Colestasis intrahepática drepanocítica a propósito de un casoy revisión de la literatura / Sickle cell intrahepatic cholestasis regarding a case and reviewof the literature

La enfermedad de células falciformes (ECF) o anemia drepanocítica, es el trastorno hereditario más frecuente en los glóbulos rojos, y la enfermedad con más complicaciones en diferentes órganos, lo que provoca múltiples presentaciones de una misma enfermedad., se hace revisión literatura sobre ECF y colestasis intrahepática drepanocítica, y se describe un caso presentado en el Hospital General y de Especialidades Nuestra Señora de la Altagracia de Higüey Republica Dominicana en el año 2022. Es un varón de 24 años, con diagnóstico de ECF, que se complicó con una colestasis intrahepática drepanocítica muy severa que se manejó con hemodiálisis. El objetivo de publicar este caso es revisar la información respecto a la incidencia y la morbimortalidad de esta complicación, teniendo en cuenta que fue tratado por un equipo multidisciplinario usando la hemodiálisis como alternativa terapéutica(AU)

Sickle cell disease (SCD) or sickle cell anemia is the most common hereditary disorder in red blood cells, and the disease with the most complications in different organs, which causes multiple presentations of the same disease. Literature review on SCD is made and sickle cell intrahepatic cholestasis,and a case presented at the Hospital General y de Especialidades Nuestra Señora de la Altagracia de Higüey in the Dominican Republic in 2022 is described. Very severe sickle cell intrahepatic disease that was managed with hemodialysis. The purpose of publishing this case is to review the information regarding the incidence and morbidity and mortality of this complication,taking into account that it was treated by a multidisciplinary team using hemodialysis as a therapeutic alternative(AU)

Expert consensus on the diagnosis and treatment of intrahepatic cholestasis (2021 edition) / 中华肝脏病杂志

Intrahepatic cholestasis is a clinical syndrome due to the defect of bile acid synthesis, abnormal bile excretion, and mechanical or functional disturbance of intrahepatic bile flows caused by hepatic parenchymal cell and/or intrahepatic bile duct diseases. It commonly occurs as cholestatic liver diseases, intrahepatic cholestasis of pregnancy, and genetic/metabolic-related cholestatic diseases. In recent years, new information and progress in diagnosis and treatment of intrahepatic cholestatic diseases have been achieved. In order to provide updated clinical reference and guidance for clinicians, we organized experts to compile the Expert Consensus on the Diagnosis and Treatment of Intrahepatic Cholestasis (2021), on the basis of the 2015 edition.

Pruritus in cholestasis / Prurido na colestase

Pruritus represents one of the main clinical complaints in medical practice, and leads to significant impairment of life quality and some discomfort. Although the knowledge of its main primary and secondary etiologies is well-established in Internal Medicine, especially in Hepatology, its pathophysiological basis and specific therapeutic-directed approaches are still very complex and need a proper systematization for comprehension. This review aims to present the main current themes regarding the main clinical, pathophysiological, therapeutical and management aspects of cholestasis-associated pruritus. METHODS: The authors performed a wide review of practical clinical guidelines, review articles and original articles from manuscripts published and indexed in PubMed. CONCLUSIONS: Pruritus in cholestasis represents a complex symptom in clinical practice and can be secondary to different pathophysiological mechanisms; its early recognition allows a proper therapeutic approach in most cases.

O prurido representa uma das principais queixas clínicas na prática médica e origina importante comprometimento da qualidade de vida, além de desconforto. Apesar de suas principais etiologias primárias e secundárias serem de conhecimento bem estabelecido na Clínica Médica, em especial na Hepatologia, suas bases fisiopatológicas e os princípios da terapêutica específica direcionada são bastante complexos e necessitam uma sistematização adequada para sua compreensão apropriada. Esta revisão objetiva abordar os principais temas atuais referentes às bases clínicas, fisiopatológicas, terapêuticas e de manejo do prurido relacionados à colestase. Os autores realizaram ampla revisão em diretrizes clínicas práticas, artigos de revisão e publicações originais de artigos publicados e indexados na base PubMed. O prurido na colestase representa um sintoma complexo na prática clínica e pode decorrer de diferentes mecanismos fisiopatológicos secundários. Seu reconhecimento precoce possibilita a abordagem terapêutica apropriada na maioria dos casos.

Nutritional evaluation of children with chronic cholestatic disease / Avaliação nutricional de crianças com colestase crônica

Abstract Objective: To evaluate the nutritional status of children with persistent cholestasis and to compare the anthropometric indices between children with and without liver cirrhosis and children with and without jaundice. Methods: Children with persistent cholestasis, i.e. increased direct bilirrubin or changes in the canalicular enzyme gamma-glutamyl transferase (GGT), were included. The anthropometric measures were weight (W), height or length (H), arm circumference (AC), triceps skinfold thickness (TST), arm muscle circumference (AMC), and body mass index (BMI). Results: Ninety-one children with cholestasis, with current median age of 12 months, were evaluated. W/age (A) and H/A indices below −2 Z-scores were observed in 33% and 30.8% of patients, respectively. Concerning the W/H index and BMI, only 12% and 16% of patients, respectively, were below −2 Z-scores. Regarding AC, 43.8% of 89 evaluated patients had some depletion. Observing the TST, 64% of patients had depletion, and 71.1% of the 45 evaluated patients had some degree of depletion regarding the ACM index. Conclusion: Evaluation using weight in patients with chronic liver diseases may overestimate the nutritional status due to visceromegaly, subclinical edema, or ascites. Indices that correlate weight and height, such as W/H and BMI, may also not show depletion because of the chronic condition in which there are depletion of both weight and height. TST, AC, and ACM are parameters that better estimate nutritional status and should be part of the management of patients with liver diseases and cholestasis.

Resumo Objetivo: Avaliar a situação nutricional de crianças com colestase persistente e comparar os índices antropométricos entre crianças com e sem cirrose hepática e crianças com e sem icterícia. Métodos: Foram incluídas crianças com colestase persistente, ou seja, aumento da bilirrubina direta ou alterações na enzima canalicular, gamaglutamiltransferase (GGT). As medidas antropométricas foram peso, estatura ou altura, circunferência do braço (CB), espessura da prega cutânea do tríceps (TST), circunferência muscular do braço (CMB) e índice de massa corporal (IMC). Resultados: Foram avaliadas 91 crianças com colestase, com idade média de 12 meses; 33% e 30,8% dos pacientes apresentaram índices P/I e A/I com escore Z abaixo de –2, respectivamente. Com relação ao índice P/A e IMC, somente 12% e 16% dos pacientes, respectivamente, apresentaram escore Z abaixo de –2. Com relação à CB, 43,8% de 89 pacientes avaliados apresentaram alguma depleção. Observando a TST, 64% dos pacientes que apresentaram depleção, 71,1% dos 45 pacientes avaliados apresentaram algum grau de depleção com relação ao índice de CMB. Conclusão: A avaliação do peso em pacientes com doenças hepáticas crônicas poderá superestimar a situação nutricional devido a visceromegalia, edema subclínico ou ascite. Os índices que correlacionam peso e altura, como P/A e IMC, também podem não mostrar depleção devido à doença crônica em que há depleção tanto do peso quanto da altura. A TST, BC e CMB são parâmetros que estimam melhor a situação nutricional e devem fazer parte de gestão de pacientes com doenças hepáticas e colestase.

Grape seed protects cholestatic rats liver from ischemia/reperfusion injury

ABSTRACT PURPOSE: To determine the effect of grape-seed extract against ischemia/reperfusion injury in cholestatic liver. METHODS: Eighteen Wistar albino rats were divided into three groups. In control and study groups, cholestasis was provided by bile duct ligation. Seven days later, the rats were subjected to 30 min hepatic ischemia, followed by 60 min of reperfusion. Oral administration of 50 mg/kg/day grape-seed extract was started 15 days before bile duct ligation and continued to the second operation in the study group. Serum, plasma and liver samples were taken. Laboratory analysis, tissue gluthation, malondialdehyde, myeloperoxidase levels and histopathological examination were performed. RESULTS: Significant decrease in liver gluthation level and significant increase in malondialdehyde level and myeloperoxidase activity were observed after ischemia/reperfusion in cholestatic rats. Serum and plasma levels for laboratory analysis were also significantly higher in cholestatic I/R group. Hepatic necrosis and fibrosis were detected in histopathological examination. Oral grape-seed extract administiration reversed all these parameters and histopathological findings except serum bilirubin levels. CONCLUSION: Oral grape-seed extract treatment can improve liver functions and attenuate the inflammation and oxidative stress in cholestatic ischemia/reperfusion injury.

Nuevas terapias para la colestasis / New therapies in cholestasis

The introduction of ursodeoxycholic acid (UDCA) in the treatment of patients with cholestasis enabled remarkable progress and improvements in hepatic inflammatory activity, progression to cirrhosis and quality of life. However, the benefits of UDCA are particularly evident in patients with primary biliary cirrhosis and also 30 percent of patients have sub optimal response. For this reason, in order to improve the number of people with complete responses to therapy, new pharmacological alternatives have been investigated to add to UDCA treatment. This review aims to show potential new therapies against cholestasis that have been investigated by systematizing them depending on the receptor or target on which they act. Finally, a special reference will be made in relation to the treatment of pruritus associated with cholestasis.

La introducción del ácido ursodeoxicólico (AUDC) en el tratamiento de los pacientes con colestasia permitió notables avances con mejoras en la actividad inflamatoria hepática, progresión hacia la cirrosis y calidad de vida. Sin embargo, los beneficios de AUDC se aprecian especialmente en pacientes con cirrosis biliar primaria y además, 30 por ciento de los pacientes tiene una respuesta sub óptima. Por esta razón, con la finalidad de mejorar el número de personas con respuestas completas a la terapia, se han investigado nuevas alternativas farmacológicas para adicionar al tratamiento con AUDC. La presente revisión pretende mostrar las nuevas posibles terapias contra la colestasia estudiadas sistematizándolas según el tipo de receptor o diana sobre el que actúan. Finalmente se hará referencia especial en relación al tratamiento del prurito asociado a la colestasia.

Colédoco-duodenostomía guiada por ecoendoscopia en cáncer de páncreas avanzado con obstrucción duodenal / Endoscopic ultrasound-guided choledocho-duodenostomy in advanced pancreatic cancer with duodenal obstruction

La colangiopancreatografía retrógrada endoscópica (CPRE) se considera el tratamiento de primera línea para el drenaje biliar en pacientes con cáncer de páncreas. En los casos de fracaso por CPRE, generalmente se realiza un drenaje biliar transparietohepático o una derivación biliar quirúrgica. En la última década, las indicaciones y la utilidad de la ecoendoscopia en pacientes con cáncer de páncreas han ido creciendo, y se han informado numerosos casos de drenajes biliares guiados por ecoendoscopia como una alternativa al drenaje biliar percutáneo o quirúrgico en fracasos en la CPRE. Nuestro objetivo es comunicar un caso con cáncer de páncreas localmente avanzado que se presentó con ictericia indolora y síndrome coledociano con obstrucción biliar y duodenal, en el que se realizó una colédoco-duodenostomía guiada por ecoendoscopia mediante la colocación de una prótesis metálica autoexpandible.

Endoscopic retrograde cholangiopancreatography (ERCP) is considered the first-approach for biliary drainage. In cases of ERCP failure, patients are usually referred for percutaneous transhepatic biliary drainage or surgical biliary bypass. In the last decade, the indications of endoscopic ultrasound (EUS) in the management of patients with pancreatic cancer have increased, and numerous cases of EUS-guided biliary drainage have been reported in patients with failures during the ERCP. Our goal is to report a patient with locally advanced pancreatic cancer who presented with painless jaundice and cholestasis with biliary and duodenal obstruction. A EUS-guided choledochoduodenostomy was performed by placement of a self-expanding metal stent.

Dynamic expression of desmin, α-SMA and TGF-β1 during hepatic fibrogenesis induced by selective bile duct ligation in young rats

We previously described a selective bile duct ligation model to elucidate the process of hepatic fibrogenesis in children with biliary atresia or intrahepatic biliary stenosis. Using this model, we identified changes in the expression of alpha smooth muscle actin (α-SMA) both in the obstructed parenchyma and in the hepatic parenchyma adjacent to the obstruction. However, the expression profiles of desmin and TGF-β1, molecules known to be involved in hepatic fibrogenesis, were unchanged when analyzed by semiquantitative polymerase chain reaction (RT-PCR). Thus, the molecular mechanisms involved in the modulation of liver fibrosis in this experimental model are not fully understood. This study aimed to evaluate the molecular changes in an experimental model of selective bile duct ligation and to compare the gene expression changes observed in RT-PCR and in real-time quantitative PCR (qRT‐PCR). Twenty-eight Wistar rats of both sexes and weaning age (21-23 days old) were used. The rats were separated into groups that were assessed 7 or 60 days after selective biliary duct ligation. The expression of desmin, α-SMA and TGF-β1 was examined in tissue from hepatic parenchyma with biliary obstruction (BO) and in hepatic parenchyma without biliary obstruction (WBO), using RT-PCR and qRT‐PCR. The results obtained in this study using these two methods were significantly different. The BO parenchyma had a more severe fibrogenic reaction, with increased α-SMA and TGF-β1 expression after 7 days. The WBO parenchyma presented a later, fibrotic response, with increased desmin expression 7 days after surgery and increased α-SMA 60 days after surgery. The qRT‐PCR technique was more sensitive to expression changes than the semiquantitative method.

Clinical Features and Risk Factors for Severe Complications among Patients with Acute Hepatitis A Virus Infection in The Jeonbuk Province of Korea / 대한소화기학회지

BACKGROUND/AIMS: The frequency of symptomatic acute HAV infections in adulthood are increasing in Korea. This study analyzes the clinical severity in patients with acute HAV infection and investigates risk factors associated with three severe complications: prolonged cholestasis, acute kidney injury, and acute liver failure. METHODS: We performed a retrospective analysis of 726 patients diagnosed from January 2006 to December 2010 at three tertiary hospitals in Jeonbuk Province, Republic of Korea with acute HAV infection. RESULTS: In the group of 726 patients, the mean age was 30.3 years, 426 (58.6%) were male, and 34 (4.7%) were HBsAg positive. Severe complications from acute HAV infection occurred as follows: prolonged cholestasis in 33 (4.6%), acute kidney injury in 17 (2.3%), and acute liver failure in 16 (2.2%). Through multivariate analysis, age > or =40 years (OR 2.63, p=0.024) and peak PT (INR) > or =1.5 (OR 5.81, p=0.035) were found to be significant risk factors for prolonged cholestasis. Age > or =40 years (OR 5.24, p=0.002) and female gender (OR 3.11, p=0.036) were significant risk factors for acute kidney injury. Age > or =40 years (OR 6.91, p=0.002), HBsAg positivity (OR 5.02, p=0.049), and peak total bilirubin (OR 1.11, p=0.001) were significant risk factors for acute liver failure. CONCLUSIONS: Age > or =40 years, female gender, HBsAg positivity, peak PT (INR) > or =1.5, and peak total bilirubin were significant risk factors for severe complications in acute HAV infections.

Síndrome de Alagille experiencia clínica de catorce casos en Medellín, Colombia / Alagille syndrome, clinical experience of fourteen cases in Medellin, Colombia

Introducción: El Síndrome de Alagille corresponde a una alteración autosómica dominante con expresión variable. Se caracteriza por colestasis crónica con escasez de los conductos biliares interlobulares asociada a alteraciones cardiovasculares, oftálmicas, sistema esquelético, riñones y facies característica. Su distribución es mundial con frecuencia de 1 por cada 100000 nacidos vivos. Objetivo: Describir las características clínicas, la evolución y la sobrevida de catorce pacientes, con diagnóstico de Síndrome de Alagille atendidos en un período de 16 años en Medellín, Colombia. Materiales y métodos: Es un trabajo observacional descriptivo de reporte de casos de los hallazgos morfológicos y la evolución de los pacientes con diagnóstico de Síndrome de Alagille. Resultados: Grupo compuesto por ocho niños y seis niñas, con edades entre los dos meses y los diez años al momento de diagnóstico. El síndrome completo se presentó en 28%. Los hallazgos más frecuentes, estenosis valvular de la arteria pulmonar y la alteración vertebral se presentaron en el 79%. Tres pacientes 21%, fallecieron, uno de ellos después de recibir trasplante hepático. De los once sobrevivientes dos niñas fueron sometidas a trasplante y se encuentran en buenas condiciones. Los nueve restantes padecen hepatopatía colestásica crónica y reciben tratamiento médico. Conclusión: El Síndrome de Alagille se debe tener en cuenta en el diagnóstico de colestasis crónica infantil. Para establecer la distribución y frecuencia de esta enfermedad en nuestro país es necesario desarrollar investigaciones que idealmente incluyan el estudio de la mutación genética en los pacientes y su familia cercana.

Introduction: The Alagille Syndrome is an autosomic dominant disorder with variable expression. Chronic cholestasis, characteristic facial appearance and abnormalities heart, skeleton, eye, kydnes with hypoplasia of the biliary ducts. Initial description in France, with mundial distribution her frecuence is 1/100000. Objective: To describe the clinical characteristic and evolutions of fourteen patients with diagnosis Alagille Syndrome in Medellín Colombia. Materials and methods: Descriptive retrospective study with variables obtained from clinical records of patients with diagnosis Alagille Syndrome. Results: Eight boys and six girls. The age at diagnosis varied two months at nine years. Complete syndrome was present in 28%. The most frecuent alterations were valvular stenosis pulmonary artery and failure of anterior vertebral arch fusion (butterfly vertebrae) 79%. The clinical evolution was variable, death occurred in three patients 21%, one girl post liver transplantation. Nine children had chronic hepatopathy controlled with medical treatment and two girls had liver transplantation with satisfactory evolution. Conclusions: In Colombia, the poblational incidence is not defined it is necessary to know the distribution of syndrome at future study.

Drug rash with eosinophilia and systemic symptoms syndrome following cholestatic hepatitis A: a case report / 대한간학회지

Hepatitis A virus (HAV) infections occur predominantly in children, and are usually self-limiting. However, 75-95% of the infections in adults are symptomatic (mostly with jaundice), with the illness symptoms usually persisting for a few weeks. Atypical manifestations include relapsing hepatitis, prolonged cholestasis, and complications involving renal injury. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, drug-induced hypersensitivity reaction characterized by skin rash, fever, lymph-node enlargement, and internal organ involvement. We describe a 22-year-old male who presented with acute kidney injury and was diagnosed with prolonged cholestatic hepatitis A. The patient also developed DRESS syndrome due to antibiotic and/or antiviral treatment. To our knowledge, this is the first report of histopathologically confirmed DRESS syndrome due to antibiotic and/or antiviral treatment following HAV infection with cholestatic features and renal injury.

Estenosis biliares benignas: experiencia 77 casos / Benign biliary strictures: experience 77 cases

Se presenta la experiencia de los autores con 77 casos de estenosis biliares benignas tratadas en Unidad de Cirugía Hepática, Biliar y trasplante de hígado del Hospital Universitario de Maracaibo. Desde agosto de 1989 hasta diciembre de 2009, fueron registrados 77 casos de estenosis biliares benignas. Se tipificaron según la clasificación de Bismuth. 83,12% (64) de los pacientes habían sido colecistectomizados (estenosis post-iatrogenia durante este procedimiento): 41 (53,25%) abiertas y 23 (29,87%) laparoscópicas. 89,61 (69) de los pacientes consultaron por ictericia, 62,34% fiebre y 58,44% dolor abdominal. 9% (7) presentó estenosis Bismuth I, 22% (17) tipo II, 44,16% (34) tipo III y 24,68% (19) tipo IV. A todos se les realizó exploración biliar quirúrgica y anastomosis mucosa-mucosa con Y-Roux, tipo Hepp-Couinaud en 70 (87,5%) de los pacientes. La mortalidad fue 2,6% (2) paciente en el transoperatorio. Se presentaron en el peri-operatorio 19 (24,39%) complicaciones en 17 (22%) pacientes: 12 (15,6%) mayores y 7 (8,79%) menores. En un seguimiento promedio de 49 meses, 7-79% (6) pacientes presentaron re-estenosis de la derivación bilioentérica. El mayor porcentaje de estenosis biliares benignas son posteriores a procedimientos quirúrgicos, principalmente colecistectomia. La anastomosis bilioentérica tipo Hepp-Couinaud se realizó en el mayor número de pacientes con excelentes resultados.

Present experience of the authors with 77 cases of bening biliary strictures. From August of 1989 to December of 2009, 77 patients were recorded. Classification of Bismuth was used to classificate the strictures 64 (83,12%) patients were cholecistectomizated (stricture by iatrogenia during this procedure): 41 (53,25%) open and 23 (29,87%) laparoscopic. 89,61% (69) consulted by jaundice, 62,34 by fever and 58,44% by abdominal pain. 9%(7) had stricture Bismuth 1,22% (17) type II, 44,16% (34) type III and 24,68% (19) type IV. All patients were summated to surgical biliary exploration and mucous-mucous biliary anastomosis with Y-Roux. Hepp-Couinaud type in 70 (87,7%) of the patients. Perioperative mortality was 2,6% (2). Perioperative complications were 19 (24,39%) in 17 (22%) patients: 12 (15,6%) mayor and 7(8,79%) minors. In medial following of 49 months, 7,79% (6) presented re-stricture of bilio-enteric anastonosis. The majority of the strictures were due to surgical procedures. Hepp-Couinaud anastomosis was performed in almost all the patients with excellent outcome.

Colestasis: enfoque actual / Cholestasis: current approach

La colestasis, tiene incidencia de 1:60-375 ictéricos a las 2 semanas de edad, es potencialmente grave, presentan riesgos inmediatos como coagulopatías por hemorragia severa ante el déficit de la absorción de la vitamina K, y con su diagnóstico precoz, se identifican patologías que tienen tratamiento, incluso, trasplante hepático. Como consecuencia de la colestasis, hay retención de sales biliares, daño celular hepático, y descenso de la bilis a nivel intestinal, que ocasionan mala digestión de grasas y proteínas, con defectos en las vitaminas liposolubles. Existen hepatopatías primariassecundarias a una serie de entidades genéticas y metabólicas, y colestasis secundarias a otros problemas, que en el adulto generan enfermedad hepática. Es necesario establecer protocolos deidentificación del niño con ictericia.

Cholestasis has 1:60-375 incidence of jaundice at 2 weeks of age, are potentially serious, immediateand present risk of severe bleeding coagulopathy to the shortfall in the absorption of vitamin K, andearly diagnosis, identify diseases that are treatable, even liver transplantation.As a result of cholestasis, there is retention of bile salts, liver cell damage and decrease of bile in the intestine, causing poor digestion of fats and protein, with defects in soluble vitamins. There are primaryliver disease secondary to a variety of metabolic and genetic entities, and cholestasis secondary toother problems, generated in the adult liver disease. It is necessary to establish protocols for the identification of children with jaundice.

Antagonista de opioides para o tratamento do prurido associado à colestase. Relato de caso / Opiate antagonist therapy for the cholestasis pruritus. Case report

JUSTIFICATIVA E OBJETIVOS: Pacientes com lep­tospirose podem desenvolver colestase, levando à queixa de prurido. Existem vários tratamentos propostos para o prurido, porém nenhum deles é satisfatoriamente efetivo. O objetivo deste artigo foi relatar o emprego de um antagonista opioide para o tratamento de prurido associado à 3 colestase em paciente com leptospirose.RELATO DO CASO: Paciente do sexo masculino, 51 anos, apresentou quadro de leptospirose, referindo dentre 11 as principais queixas prurido intenso. A queixa manteve-se até o quarto dia de internação, quando se optou pelaprescrição de um antagonista opioide, levando à remissão completa do quadro. CONCLUSÃO: O sucesso da terapia no caso apresentado soma-se a outros relatos da literatura que demonstram evidências de que os antagonistas opioides são bem tolerados e rêduzem significativamente o prurido associado à colestase.

Suplementação com ácido ascórbico tem efeito citoprotetor na cirrose biliar secundária: estudo experimental em ratos jovens / Ascorbic acid supplementation has a cytoprotective effect on secondary biliary cirrhosis: experimental study in young rats

OBJETIVO: Testar se a suplementação com ácido ascórbico tem algum afeito citoprotetor em um modelo de cirrose biliar secundária em ratos jovens. MÉTODOS: Foram estudados 40 ratos Wistar desmamados no 21º dia pós-natal. Cada grupo de 10 foi submetido a um dos seguintes quatro tratamentos, até o 49º dia pós-natal, quando foram submetidos a eutanásia: 1) LC - ligadura dupla e ressecção do ducto biliar comum e administração diária de ácido ascórbico [100 mg/g de peso corporal (pc)]; 2) LA - ligadura dupla e ressecção do ducto biliar comum e administração diária de veículo aquoso (1 mL/g pc); 3) SC - operação simulada e administração diária de ácido ascórbico (100 mg/g pc); 4) SA - ligadura dupla e ressecção do ducto biliar comum e administração diária de veículo aquoso (1 mL/g pc). Os ratos eram pesados diariamente. No 27º dia pós-operatório, eles receberam injeção intraperitoneal de 1,5 mg/g pc de pentobarbital sódico, e o tempo de sono induzido pelo pentobarbital foi medido. Coletou-se sangue para determinação de atividade sérica de alanina aminotransferase e de aspartato aminotransferase, níveis de albumina e globulina séricas, e o fígado foi analisado quanto à conteúdo de água e gordura. Os dados foram submetidos à ANOVA two-way, e comparações pareadas entre grupos foram testadas com o método de SNK. O nível de significância foi estabelecido em 0,05. RESULTADOS: A suplementação com ácido ascórbico atenuou os efeitos da colestase: reduziu o tempo de anestesia pelo pentobarbital, globulina sérica e o conteúdo de gordura no fígado. CONCLUSÕES: Nossos resultados corroboram a hipótese de que a suplementação com ácido ascórbico tem um efeito citoprotetor na cirrose biliar secundária.

OBJECTIVE: To test whether ascorbic acid supplementation has any cytoprotective effect on a model of secondary biliary cirrhosis in young rats. METHODS: We studied 40 Wistar rats weaned at the 21st postnatal day. Each group of 10 was subjected to one of the following four treatments, until 49th postnatal day, when they suffered euthanasia: 1) LC-double ligature and resection of the common bile duct and daily administration of ascorbic acid [100 mg/g of body weight (bw)]; 2) LA-double ligature and resection of the common bile duct and daily administration of aqueous vehicle (1 mL/g bw); 3) SC-sham operation and daily administration of ascorbic acid (100 mg/g bw); 4) SA-double ligature and resection of the common bile duct and daily administration of aqueous vehicle (1 mL/g bw). The rats were weighed daily. On the 27th day after the operation they received an intra-peritoneal injection of 1.5 mg/g bw of sodium pentobarbital, and the pentobarbital sleeping time was measured. Blood was collected for serum alanine aminotransferase and aspartate aminotransferase activity measurements, serum albumin and globulin concentrations, and the liver was assessed for liver water and fat content. Data were submitted to two-way ANOVA and paired comparisons between groups were tested using the SNK method. Significance level was set at 0.05. RESULTS: Ascorbic acid supplementation attenuated the effects of cholestasis: decreased the pentobarbital sleeping time, serum globulin, and the liver fat content. CONCLUSIONS: Our results corroborate the hypothesis that ascorbic acid supplementation has a cytoprotective effect in secondary biliary cirrhosis.

Effects of low fat and babassu fat diets on nutritional status in obstructive cholestasis in young rats

PURPOSE: To test the effects of a low fat diet compared with a babassu fat diet on nutritional status in obstructive cholestasis in young rats. METHODS: We submitted 40 rats in 4 groups of 10 animals each from P21 (21st postnatal day) to P49 to two of the following treatments: bile duct ligation or sham operation and low fat diet (corn oil supplying 4.5 percent of the total amount of energy) or babassu fat diet (this fat supplying 32.7 percent and corn oil supplying 1.7 percent of the total amount of energy). Weight gain from P25 to P49 every 4 days was measured. The Verhulst's growth function was fitted to these values of weight gain. Growth velocity and acceleration at each moment were estimated using the same equation. Total food and energy intake from P21 to P49, energy utilization rate (EUR) from P25 to P49 and fat absorption rate (FAR) and nitrogen balance (NB) from P42 to P49 were measured. Two Way ANOVA and the S.N.K. test for multiple paired comparisons were employed to study the effects of cholestasis and those of the diets and their interaction (p<0.05) on those variables. RESULTS: In cholestatic animals, a higher growth velocity at P45, a higher growth acceleration at P41 and P45, a greater EUR, a greater FAR and a greater NB, were found with the low fat diet as compared with the babassu fat diet. CONCLUSION: A low fat diet lessens the growth restriction brought about by cholestasis and allows for an improved dietary energy utilization and a better protein balance than the babassu fat diet.

OBJETIVO: Testar os efeitos de uma dieta com baixo teor de gordura comparada a uma dieta com gordura de babaçu sobre o estado nutricional em ratos jovens com colestase obstrutiva. MÉTODOS: Submetemos 40 ratos divididos em quatro grupos de 10 animais a partir do P21 (21º dia pós-natal) até o P49 a dois dos seguintes tratamentos: ligadura e ressecção do ducto biliar comum ou operação simulada e dieta com baixo teor de gordura (óleo de milho fornecendo 4,5 por cento da quantidade total de calorias) ou dieta com gordura de babaçu (essa gordura fornecendo 32,7 por cento e óleo de milho fornecendo 1,7 por cento da quantidade total de calorias). Foi mensurado o ganho de peso a cada 4 dias do P25 ao P49. A função de crescimento de Verhulst foi ajustada aos valores de ganho de peso. A velocidade e a aceleração de crescimento nos mesmos momentos foram estimadas usando a mesma equação. Foram mensurados: quantidade de ração ingerida e ingestão energética total do P21 ao P49, utilização de energia do P25 ao P49, gordura absorvida e balanço de nitrogênio (BN) do P42 ao P49. A ANOVA com dois fatores e o método de S.N.K para comparações pareadas foram utilizados para estudar os efeitos, sobre as variáveis, da colestase e das dietas e sua interação (p<0,05). RESULTADOS: Em ratos com colestase e dieta com baixo teor de gordura, houve maior velocidade de crescimento no P45, maior aceleração de crescimento no P41 e P45, maior utilização de energia, maior percentual de gordura absorvida e maior BN do que em ratos com colestase e dieta com gordura de babaçu. CONCLUSÃO: A dieta com baixo teor de gordura atenua a restrição de crescimento provocada pela colestase e proporciona melhor aproveitamento da dieta e maior incorporação da proteína ingerida do que a dieta com gordura de babaçu.

effects of N-acetylcysteine and vitamin C on liver and pulmonary tissue damage in rats following bile duct ligation

To evaluate the effects of N-acetylcysteine NAC and vitamin C on pulmonary histological alterations in bile duct-ligated [BDL] rats. The current study was conducted in the Department of Pediatric Surgery, Medical School of Abant Izzet Baysal University, Bolu, Turkey between May 2007 and July 2007. Thirty-five males Sprague-Dawley rats, weighing 210-240 grams, were used. Group 1 rats [n=7] underwent only laparotomy. Group 2 rats [n=7] were subjected to BDL. Group 3 rats [n=7] were subjected to BDL and given vitamin C. Group 4 rats [n=7] were subjected to BDL and given NAC. Group 5 rats [n=7] were subjected to BDL and received NAC plus vitamin C. At the end of the 3 week period, biochemical and histological evaluations were processed. Total bilirubin values were decreased in group 5 compared to group 2, 3, and 4. Group 2 showed massive interstitial infiltration with inflammatory cells. Interstitial edema, focal cuboidal metaplasias of alveolar lining cells, and severely damaged pulmonary architecture were noted. Treatment of rats with NAC and vitamin C produced a significant reduction in the histopathological score compared to groups 2, 3, and 4. The combination of NAC and vitamin C reduced lung histological alterations in BDL rats with afforded by each drug individually