Effect of atorvastatin and diet on non-alcoholic fatty liver disease activity score in hyperlipidemic chickens.

Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), which includes from simple steatosis and steatohepatitis, to the most severe cirrhosis and carcinoma, which develops in the absence of excessive alcohol intake. NAFLD is the most common liver disorder in affluent societies. There is no proven treatment for NAFLD/NASH. One of the most frequent adverse effects of statins is an increase in hepatic aminotransferases. Studies that evaluate if the benefits of statins overcome the risks in NASH are lacking. The present study was conceived to explore the effect of both atorvastatin and diet on regression of steatohepatitis, using a chicken experimental model induced by a hyperlipidemic diet (HD). Plasma lipid levels, liver enzymes and hepatic histopathology, as well as image analysis were performed to determine changes in liver lipid deposits and inflammatory infiltration. Features of steatosis, cell-ballooning, and inflammation were scored to obtain the NAFLD activity score (NAS). A severe level of steatosis was found in animals fed on HD. Atorvastatin treated groups showed smaller size of lipid deposits and a lower level of inflammation than non-treated groups. Atorvastatin therapy induced a significant reduction of hepatocellular damage, even though in the animals which continuously received a hyperlipidemic diet. The combination of atorvastatin therapy and a standard diet produced the lowest decrease of NAS. Our results show that atorvastatin therapy not only decreased plasmatic levels of cholesterol and triglycerides, but also induced a reduction of liver steatosis, inflammation and hepatocellular damage, without increasing plasmatic aminotransferase levels.

[Pancreatic tuberculosis with duodenal fistula]. / Tuberculosis pancreática con fistulización a duodeno.

Tuberculosis is a common infection worldwide. In developed countries, the incidence of this disease was low until a few years ago. However, due to the rise in immigration and HIV infection, the frequency of tuberculosis has recently shown a marked increase. Although the most frequent location of tuberculosis infection continues to be respiratory, infection in other sites, such as musculoskeletal, genitourinary, neurological and abdominal areas, has recently become more common. Abdominal infection, the most frequently described extrapulmonary localization, commonly affects the spleen, liver, ileocecal region, peritoneum, and regional lymph nodes. Tuberculosis of the pancreas is considered a rare entity.

Tuberculosis pancreática con fistulización a duodeno / Pancreatic tuberculosis with duodenal fistula

La tuberculosis es una entidad frecuente en todo el mundo. En los países desarrollados se describía hasta hace unos años un descenso en su incidencia, pero debido al aumento de flujos migratorios y a la aparición del sida, se ha detectado un notable aumento en su frecuencia en los últimos tiempos. A pesar de que la localización clásica con afectación pulmonar continúa siendo la forma de presentación más comunicada, se ha descrito un incremento en el diagnóstico en otras localizaciones. La afectación de otros órganos y aparatos, como el sistema muscular esquelético, el genitourinario, el neurológico o el abdominal, ha dejado de ser infrecuente. La abdominal es una localización extrapulmonar cada vez más frecuente, zona en la que se ha descrito una afectación de diversas estructuras: cadenas linfáticas mesentéricas, intestino delgado, peritoneo, hígado y bazo. La afectación pancreática es una entidad muy infrecuente

Tuberculosis is a common infection worldwide. In developed countries, the incidence of this disease was low until a few years ago. However, due to the rise in immigration and HIV infection, the frequency of tuberculosis has recently shown a marked increase. Although the most frequent location of tuberculosis infection continues to be respiratory, infection in other sites, such as musculoskeletal, genitourinary, neurological and abdominal areas, has recently become more common. Abdominal infection, the most frequently described extrapulmonary localization, commonly affects the spleen, liver, ileocecal region, peritoneum, and regional lymph nodes. Tuberculosis of the pancreas is considered a rare entity (AU)

Efecto de la atorvastatina sobre la progresión y regresión de los depósitos grasos renales en un modelo experimental / Effect of atorvastatin on progression/regression of renal lipid accumulation in an experimental model

Introducción. Hay evidencias de la relación entre la arteriosclerosis y la enfermedad renal progresiva. Sin embargo, son escasos los estudios en humanos o animales en que se utilicen estatinas para valorar sus efectos sobre la lesión renal. Objetivos. El objetivo de este trabajo es estudiar a escala histológica el efecto de la atorvastatina sobre los fenómenos de progresión y regresión de los depósitos grasos en el riñón en un modelo experimental. Material y método. Para la realización de los protocolos experimentales se utilizaron 100 pollos White-Leghorn, sometidos a una dieta hiperlipémica en la fase de inducción y a diversos protocolos de dieta normal/dieta hiperlipémica y tratamiento o no con atorvastatina en la fase de intervención. Se realizó la valoración de la grasa renal mediante técnicas histológicas y análisis de imagen. Resultados. En el grupo control sano no se observó la existencia de depósitos grasos, mientras que el grupo aterogénico presentó grandes depósitos grasos. El grupo de regresión e intervención con atorvastatina presentó una menor presencia de grasa, lo que supuso una diferencia significativa con todos los grupos. También en el caso de este grupo, se encontró que el diámetro de la acumulación grasa es significativamente menor respecto al resto de los grupos. Conclusiones. Nuestro modelo experimental es, para el estudio del riñón graso, un modelo homogéneo y de fácil manejo. La retirada de la dieta grasa y la administración simultánea de atorvastatina da lugar a los índices más bajos de depósitos grasos renales. La retirada por sí sola de la dieta no produce efectos tan marcados. Del estudio de diferentes parámetros se deduce que la atorvastatina acelera la regresión y frena la progresión de las acumulaciones grasas renales (AU)

Introduction. There is evidence of a relationship between atherosclerosis and progressive kidney disease. However, information on the role of statins on kidney disease in humans and animal models is lacking. Objectives. To analyze the effect of atorvastatin on progression/regression of renal lipid accumulation in an experimental model using histological analysis. Material and method. We used 100 White-Leghorn chickens fed with a hyperlipemic diet (induction stage), followed by an interventional stage, in which the animals were fed a normal or hyperlipemic diet and administered atorvastatin or placebo. Assessment of renal lipid accumulation was made by histologic and imaging analyses. Results. In the healthy control group, no intracellular renal fat deposits or accumulations were found. The atherogenic group showed substantial lipid accumulations. The intervention group with suspension of the hyperlipemic diet and atorvastatin administration showed significant differences with the remaining groups, presenting the lowest fat accumulation. This group also showed significantly lower fat accumulation diameter with respect to the remaining groups. Conclusions. Our experimental model was useful and suitable for the study of renal fat accumulation. Hyperlipemic diet suspension and simultaneous atorvastatin therapy led to the lowest renal fat accumulation. Hyperlipemic diet suspension alone produced less pronounced results. The parameters studied indicate that atorvastatin was effective in accelerating regression of renal fat accumulation and in decreasing its progression (AU)

Intracellular retention of hepatic serpins caused by severe hyperlipidemia.

BACKGROUND: High levels of circulating lipids contribute to both the development of non-alcoholic liver steatosis (NALS) and peripheral arterial disease, leading to increased thrombotic risk. However, the effects of hyperlipidemia on hepatic proteins have barely been studied. Antithrombin is a hepatic serpin with anticoagulant and anti-inflammatory roles. The conformational flexibility of antithrombin renders it susceptible to both, genetic and posttranslational modifications. Thus, mutations and environmental factors have been shown to alter this molecule. METHODS: We used a chick model to assess the effects of hyperlipidemic diets (HD) on this conformationally sensitive molecule. We determined antithrombin activity in plasma and evaluated the histological and immunohistological features of livers from these animals. RESULTS: A HD for 6 months led to a significant intrahepatic retention and aggregation of antithrombin, which correlated with hepatic steatosis, as revealed by immunohistological analysis. Accordingly, a decrease in circulating antithrombin activity (48.71 +/- 6.35%) was observed. Other hepatic proteins, including heparin cofactor II, another anticoagulant serpin, also accumulated intracellularly. Atorvastatin and reversion to a normal diet after 3 months partially protected livers from these deleterious effects. CONCLUSIONS: Our results support that hyperlipidemia-induced NALS causes a significant intracellular aggregation of hemostatic serpins in liver, which determines a decrease in their circulating levels.