vida y la práctica de deportes. En vista de eso, el objetivo de este estudio es analizar el efecto y el mecanismo del gel de la medicina tradicional china en el tratamiento de tales lesiones, con base en las características de la lesión de los tejidos blandos relacionada a la práctica deportiva. Se estimuló lesión del músculo gastrocnemio derecho en 36 ratones adultos. El gel y la tintura china fueron usados para el tratamiento. Fueron analizados los contenidos de interleucina, alanina aminotransferasa, urea sanguínea, nitrógeno y prostaglandina E2 en la sangre de los ratones bajo diferentes tratamientos, de modo de explorar la recuperación de cuatro ratones. Los resultados mostraron que los niveles de interleucina y prostaglandina E2 en la sangre de los ratones tratados con medicamentos eran significativamente inferiores a los del grupo control (p<0.05), indicando que ambos fármacos tienen efectos terapéuticos obvios sobre lesiones de los tejidos blandos. El tenor de interleucina en la sangre del grupo gel chino medicinal se mostró ligeramente inferior al del grupo tintura, indicando que el gel medicinal chino puede afectar la recuperación de la lesión en los tejidos blandos, afectando el leucocito interleucina. Este resultado es útil para el tratamiento de lesiones de los tejidos blandos relacionadas a la práctica deportiva y para mejorar aún más el efecto terapéutico del gel de la medicina china tradicional.

The therapeutic impact of probiotics on nonalcoholic fatty liver disease in pediatrics: a systematic review / Impacto terapêutico dos probióticos na doença hepática gordurosa não alcoólica em pediatria: uma revisão sistemática

ABSTRACT Objective: Evaluate the effects of probiotics use, compared with placebo, in pediatric patients with non-alcoholic fatty liver disease (NAFLD), using laboratorial and ultrasonographic parameters as outcomes. Methods: A systematic review of the literature was performed through MEDLINE and Lilacs databases. The articles selected were randomized controlled clinical trials published until November 2018, without any language restriction, dealing with pediatric patients with NAFLD. Patients were divided into 2 groups. One group received probiotic therapy and the other group, only received placebo. The primary outcome evaluated was the difference between the serum levels of alanine aminotransferase (ALT) before and after receiving probiotics or placebo. The secondary outcomes evaluated were the serum aspartate aminotransferase levels, body mass index, serum triglycerides, waist circumference and level of liver steatosis on the ultrasonography. Results: A total of 46 articles were recovered, and 3 articles were included in the qualitative analysis, totaling 128 patients. Two trials revealed a significant decrease of alanine aminotransferase levels after treatment with probiotics (Lactobacillus rhamnosus for 8 weeks; Bifidobacterium+Lactobacillus for 12 weeks), when compared to the placebo. The other variables did not show a statistically significant difference between both groups. Conclusions: Probiotic therapy has contributed to the reduction of ALT serum levels in pediatric patients with nonalcoholic fatty liver disease, which is in line with results found by other authors in scientific literature. Regarding the secondary outcomes, the use of probiotics did not show benefits or damages compared to placebo.

RESUMO Objetivo: Avaliar os efeitos do uso de probióticos em comparação com placebo, em pacientes pediátricos portadores de doença hepática gordurosa não alcoólica (DHGNA), utilizando parâmetros laboratoriais e ultrassonográficos como desfecho. Métodos: Revisão sistemática da literatura por meio das bases de dados Sistema Online de Busca e Análise de Literatura Médica (MEDLINE) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs). Foram selecionados ensaios clínicos controlados randomizados publicados até novembro de 2018, sem restrição de língua, com pacientes pediátricos portadores de DHGNA, divididos em dois grupos. Um grupo foi submetido à terapia probiótica e outro grupo recebeu somente placebo. O desfecho primário avaliado foi a comparação dos níveis de alanina aminotransferase (ALT) ao início e no fim do seguimento entre os grupos probiótico e placebo. Os desfechos secundários avaliados foram os níveis de aspartato aminotransferase sérico, índice de massa corpórea, triglicerídeos totais séricos, circunferência abdominal e grau de esteatose hepática à ultrassonografia abdominal. Resultados: Foram recuperados 46 artigos, sendo três incluídos na análise qualitativa, totalizando 128 pacientes. Dois estudos demonstraram redução significativa dos níveis de ALT com o uso de probiótico (Lactobacillus rhamnosus, por oito semanas; Bifidobacterium+Lactobacillus, por 12 semanas), em comparação ao placebo. As demais variáveis avaliadas não evidenciaram diferença estatisticamente significante ente os dois grupos. Conclusões: O uso de probióticos representou redução nos níveis séricos de ALT na esteatose hepática na infância, indo ao encontro dos resultados obtidos por outros autores da literatura científica vigente. No que se refere às variáveis de desfecho secundário, não foi demonstrado benefício ou dano do tratamento de probióticos em relação ao placebo.

Doença de Still do adulto: um desafio diagnóstico / Adult-onset Still's disease: a diagnostic challenge

A doença de Still do adulto é uma rara condição inflamatória, cujo diagnóstico é um desafio, por se tratar de diagnóstico de exclusão, após vasta investigação. Manifesta-se com febre alta diária, amigdalite não supurativa, artrite, rash evanescente, leucocitose e hiperferritinemia. O presente caso demonstra a doença de Still do adulto e sua vasta investigação, motivando a realização de revisão bibliográfica sobre inovações na fisiopatologia, no diagnóstico e no tratamento.

Adult onset Still's disease is a rare inflammatory condition, the diagnosis of which is a challenge, because it is a diagnosis of exclusion, and demands extensive investigation. It manifests with high daily fever, nonsuppurative tonsillitis, arthritis, evanescent rash, leukocytosis, and hyperferritinemia. The present case de­monstrates adult-onset Still's disease and its extensive inves­tigation, motivating literature review on innovations of its pathophysiology, diagnosis, and treatment.

Effects of restraint stress and high-fat diet on osseointegration of titanium implants: an experimental study

Abstract This study aimed to investigate the effects of chronic restraint stress (RS) and a high-fat diet (HFD) on the osseointegration of titanium implants in a rat model. After the surgical insertion of titanium implants into the metaphysis of the tibial bone, the rats were randomly divided into four equal groups (n = 8 each): control (CNT), restraint stress (RS), high-fat diet (HFD), and restraint stress plus high fat diet (RS-HFD). CNT: Rats received no further treatment during the 92-day experimental period. RS: Stress was applied to the rats beginning from two days after the implant surgery for one hour per day for the first 30 days, two hours per day for the next 30 days, and three hours per day for the last 30 days. HFD: Rats were fed a HFD for the following 90 days starting two days after surgery. RS-HFD: Rats were fed a HFD and RS was applied to rats for the following 90 days, starting two days after surgery. At the end of the experimental period, the rats were euthanized, and the implants and surrounding bone tissues were removed for histological analysis. Statistical analysis was performed by one way ANOVA and Bonferrroni tests. There were no significant differences in the bone-implant connection levels between the groups (p > 0.05), but in the HFD and RS-HFD groups, the bone filling ratios were found to be lower compared with the controls (p < 0.05) The data analyzed in this study suggest that an HFD with or without chronic RS adversely affected bone tissue in the rats during the 90-day osseointegration period.

Outpatient analytic assessment of anorexia nervosa — the importance of venous blood gases / Avaliação laboratorial em ambulatório na anorexia nervosa: a importância da gasometria venosa

ABSTRACT Objective: To evaluate serum biochemical parameters' evolution, especially venous blood gas (VBG), in anorexia nervosa (AN), correlating with clinical parameters. Methods: Retrospective study including out-patient AN adolescents, between January 2014 and May 2017. Three evaluations were compared: t1) first consultation; t2) consultation with the lowest body mass index (BMI) z-score and t3) with the highest BMI z-score. Results: A total of 24 adolescents (87.5% females) were included, mean age of presentation of 14.9±1.7 years, onset of symptoms 6.4±3.2 months before the first visit. In t1, BMI z-score of -1.91±1.11 kg/m2 and ideal weight % of 84.3±9.2. Amenorrhea was present in 88%. In t2 the analytical alterations were: altered VBG in 100%, altered ferritin (72% elevated), altered thyroid function (53% with thyroxine decrease), dyslipidemia (31% elevation of high density lipoprotein, 25% hypercholesterolemia), elevation of urea (25%), elevation of alanine aminotransferase (14%), hypoglycemia (14%), anemia (9%). Respiratory acidosis was present in 91% in t1, 100% in t2 and 94% in t3. There was a significant decrease between t2 and t3 in mean pCO2 (57.2 versus 53.6 mmHg; p=0.009) and mean HCO3 (30.0 versus 28.8 mEq/L; p=0.023). Conclusions: Respiratory acidosis and increased ferritin were common in this group. Respiratory acidosis was the most frequent abnormality with significant pCO2 and HCO3 variation in the recovery phase. VBG should be considered in AN evaluation, once it seems to be important in assessing the severity of the disease and its subsequent follow-up.

RESUMO Objetivo: Avaliar a evolução laboratorial, particularmente da gasometria venosa, na anorexia nervosa (AN), correlacionando os achados com parâmetros clínicos. Métodos: Estudo retrospetivo com adolescentes com AN seguidos em ambulatório, entre janeiro de 2014 e maio de 2017. Foram comparadas três avaliações: (t1) primeira consulta; (t2) consulta com escore Z de índice de massa corpórea (IMC) mais baixo; e (t3) consulta com escore Z de IMC mais elevado. Resultados: Incluídos 24 adolescentes, 87,5% do sexo feminino, idade média de apresentação de 14,9±1,7 anos, início dos sintomas 6,4±3,2 meses antes da primeira consulta. Em t1, escore Z de IMC de -1,91±1,11 kg/m2 e % de peso ideal de 84,3±9,2. Tinham amenorreia 88%. Em t2 as alterações laboratoriais encontradas foram: gasometria venosa alterada em 100%, ferritina alterada (72% elevada), função tiroideia alterada (53% com diminuição da tiroxina), dislipidemia (31% com elevação de lipoproteína de alta densidade, 25% com hipercolesterolemia), elevação da ureia (25%), elevação da alanina aminotransferase (14%), hipoglicemia (14%) e anemia (9%). A acidose respiratória esteve presente em 91% em t1, 100% em t2 e 94% em t3. Verificou-se diminuição significativa entre t2 e t3 da pressão parcial de CO2 (pCO2) média (57,2 versus 53,6 mmHg; p=0,009) e HCO3 médio (30,0 versus 28,8 mEq/L; p=0,023). Conclusões: A acidose respiratória e o aumento da ferritina foram comuns nesse grupo. Acidose respiratória foi a alteração mais frequente, com variação significativa de pCO2 e HCO3 na fase de recuperação. A gasometria venosa deve ser considerada na avaliação laboratorial na AN, pois parece ser importante na avaliação da gravidade e monitorização da doença.

Hepathic, biochemical, hematological, and histological effects of the ultracavitation in rabbits livers

Abstract Purpose To collect data capable of pointing out the effects of the ultracavitation treatment on the liver of rabbits after adipose tissue application, by means of histological analyses of the liver and hematological and biochemical exams. Methods This is an experimental study with 12 albino rabbits as sample, which were divided into 3 groups and submitted to a hypercaloric diet for one month. Subsequently, subjects underwent UCV treatment: 3 minutes, 30 W, continuous mode at 100%, every 2 ERAS = 441.02 J/cm2, intensity of 10w/cm2. They were then euthanized and underwent biopsy after 24 hours. Results After 48 hours from the ultracavitation treatment, the animals' livers presented greater amount of fat infiltration if compared to the amount presented 96 hours after the treatment. However, laboratory tests showed no alterations. Values were maintained within normal parameters of cholesterol, triglycerides, liver enzymes, hemoglobin and hematocrit levels. Conclusions This study has identified that infiltrates may appear on livers after the treatment, despite high hematological and biochemical tests results. The fat infiltrates reduction 96 h after treatment suggests lower risks to animal health, if the period between applications is respected.

Application of acoustic radiation force impulse elastography combined with serum markers in Child-Pugh grading

OBJECTIVES: Acoustic radiation force impulse (ARFI) elastography, the aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), aspartate aminotransferase-to-platelet ratio index (APRI), and the fibrosis-4 (FIB-4) index are widely used to assess liver fibrosis. However, efficacies of these methods in the evaluation of hepatic functional reserve remain unclear. In this study, we investigated the relationship between ARFI elastography combined with either AAR, APRI, or FIB-4 index and Child-Pugh (CP) class for the evaluation of hepatic functional reserve in patients with chronic hepatitis B (CHB)-related cirrhosis. METHODS: The shear wave velocities of 104 patients with clinically confirmed CHB-related cirrhosis were determined using the ARFI; and clinical serum markers (e.g. ALT, AST, PLT) were used to calculate the AAR, APRI, and FIB-4 index. Cirrhosis patients were scored according to their CP class. The ARFI, AAR, APRI, and FIB-4 index were compared with the CP class. The efficacy of each indicator in diagnosis was analyzed using the receiver operating characteristic (ROC) curve and the ARFI combined with either the AAR, APRI, or FIB-4 index, which is used to predict decompensated cirrhosis. RESULTS: No significant differences were observed in gender and age among CP classes A, B, and C patients (p>0.05). The ARFI values and the AAR, APRI, and FIB-4 index of patients with CP classes A, B, and C were significantly different (p<0.05). With an increasing CP class, the ARFI, AAR, APRI, and FIB-4 values increased. The correlation between the ARFI and the CP class was stronger than that between the AAR, APRI, and FIB-4 index and the CP class. The area under the ROC curve for the diagnosis of decompensated cirrhosis using the ARFI was 0.841, which was higher than that for the AAR, APRI, and FIB-4 index. According to the area under the curve results, no significant differences were found when the ARFI was combined with either the AAR, APRI, or FIB-4 index and when the ARFI alone was used. CONCLUSIONS: The ARFI value has a strong correlation with the CP class. Therefore, ARFI elastography complements CP class in the assessment of the hepatic functional reserve in patients with CHB-related cirrhosis.

Human acute Chagas disease: changes in factor VII, activated protein C and hepatic enzymes from patients of oral outbreaks in Pará State (Brazilian Amazon)

Oral transmission of Chagas disease has been increasing in Latin American countries. The present study aimed to investigate changes in hepatic function, coagulation factor levels and parasite load in human acute Chagas disease (ACD) secondary to oral Trypanosoma cruzi transmission. Clinical and epidemiological findings of 102 infected individuals attended in the State of Pará from October 2013 to February 2016 were included. The most common symptoms were fever (98%), asthenia (83.3%), face and limb edema (80.4%), headache (74.5%) and myalgia (72.5%). The hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of 30 ACD patients were higher compared with controls, and this increase was independent of the treatment with benznidazole. Moreover, ACD individuals had higher plasma levels of activated protein C and lower levels of factor VII of the coagulation cascade. Patients with the highest parasite load had also the most increased transaminase levels. Also, ALT and AST were associated moderately (r = 0.429) and strongly (r = 0.595) with parasite load respectively. In conclusion, the present study raises the possibility that a disturbance in coagulation and hepatic function may be linked to human ACD.

Effects of restraint stress and high-fat diet on osseointegration of titanium implants: an experimental study

Abstract This study aimed to investigate the effects of chronic restraint stress (RS) and a high-fat diet (HFD) on the osseointegration of titanium implants in a rat model. After the surgical insertion of titanium implants into the metaphysis of the tibial bone, the rats were randomly divided into four equal groups (n = 8 each): control (CNT), restraint stress (RS), high-fat diet (HFD), and restraint stress plus high fat diet (RS-HFD). CNT: Rats received no further treatment during the 92-day experimental period. RS: Stress was applied to the rats beginning from two days after the implant surgery for one hour per day for the first 30 days, two hours per day for the next 30 days, and three hours per day for the last 30 days. HFD: Rats were fed a HFD for the following 90 days starting two days after surgery. RS-HFD: Rats were fed a HFD and RS was applied to rats for the following 90 days, starting two days after surgery. At the end of the experimental period, the rats were euthanized, and the implants and surrounding bone tissues were removed for histological analysis. Statistical analysis was performed by one way ANOVA and Bonferrroni tests. There were no significant differences in the bone-implant connection levels between the groups (p > 0.05), but in the HFD and RS-HFD groups, the bone filling ratios were found to be lower compared with the controls (p < 0.05) The data analyzed in this study suggest that an HFD with or without chronic RS adversely affected bone tissue in the rats during the 90-day osseointegration period.

High-Lard and High-Cholesterol Diet, but not High-Lard Diet, Leads to Metabolic Disorders in a Modified Dyslipidemia Model / Dieta Rica em Banha e Colesterol, mas não Dieta Rica em Banha, Leva a Distúrbios Metabólicos em um Modelo Modificado de Dislipidemia

Abstract Background: In view of the increased global prevalence of cardiovascular and hepatic diseases, the diet lipid content and its relationship with the accumulation of fat in hepatocytes have been investigated as key factors in preventing these diseases. Objective: To evaluate the metabolic effects of a high-lard diet supplemented or not with cholesterol on a modified dyslipidemia model. Methods: We divided 24 adult male Wistar rats into three groups: standard diet (STD - 4% lipids), high-lard diet (HLD - 21% lard), and high-lard and high-cholesterol diet (HL/HCD - 20% lard, 1% cholesterol, 0.1% cholic acid). After six weeks of treatment, blood and liver were collected for biochemical (serum lipid profile and liver enzymes) and morphological analyses. Statistical analysis included one-way analysis of variance (ANOVA), followed by Tukey test for mean comparisons, and a 5% probability was considered statistically significant. Results: Animals fed HL/HCD showed increased total cholesterol, triacylglycerol, LDL-c, non-HDL-c, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) serum levels compared to those fed STD. In addition, the HL/HCD animals presented higher relative liver weight, with moderate macrovesicular hepatic steatosis and inflammatory infiltrate. Conclusion: A high-fat diet with lard (20%) and cholesterol (1%) triggered dyslipidemia with severe liver damage in rats in a shorter experimental time than the previously reported models. The high-lard diet without supplementation of cholesterol led to body weight gain, but not to dyslipidemia.

Resumo Fundamento: Tendo em vista o aumento da prevalência global de doenças cardiovasculares e hepáticas, o conteúdo lipídico da dieta e sua relação com o acúmulo de gordura nos hepatócitos têm sido investigados como fatores-chave na prevenção dessas doenças. Objetivo: Avaliar os efeitos metabólicos de uma dieta rica em banha suplementada com colesterol ou não, em um modelo modificado de dislipidemia. Métodos: Foram divididos 24 ratos Wistar machos adultos em três grupos: dieta padrão (DP - 4% de lipídios), dieta rica em banha (DRB - 21% de banha) e dieta rica em banha e colesterol (DRB/RC - 20% de banha, 1% de colesterol e 0,1% de ácido cólico). Após seis semanas de tratamento, o sangue e o fígado foram coletados para análises bioquímicas (perfil lipídico sérico e enzimas hepáticas) e morfológicas. A análise estatística incluiu análise de variância unidirecional (ANOVA), seguida do teste de Tukey para comparações de médias. Uma probabilidade de 5% foi considerada estatisticamente significativa. Resultados: Animais alimentados com DRB/RC apresentaram um aumento nos níveis séricos de colesterol total, triacilglicerol, LDL-c, não-HDL-c, alanina aminotransferase (ALT) e aspartato aminotransferase (AST) em comparação com aqueles alimentados com DP. Além disso, os animais tratados com DRB/RC apresentaram um peso relativo do fígado maior, com esteatose hepática macrovesicular moderada e infiltrado inflamatório. Conclusão: Uma dieta rica em gordura com banha (20%) e colesterol (1%) desencadeou dislipidemia com danos graves ao fígado em ratos em um tempo experimental menor do que os modelos previamente relatados. A dieta rica em banha sem suplementação de colesterol levou ao ganho de peso corporal, mas não à dislipidemia.

Eficácia hepatoprotetora do extrato metanólico de Indigofera suffruticosa (Mill) em lesão hepática induzido por paracetamol em camundongos / Hepatoprotective efficacy of methanolic extract of indigofera suffruticosa (mill) on paracetamol-induced liver damage in mice

ABSTRACT BACKGROUND: Indigofera suffruticosa Mill (Fabaceae) is abundant in northeastern Brazil and popularly used in the treatment of infectious and inflammatory processes. Several biological properties, such as anti-inflammatory, anticancer, antitumor, hepatoprotective and low toxicity, are reported for this plant. OBJECTIVE: This study investigated hepatoprotective activity and the antioxidant effect of methanolic extract of I. suffruticosa leaves (MEIS) on Swiss albino mice submitted to experimental models of acetaminophen-induced liver injury. METHODS: MEIS (50 mg/kg; p.o.) was standardized according to the LD50 and its hepatoprotective property on Swiss albino mice evaluated during a 7-day period. On the eighth day, the acetaminophen-induced hepatic injury was performed. Histomorphometric analysis of liver tissue, antioxidant activity and serum levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT) and bilirubin were measured. RESULTS: MEIS (50 mg/kg; p.o.) restored serum enzyme levels and results were close to those of positive control (silymarin) when compared to the negative control. Histopathological and histomorphometric analyzes confirmed MEIS hepatoprotective activity, showing reorganization of structural units of cells, nuclei and sinusoidal capillaries of hepatocytes, reducing the damage on liver tissue and increasing organ regeneration rate. MEIS showed high antioxidant potential at concentrations of 1000 and 500 µg/mL. CONCLUSION: This study suggests that MEIS has hepatoprotective activity and high antioxidant potential.

RESUMO CONTEXTO: Indigofera suffruticosa Mill (Fabaceae) é abundante no nordeste do Brasil e popularmente utilizada no tratamento de processos infecciosos e inflamatórios. Várias propriedades biológicas, como anti-inflamatório, anticâncer, antitumoral, hepatoprotetor e baixa toxicidade, são relatadas para esta planta. OBJETIVO: Este estudo investigou a atividade hepatoprotetora e o efeito antioxidante do extrato metanólico de folhas de I. suffruticosa (MEIS) em camundongos albinos suíços submetidos a modelos experimentais de lesão hepática induzida por paracetamol. MÉTODOS: O MEIS na dose de 50 mg/kg (via oral) foi padronizado de acordo com a LD50 e sua propriedade hepatoprotetora em camundongos albinos Swiss avaliados durante um período de sete dias. No oitavo dia, a lesão hepática foi induzida por paracetamol em todos grupos pre-tratados. Foram medidos os níveis sericos enzimaticos, alanina aminotransferase, aspartato aminotransferase e bilirrubina, análise histomorfométrica do tecido hepático e atividade antioxidante. RESULTADOS: O MEIS restaurou os níveis séricos de enzimas e os resultados foram próximos aos do controle positivo (silimarina) quando comparados ao controle negativo. As análises histopatológicas e histomorfométricas confirmaram a atividade hepatoprotetora do MEIS, mostrando reorganização das unidades estruturais das células, núcleos e capilares sinusoidais dos hepatócitos, reduzindo os danos no tecido hepático e aumentando a taxa de regeneração de órgãos. O MEIS apresentou alto potencial antioxidante nas concentrações de 1000 e 500 µg/mL. CONCLUSÃO: Este estudo sugere que I. suffruticosa tem atividade hepatoprotetora e alto potencial antioxidante.

Evaluation of frequency of autoimmune hepatitis autoantibodies in children with type 1 diabetes / Frecuencia de anticuerpos de hepatitis autoinmune en niños con diabetes tipo I

Background: Diabetes mellitus type 1 (T1DM) is one of the childhood diseases with growing prevalence. Various accompanying autoimmune diseases were seen with type 1 diabetes. The most common autoimmune diseases with T1DM are autoimmune thyroiditis and celiac disease. In some reports, autoimmune hepatitis has been reported in association with DM-1. Objectives: The aim of this study was to evaluate autoimmune hepatitis autoantibodies in children with T1DM. Materials and methods: In this crosssectional study, 202 children with T1DM were evaluated (47.5% were males and 52.5% were girls). Liver enzymes, autoimmune hepatitis related autoantibodies such as anti-nuclear antibodies (ANA), anti-smooth muscle (ASMA) and anti liver and kidney microsomal antibodies (LKM-1) were measured. Liver ultrasound was done for participants and biopsy of liver was taken for children with increased echogenicity of the liver, hepatomegaly or elevated liver enzymes. Results analyzed by statistical software spss-16, Descriptive statistics and chi-square test, paired T-TEST. Level of less than 5% was considered statistically significant. Results: In 6 patients ANA and in 4 patients (2%) ASMA was positive,1 patient was ASMA positive but ANA negative. None of the patients were Anti LKM-1 positive. 3 patients had positive ANA and ASMA, and increased liver echogenicity on ultrasound simultaneously. Histological evaluation was showed that 2 patients had findings in favor of autoimmune hepatitis. Conclusion: Auto antibodies were positive in 10 cases. ANA was positive in 6 (2.97%) of all cases. ASMA was positive in 4 (1.98%) cases. Increased echogenicity was found in 3 cases. Histological evaluation showed 2 patients had biopsy confirmed autoimmune hepatitis. AIH-2 was not seen among our cases.

Antecedentes: La diabetes mellitus tipo 1 (DM1) es una de las enfermedades infantiles con mayor prevalencia. Se observaron varias enfermedades autoinmunes acompañantes con diabetes tipo 1. Las enfermedades autoinmunes más comunes con DM1 son la tiroiditis autoinmune y la enfermedad celíaca. En algunos reportes, se ha encontrado hepatitis autoinmune en asociación con DM-1. Objetivos: El objetivo de este estudio fue evaluar los autoanticuerpos de hepatitis autoinmunes en niños con DM1. Materiales y métodos: En este estudio transversal, se evaluaron 202 niños con DM1 (47,5% eran hombres y 52,5% eran niñas). Se midieron las enzimas hepáticas, los autoanticuerpos autoinmunes relacionados con la hepatitis, como los anticuerpos antinucleares (ANA), el músculo liso (ASMA) y los anticuerpos microsomales hepáticos y renales (LKM-1). Se realizó una ecografía hepática para los participantes y se tomó una biopsia del hígado para niños con mayor ecogenicidad del hígado, hepatomegalia o enzimas hepáticas elevadas. Los resultados fueron analizados por el software estadístico spss-16 usando estadística descriptiva y prueba de chi-cuadrado, T-TEST pareado. Se consideró estadísticamente significativo un nivel menor del 5%. Resultados: En 6 pacientes con ANA y en 4 pacientes (2%) ASMA fue positiva, 1 paciente fue ASMA positiva pero ANA negativa. Ninguno de los pacientes fue anti LKM-1 positivo. 3 pacientes tuvieron ANA y ASMA positivas, y aumentaron la ecogenicidad hepática en la ecografía simultáneamente. La evaluación histológica mostró que 2 pacientes tenían hallazgos a favor de la hepatitis autoinmune. Conclusión: Los autoanticuerpos fueron positivos en 10 casos. ANA fue positivo en 6 (2,97%) de todos los casos. La ASMA fue positiva en 4 (1,98%) casos. Se encontró mayor ecogenicidad en 3 casos. La evaluación histológica mostró que 2 pacientes tenían biopsia confirmada de hepatitis autoinmune. AIH-2 no fue visto entre nuestros casos.

Lysosomal acid lipase deficiency in Brazilian children: a case series / Deficiência de lipase ácida lisossomal em crianças brasileiras: casuística

Abstract Objective: To describe the demographic, clinical, laboratory and molecular characteristics of patients with lysosomal acid lipase deficiency. Methods: A retrospective review of the medical records of children with the disease. Results: Seven children with lysosomal acid lipase deficiency (5 male; 2 female); 6 were mixed race, and 1 was black. The mean ages at the first onset of symptoms and at diagnosis were 5.0 years (4 months to 9 years) and 6.9 years (3-10 years), respectively. Symptom manifestations at onset were: 3 patients had abdominal pain, one had bone/joint pain due to rickets, and 1 had chronic diarrhea and respiratory insufficiency due to interstitial pneumonitis. One was asymptomatic, and clinical suspicion arose due to hepatomegaly. Six patients had hepatomegaly, and none had splenomegaly. Two patients were siblings. Enzymatic assay and molecular analysis confirmed the diagnoses. Genetic analysis revealed a rare pathogenic variant (p.L89P) in three patients, described only once in medical literature and never described in Brazil. None of those patients were related to each other. Lysosomal acid lipase deficiency was previously described as an autosomal recessive disease, but three patients were heterozygous and undoubtedly had the disease (low enzyme activity, suggestive lab findings and clinical symptoms). Conclusion: This case series supports that lysosomal acid lipase deficiency can present with highly heterogeneous signs and symptoms among patients, but it should be considered in children presenting with gastrointestinal symptoms associated with dyslipidemia. We describe a rare variant in three non-related patients that may suggest a Brazilian genotype for lysosomal acid lipase deficiency.

Resumo: Objetivo: Descrever as características demográficas, clínicas, laboratoriais e moleculares de pacientes com deficiência de lipase ácida lisossomal. Métodos: Análise retrospectiva dos prontuários médicos de crianças com a deficiência de lipase ácida lisossomal. Resultados: Sete crianças com deficiência de lipase ácida lisossomal (5 M:2F); seis eram pardas e uma negra. As faixas etárias no início dos sintomas e no diagnóstico foram 5 anos (4 meses a 9 anos) e 6,9 anos (3 a 10 anos), respectivamente. As manifestações dos sintomas no início foram as que seguem: três pacientes apresentaram dor abdominal, um apresentou dor nos ossos/articulações devido a raquitismo e um apresentou diarreia crônica e insuficiência respiratória devido à pneumonite intersticial. Os outros não apresentaram sintomas e a suspeita clínica surgiu devido à hepatomegalia. Seis pacientes apresentaram hepatomegalia e um apresentou esplenomegalia. Dois pacientes eram irmãos. O ensaio enzimético e a análise molecular confirmaram os diagnósticos. A análise genética revelou uma variante patogênica rara (p.L89P) em três pacientes, descrita uma única vez na literatura médica e nunca descrita no Brasil. Nenhum desses pacientes tinha parentesco com os outros. A deficiência de lipase ácida lisossomal foi anteriormente descrita como uma doença recessiva autossômica, porém três pacientes eram heterozigotos e, sem dúvida, apresentaram a doença (atividade enzimática baixa, achados laboratoriais sugestivos e sintomas clínicos). Conclusão: Esta casuística afirma que a deficiência de lipase ácida lisossomal pode se manifestar com sinais e sintomas altamente heterogêneos entre os pacientes, porém deve ser considerada em crianças que apresentam sintomas gastrointestinais associados à dislipidemia. Descrevemos uma variante rara em três pacientes não relacionados que pode sugerir um genótipo brasileiro para deficiência de lipase ácida lisossomal.

Evaluation of the use of tacrolimus ointment for the prevention of hypertrophic scars in experimental model

Abstract BACKGROUND: Tacrolimus, for its activity on modulation of collagen production and fibroblast activity, may have a role in the prevention of hypertrophic scars. OBJECTIVES: Evaluate macroscopic, microscopic, metabolic, laboratory effects and side effects of the use of topical tacrolimus ointment, in different concentrations, in the prevention of hypertrophic scars. METHODS: Twenty-two rabbits were submitted to the excision of 2 fragments of 1 cm of each ear, 4 cm apart, down to cartilage. The left ear of the animals was standardized as control and Vaseline applied twice a day. The right ear received tacrolimus ointment, at concentrations of 0.1% on the upper wound and 0.03% on the lower wound, also applied twice a day. Macroscopic, microscopic, laboratory criteria and the animals' weight were evaluated after 30 days of the experiment. RESULTS: Wounds treated with tacrolimus, at concentrations of 0.1% and 0.03%, when compared to control, showed a lower average degree of thickening (p = 0.048 and p <0.001, respectively). The average of scar thickness and lymphocyte, neutrophil and eosinophil concentrations are lower in the treated wounds compared to the control (p <0.001, p=0.022, p=0.007, p=0.044, respectively). The mean concentration of lymphocytes is lower in wounds treated with a higher concentration of the drug (p=0.01). STUDY LIMITATIONS: experiment lasted only 30 days. CONCLUSIONS: Tacrolimus at the 2 concentrations evaluated reduced the severity of inflammatory changes and positively altered the macroscopic aspect of the scar in the short term. Its use was shown to be safe, with no evidence of systemic or local adverse effects.

Fasting insulin and alanine amino transferase, but not FGF21, were independent parameters related with irisin increment after intensive aerobic exercising

Abstract Background Irisin is a protein cleaved from fibronectin type III domain-containing protein 5 and has been implicated in the beneficial effects of exercise. However, it is unknown which factors contribute to irisin increment after intensive exercising in humans. This study aimed to assess independent factors related with serum irisin after 2 weeks of supervised physical activity in young sedentary healthy women. Design and Methods We developed a comparative, interventional, longitudinal, and prospective study at a third-level specialty health center. Between March 2010 and August 2011, 82 sedentary young adult women, without chronic diseases or regular medical treatments, were recruited. A total of 38 women fulfilled selection criteria, and irisin concentrations were quantified before and after the intervention. Independent factors related with irisin increment were evaluated according to mild to moderate and vigorous intensity of physical activity. A supervised treadmill exercise test following the Bruce’s protocol was conducted from Monday to Friday during 2 weeks. In addition, anthropometric measurements were taken, and fibroblast growth factor 21 (FGF21), glucose, insulin, and liver transaminases were measured. Results Intensity of exercising was directly related to irisin (p = 0.02) and FGF21 (p = 0.01) serum levels. However, an independent and significant relationship between FGF21 and irisin was not confirmed. A novel association was found between alanine aminotransferase (ALT) and irisin, showing a positive and significant correlation (r = 0.37, p = 0.02). The association was particularly strong with higher intensity of aerobic exercising (r = 0.64, p = 0.01). Linear regression model adjusted for glucose and body mass index confirmed an independent association between ALT and irisin and also between insulin and irisin (adjusted R² = 0.12, p = 0.04). Such association increased after grouping in moderate to vigorous physical activity intensity (adjusted R² = 0.46, F = 4.7, p = 0.03). Conclusions Serum irisin and FGF21 levels significantly increased after 2 weeks of supervised physical activity. However, only fasting insulin and ALT, but not FGF21, were independent parameters explaining irisin increment, mainly after moderate to vigorous exercising.

Yellow fever: profile of cases and factors associated with death in a hospital in the State of Rio de Janeiro, 2017-2018 / Febre amarela: perfil dos casos e fatores associados ao óbito em hospital referência no estado do Rio de Janeiro, 2017-2018

ABSTRACT OBJECTIVE Describe the clinical and epidemiological profile of confirmed cases of yellow fever whose patients were hospitalized in a general hospital for infectious diseases in the State of Rio de Janeiro, Brazil, from March 11, 2017 to June 15, 2018, during a recent outbreak and factors associated with death. METHODS This is a retrospective observational study with analysis of secondary databases of local epidemiological surveillance system, and complementary data collection from epidemiological investigation records and clinical records. Study variables included demographic, epidemiological, clinical, and laboratory data. A descriptive statistical analysis and a bivariate and multivariate analysis by logistic regression were performed to analyze factors associated with death. RESULTS Fifty-two patients diagnosed with yellow fever were hospitalized, 86.5% male patients, median age 49.5 years, 40.4% rural workers. The most frequent signs and symptoms were fever (90.4%), jaundice (86.5%), nausea and/or vomiting (69.2%), changes in renal excretion (53.8%), bleeding (50%), and abdominal pain (48.1%), with comorbidity in 38.5% of all cases. The lethality rate was 40.4%. Factors significantly associated with a higher chance of death in the bivariate analysis were: bleeding, changes in renal excretion, and maximum values of direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine. In the multivariate analysis by logistic regression, only changes in renal excretion and ALT remained significant predictors of higher chance of death. A threshold effect was also observed for AST. The cutoff points identified as high risk for death were ALT > 4,000 U/L and AST > 6,000 U/L. CONCLUSIONS This study contributed to the knowledge on the profile of confirmed cases of high severity yellow fever. The main factors associated with death were changes in renal excretion and elevated serum transaminases, especially ALT. High lethality emphasizes the need for early diagnosis and treatment, and the importance of increasing vaccination coverage.

RESUMO OBJETIVO Descrever o perfil clínico-epidemiológico dos casos confirmados de febre amarela internados em hospital geral de referência para doenças infecciosas no estado do Rio de Janeiro, Brasil, de 11 de março de 2017 a 15 de junho de 2018, durante recente surto e fatores associados ao óbito. MÉTODOS Estudo observacional retrospectivo, com análise de bases de dados secundários da vigilância epidemiológica local e coleta complementar de dados nas fichas de investigação epidemiológica e prontuários clínicos. As variáveis analisadas incluíram dados demográficos, epidemiológicos, clínicos e laboratoriais. Foi conduzida análise estatística descritiva bivariada e múltipla por regressão logística para estudo de fatores associados ao óbito. RESULTADOS Foram internados 52 casos confirmados, 86,5% deles homens, com mediana de idade de 49,5 anos e 40,4% trabalhadores rurais. Os sinais e sintomas mais frequentes foram: febre (90,4%), icterícia (86,5%), náuseas e/ou vômitos (69,2%), alterações de excreção renal (53,8%), hemorragias (50%) e dor abdominal (48,1%), com comorbidade em 38,5% dos casos. A letalidade foi de 40,4%. Os fatores associados significativamente à maior chance de óbito na análise bivariada foram: hemorragia, alterações de excreção renal e valores máximos de bilirrubina direta, aspartato aminotransferase (AST), alanina aminotransferase (ALT), ureia e creatinina. Na análise múltipla por regressão logística, apenas alterações de excreção renal e ALT permaneceram como preditores significativos de maior chance de óbito. Observou-se ainda efeito limítrofe para AST. Os pontos de corte identificados como de alto risco para óbito foram ALT > 4.000 U/L e AST > 6.000 U/L. CONCLUSÕES O estudo contribuiu para o conhecimento do perfil de casos confirmados de febre amarela com gravidade alta. Os principais fatores associados ao óbito foram a alteração da excreção renal e a elevação sérica de transaminases, sobretudo a ALT. A letalidade elevada reforça a necessidade de diagnóstico e tratamento precoces, e a importância do incremento da cobertura vacinal.

Effect of sevoflurane pretreatment in relieving liver ischemia/reperfusion-induced pulmonary and hepatic injury

Abstract Purpose To investigate the effect of sevoflurane preconditioning on ischemia/reperfusion (I/R)-induced pulmonary/hepatic injury Methods Fifty-one Wistar rats were randomly grouped into sham, I/R, and sevoflurane groups. After reperfusion, the structural change of the lung was measured by Smith score, the wet and dry weights (W/D) were determined, malondialdehyde (MDA) myeloperoxidase (MPO) content was determined colorimetrically and by fluorescence, respectively, and matrix metalloprotein-9 (MMP-9) mRNA was quantified by RT-PCR. Biopsy and morphological analyses were performed on liver tissue, activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined, and tumor necrosis factor-alpha (TNF-α) level was determined. Results The sham group showed no changes in tissue structure. Structural lesions in the sevoflurane and I/R groups were mild and severe, respectively. Smith score, W/D, MDA, MPO, and MMP mRNA showed the same trend, and were increased in the I/R group and recovered in the sevoflurane group, compared with the sham group (both P<0.05). AST and ALT were significantly increased compared to the sham group (AST: 655±52.06 vs . 29±9.30 U/L; ALT: 693±75.56 vs . 37±6.71 U/L; P<0.05). In the sevoflurane group, AST and ALT levels were significantly decreased (464±47.71 and 516±78.84 U/L; P<0.001). TNF-α presented similar results. Conclusion The protection of lung and liver by sevoflurane may be mediated by inhibited leukocyte recruitment and MMP-9 secretion.

Pretreatment of hepatetctomized rats with Coleus forskohlii did not interfere with the course of hepatic hyperplasia

Abstract Purpose Coleus forskohlii Briq., a medicinal plant originally from India, has been indicated against heart disease, expiratory disorders, convulsions, and hepatic changes, among others. In view of the broad pharmacological potential of the plant and the scarce information about its effects, the objective of the present study was to investigate the effect of its use for pretreatment of partially hepatectomized rats. Methods The animals were divided into two experimental groups: Control (CG) receiving physiological saline for 10 days before partial hepatetctomy, and Treated (TG) receiving 40 mg Coleus forskohlii/kg/day for 10 days before partial hepatectomy. The treatments were performed by gastric gavage. After the surgical procedure, treatment was continued according to the following groups: CG 24 h, CG 48 h, TG 24 h, and TG 48 hs, and liver tissue and intracardiac blood samples were obtained for histological and biochemical analysis, respectively. Results No significant differences were observed in mitotic or apoptotic index or in the concentrations of the enzymes AST, ALT and alkaline phosphatase, and no areas of fibrosis were detected. Conclusion Treatment with Coleus forskohlii did not interfere with the course of hepatic hyperplasia.

IgG1 and IgG4 antibodies against core and NS3 antigens of hepatitis C virus

Abstract INTRODUCTION: IgG subclasses involved in the immune response to hepatitis C virus (HCV) antigens have been rarely studied. We investigated the immune response mediated by IgG1 and IgG4 antibodies against the recombinant core and NS3 antigens in patients with chronic hepatitis C. METHODS: Sixty patients infected with HCV genotype 1 without antiviral treatment and 60 healthy subjects participated in the study. Serum levels of alanine aminotransferase, HCV viremia, and the presence of cryoglobulinemia and liver fibrosis were determined. We investigated the serum IgG1 and IgG4 antibodies against recombinant HCV core and NS3 non-structural protein antigens using amplified indirect ELISA. RESULTS: Anti-core and anti-NS3 IgG1 antibodies were detected in 33/60 (55%) and 46/60 (77%) patients, respectively, whereas only two healthy control samples reacted with an antigen (NS3). Anti-core IgG4 antibodies were not detected in either group, while 30/60 (50%) patients had anti-NS3 IgG4 antibodies. Even though there were higher levels of anti-NS3 IgG4 antibodies in patients with low viremia (< 8 × 105 IU/mL), IgG1 and IgG4 antibody levels did not correlate with ALT levels, the presence of cryoglobulinemia, or degree of hepatic fibrosis. High production of anti-core and anti-NS3 IgG1 antibodies was observed in chronic hepatitis C patients. In contrast, IgG4 antibodies seemed to only be produced against the NS3 non-structural antigen and appeared to be involved in viremia control. CONCLUSIONS: IgG1 antibodies against structural and non-structural antigens can be detected in chronic hepatitis C, while IgG4 antibodies seem to be selectively stimulated by non-structural HCV proteins, such as the NS3 antigen.

Observation of the effect of bone marrow mesenchymal stem cell transplantation by different interventions on cirrhotic rats

Bone marrow mesenchymal stem cells (BMSCs) transplantation has attracted attention for the treatment of liver cirrhosis and end-stage liver diseases. Therefore, in this study, we evaluated the effect of different methods of BMSCs transplantation in the treatment of liver cirrhosis in rats. Seventy-two male Sprague-Dawley rats were divided into 7 groups: 10 were used to extract BMSCs, 10 were used as normal group, and the remaining 52 rats were randomly divided into five groups for testing: control group, BMSCs group, BMSCs+granulocyte colony-stimulating factor (G-CSF) group, and BMSCs+Jisheng Shenqi decoction (JSSQ) group. After the end of the intervention course, liver tissue sections of rats were subjected to hematoxylin and eosin (H&E) and Masson staining, and pathological grades were scored. Liver function [aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB)] and hepatic fibrosis markers [hyaluronidase (HA), laminin (LN), type III procollagen (PCIII), type IV collagen (CIV)] were measured. BMSCs+JSSQ group had the best effect of reducing ALT and increasing ALB after intervention therapy (P<0.05). The reducing pathological scores and LN, PCIII, CIV of BMSCs+G-CSF group and BMSCs+JSSQ group after intervention therapy were significant, but there was no significant difference between the two groups (P>0.05). The effect of JSSQ on improving stem cell transplantation in rats with liver cirrhosis was confirmed. JSSQ combined with BMSCs could significantly improve liver function and liver pathology scores of rats with liver cirrhosis.