Protective effect of water extracts of Orychophragmus violaceus seeds on TAA-induced acute liver injury in mice / 中国中药杂志

This study aimed to investigate the protective effect of water extracts of Orychophragmus violaceus seeds on liver injury induced by thioacetamide(TAA) in mice. ICR male mice were randomly divided into seven groups: normal group, model group, bicyclol positive control group(200 mg·kg~(-1)), Kuihua Hugan Tablets group(350 mg·kg~(-1)), O. violaceus seeds low-dose water extract group(125 mg·kg~(-1)), middle-dose water extract group(250 mg·kg~(-1)), and high-dose water extract group(500 mg·kg~(-1)). Intragastric administration was given in all groups at 0.02 mL·g~(-1) body weight, 1 time a day for continuous 4 days. One h after the administration on the 4 th day, the liver injury model was induced by intraperitoneal injection of TAA(100 mg·kg~(-1)). The mice were put to death 24 hours later. Blood and tissues were taken and organ indexes were calculated. The activities of ALT, AST and TBiL in serum were detected. The content of MDA, GSH and the activity of SOD, GSH-Px in liver homogenate were examined by colorimetry method. HE staining was used to observe the pathological changes of liver tissues in mice. The protein expression levels of NF-κB p65, Keap-1, Nrf2, p-p38, p-JNK, p-ERK, Bax, Bcl-2, caspase-3, cleaved caspase-3 and caspase-8 were detected by Western blot. The results showed that as compared with the model group, various O. violaceus seeds groups could significantly improve the pathological conditions of liver and reduce ALT, AST, TBiL activities in serum of mice with liver injury. In the high-dose group, the activities of SOD, GSH-Px and the content of GSH were significantly increased, while MDA content was sharply declined. Meanwhile, O. violaceus seeds extract down-regulated the expressions of Bax, Keap-1, p-p38, p-JNK, p-ERK, NF-κB p65, cleaved caspase-3 and up-regulated the expressions of Nrf2, Bcl-2, caspase-3 and caspase-8. In conclusion, O. violaceus seeds extract exhibited potent protective effect on liver injury induced by TAA in mice, and its mechanism may be related to down-regulating levels of Keap-1, up-regulating the expressions of Nrf2, inhibiting the expressions of p-p38, p-ERK and NF-κB p65 signaling pathway, and inhibiting hepatocyte apoptosis by down-regulating the expressions of p-JNK and Bax and up-regulating the expressions of Bcl-2.

Thoraco-Acromial Artery : A Cadaveric Study Of Its Pedicle And Branches

Background of study- A detailed knowledge of variations in the origin and branching pattern of Thoraco-acromial artery(TAA) is important during various reconstructive and microvascular surgeries. Materials and methods- Hundred formalin xed specimens were studied at Government Medical College, Kozhikode, Kerala, India over a period of four years. Results- Normal quadrifurcation pattern was observed in majority of specimens (84%). The division of TAA into two trunks was seen in 9% followed by ramication into multiple branches in 4% specimens. Some specimens showed trifurcation (3%). Conclusion- In this scenario of increasing reconstructive surgeries, a thorough knowledge on the anatomical variations of TAA will be helpful to surgeons as this artery provides vascular supply to Pectoralis Major Myo-Cutaneous ap.

Terapia assistida por animais e transtornos do neurodesenvolvimento / Animal assisted therapy and neurodevelopmental disorders / Terapia asistida por animales y transtornos del neurodesarollo

Este artigo visa levantar, por meio de construções teórico-científicas, os benefícios que a Terapia Assistida por Animais (TAA) pode gerar quando utilizada para tratamento com crianças que apresentam algum comprometimento neurodesenvolvimental. O contato humano-animal é conhecido desde a antiguidade, porém, apenas na atualidade estudos em torno deste viés estão crescendo. Portanto, foi realizada uma revisão crítica da literatura, analisando os dados coletados a partir de análise de conteúdo. Os resultados apontam o potencial benéfico deste tipo de intervenção com crianças com dificuldades sociais, cognitivas e físicas. Os animais mais utilizados são cachorros e cavalos para tratamento de crianças com Transtorno do Espectro Autista, Síndrome de Down e Deficiência Intelectual. Dessa forma, há uma possibilidade de que os profissionais da Psicologia, e de outras áreas da saúde, utilizem ou encaminhem para a Terapia Assistida por Animais (TAA) seus pacientes. Ainda assim, conclui-se que há a necessidade de mais estudos empíricos. (AU)

This article aims to evaluate, through theoretical and scientific papers, the benefits that Animal Assisted Therapy (AAT) can provide to children who have some neurodevelopmental impairment. The benefits of human-animal contact has been known since antiquity, but studies around this area are starting to grow only currently. Therefore, we performed a critical review of the literature by analyzing the data collected using content analysis. The results showed the potential benefit of this type of intervention to children with social, cognitive and physical disabilities. The most commonly used animals were dogs and horses for treatment of children with Autism Spectrum Disorder, Down Syndrome and Intellectual Disabilities. Thus, there are possibility for psychologists and other professionals of health areas use or referee this kind of intervention to their patients. Still, we can conclude that there is a lack to more empirical studies using AAT. (AU)

El presente artículo tiene por objeto evaluar, por medio de los aportes teóricos y científicos, los beneficios que la Terapia Asistida por Animales- (TAA) puede generar cuando se la utiliza para el tratamiento de niños con algún tipo de compromiso en el desarrollo neurológico y mental. El contacto humano-animal es conocido desde la antigüedad, sin embargo, los estudios en torno a esta tendencia están empezando a crecer sólo en este momento. Por lo tanto, se realizó una revisión crítica de la literatura mediante el análisis de los datos obtenidos por medio del análisis de contenido. Los resultados muestran el beneficio potencial de este tipo de intervención con niños con dificultades sociales, cognitivas y físicas. Los animales más utilizados son el perro y el caballo para el tratamiento de los niños con trastorno del espectro autista, síndrome de Down y Discapacidad Intelectual. De este modo, existe la posibilidad de los profesionales de psicología, y otras áreas del salud, utilizar o indicar este medio de intervención para ayudar en el tratamiento de los pacientes. Aun así, se puede concluir que existe una necesidad de más estudios empíricos. (AU)

Management of concurrent thoracic and abdominal aortic aneurysms

Concurrent thoracic and abdominal aortic aneurysm is uncommon. It remains a formidable surgical challenge to vascular surgeons, as decision to treat in staged or simultaneous setting still debatable. We present, here, a case of a 62-year-old-man with asymptomatic concurrent thoracic and abdominal aortic aneurysms, which was successfully treated with two-stage hybrid endovascular repair. The aim of this case report is to discuss the treatment options available, possible associated complications and measures to prevent them.

Assessment of haemolytic, cytotoxic and free radical scavenging activities of an underutilized fruit, Baccaurea ramiflora Lour. (Roxb.) Muell. Arg.

Baccaurea ramiflora Lour. (Roxb.) Muell. Arg. is an underutilized juicy fruit bearing plant found in sub-Himalayan area, South China, Indo-Burma region, etc. The fruit is considered to be nutritive, and in this study, we evaluated its antioxidant, haemolytic and cytotoxic properties. The juice was examined for the quenching activity of hydroxyl radical, nitric oxide, singlet oxygen, peroxynitrite, total antioxidant activity (TAA), erythrocyte membrane stabilizing activity (EMSA) along with quantification of phenolic and flavonoid contents and also tested for its potential activity as iron chelator, inhibitor of lipid peroxidation and total reducing power. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were also performed to correlate antioxidant capacities with the phenolic and flavonoid content. Haemolytic activity on murine erythrocyte and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxic test was performed on murine splenocytes, thymocytes, hepatocytes and peritoneal exudates macrophage to examine the cytotoxic effect of its juice. The result exhibited its potent free radical scavenging activity. In case of TAA, DPPH (2, 2-diphenyl-1-picrylhydrazyl), EMSA and lipid peroxidation, the fruit juice was found to have significant (P <0.001) antioxidant capacity, which is evident from low IC50 (half maximal inhibitory concentration) value. Results obtained from haemolytic inhibition assay and MTT cytotoxic test confirms that the juice does not contain any cytotoxic effect and the fruit is safe for consumption. Fourier transform infrared (FTIR) spectra analysis exhibited high possibility of presence of flavonoid compounds in the juice.

Expression of IL-1β, IL-6 and TNF-α in rats with thioacetamide-induced acute liver failure and encephalopathy: correlation with brain edema.

Background: Secondary brain edema is a serious complication of hepatic encephalopathy (HE). Recently, it has been reported that proinflammatory cytokines are involved in the pathogenesis of brain edema during HE. Objectives: Observe the dynamic expressions of brain and plasma proinflammatory cytokines in encephalopathy rats, and evaluate the relationship between proinflammatory cytokines and brain edema. Methods: Acute HE rats were induced by intraperitoneal injection of thioacetamide (TAA) in 24 hours intervals for two consecutive days. Then, clinical symptom and stages of hepatic encephalopathy, motor activity counts, index of liver function, and brain water content were observed. The dynamic expressions of IL-1?, IL-6, and TNF-? in plasma and brain tissues were measured with enzyme-linked immunosorbent assay. Results: Typical clinical performances of hepatic encephalopathy were occurred in all TAA-administrated rats. The TAA rats showed lower motor activity counts and higher the index of alanine aminotransferase, aspartate aminotransferase, total bilirubin and ammonia than those in control rats. Brain water content was significantly enhanced in TAA rats compared with the control. The expressions of IL-1?, IL-6, and TNF- ? in plasma and brain significantly increased in TAA rats. In addition, the expressions of cerebral proinflammatory cytokines were positively correlated with brain water content but negatively correlated with motor activity counts. Conclusion: Inflammation was involved in the pathogenesis of brain edema during TAA-induced HE.

Influência do consumo do café (com e sem cafeína) ou da cafeína isolada sobre a fibrose e a promoção da hepatocarcinogênese química em ratos Wistar machos / Influences the consumption of coffee (with or without caffeine) or caffeine isolated on fibrosis and promotion of chemical hepatocarcinogenesis in male wistar rats

O café e a cafeína são dois potenciais agentes preventivos contra o desenvolvimento ou avanço dos processos de fibrose/cirrose e carcinogênese hepática em humanos, entretanto suas ações são controversas e muitas vezes inconclusivas. Devido a isto, o objetivo deste trabalho foi verificar a ação do café ou da cafeína isolada no fígado de ratos Wistar tratados com tioacetamida (TAA) ou tetracloreto de carbono (CCl4). Para tanto, os dados experimentais foram distribuídos em dois artigos. No primeiro artigo, foram avaliados os efeitos do café convencional, descafeinado e da cafeína isolada na hepatotoxicidade induzida pela TAA em ratos Wistar. Para tanto, 60 os animais foram divididos em 5 grupos experimentais: G1 (controle negativo), G2 (controle positivo tratado com TAA 200 mg/Kg i.p.), G3 (TAA + café convencional), G4 (TAA + café descafeinado) e G5 (TAA + cafeína a 0,1%). Ao final de 8 semanas de tratamento os ratos foram eutanasiados para coleta do sangue (análises séricas) e do fígado (análises histológicas, histoquímicas e moleculares). De maneira geral os animais tratados com café/cafeína (G3-G5) apresentaram níveis da enzima alanina aminotransferase (ALT), área ocupada por colágenos I e III e expressão da proteína TGF-beta1 menores que o grupo controle positivo (G2). Adicionalmente, os grupos G3 e G5 apresentaram menor número de núcleos PCNA positivos em fase S do que o grupo G2. O grupo G3 também apresentou menor número de focos GST-P positivos que o grupo G2. Ademais, os grupos G4 e G5 apresentaram as maiores atividades de MMP-2 ativa. Em conclusão, tanto o café convencional como o descafeinado como a cafeína a 0,1% apresentaram efeitos benéficos, mostrando que os outros componentes do café, mesmo sem a cafeína, ou que somente a cafeína são capazes de reduzir a hepatotoxicidade no fígado de ratos Wistar tratados com TAA..(...)

Consumption of coffee beverages reduces the incidence of liver disease. However, whether these beneficial effects on human health are due to caffeine or other specific components in the beverage remains controversial. There, the present study aimed to study evaluated the protective effects of coffee beverages or caffeine on liver toxicity induced by repeated administration of the hepatotoxicant thioacetamide (TAA) in male Wistar rats. Animals were randomized into five groups: untreated controls (G1) TAA only (G2, 200 mg/Kg b.w. twice a week for 8 weeks, i.p.), TAA+conventional coffee (G3), TAA+decaffeinated coffee (G4) and TAA+caffeine (G5, 0.1% in the drinking water). At the end of 8 weeks, the animals were euthanized and blood and liver samples were collected. Serum ALT levels were lower in animals that received coffee and caffeine (p < 0.001). In addition, liver oxidized glutathione (p < 0.05), fibrosis/inflammation score (p < 0.001) and TGF-beta expression (p ¡Ü 0.001) was reduced in these groups when compared to TAA-only rats. Moreover, conventional coffee and caffeine reduced PCNA S-phase index (p < 0.001) but only conventional coffee reduced cleaved caspase-3 index (p < 0.001) and active metalloproteinase 2 (p ¡Ü 0.004) in the liver from TAA-treated animals.(...)

Initial Results of Open Stent-Grafting Applied with a Matsui-Kitamura Stent in the Treatment of Thoracic Aortic Aneurysm / 日本心臓血管外科学会雑誌

We reporte the initial results of open stent-grafting (OSG) applied with a Matsui-Kitamura (MK) stent in the treatment of thoracic aortic aneurysm (TAA). From August 2005 to March 2011, OSG for TAA was applied in 35 cases (male/female, 29/6, 58∼86 years old, mean age 71). During deep hypothermic circulatory arrest with antegrade selective cerebral perfusion, the stent graft was delivered through the transected proximal aortic arch, followed by arch replacement with a 4-branched prosthesis. Concomitant procedures included 1 coronary artery bypass graft, 1 mitral valve replacement and 2 pacemaker implantations. Operative mortality within 30 days was 5.7% (respiratory failure in 1 and ischemic enteritis in 1). There was 1 in-hospital death due to brain stem infarction. Perioperative morbidity included 2 (5.7%) stroke, 5 (14.3%) spinal cord injuries (paraplegia in 1, paraparesis in 1 and transient paraparesis in 3) , and 1 (2.9%) temporary hemodialysis. Ten patients (28.6%) were intubated for more than 72 h. There was no complication with the graft-related incident. These initial results suggested the OSG method applied with a MK stent is a useful surgical procedure for the treatment of TAA.

Anti-hepatofibrogenic Effect of Turnip Water Extract on Thioacetamide-induced Liver Fibrosis / 한국실험동물학회지

Liver fibrosis is a chronic liver disease and lots of people in Korea are suffered. There are many efforts to find candidates to suppress liver fibrogenesis and several chemical-induced model or bile duct ligation model have been used to research and develop hepatic fibrogenic suppressor. From the previous study about functional effects of turnip which cultivated in Kangha Island, we got the feasibility which turnip might be able to inhibit heptatic fibrogenesis. TAA is a representative hepatic fibrosis inducer, repeated 7-weeks i.p. injection of it results in hepatic fibrosis. We compared the level of hepatic fibrosis in TAA-turnip group, TAA group, and vehicle control group. Nodules-formed by TAA were observed; they were rarely shown in vehicle control group, observed in most area in TAA group, but only shown in periportal regions in TAA-turnip group. These results were confirmed through Masson's trichrom stain; fibrous structures increased in TAA group (fibrosis score: 4) but significantly decreased in TAA-turnip group (fibrosis score: 2-3). In conclusion, we got the result that turnip water extract has a potency to protect TAA-induced hepatic fibrogenesis but it is necessary further study to find its mechanism.

Active Immunization Study of Colon Cancer Derived 1-8D Peptide in HHD Mice

BACKGROUND: 1-8D gene is a member of human 1-8 interferon inducible gene family and was shown to be overexpressed in fresh colon cancer tissues. Three peptides 1-6, 3-5 and 3-7 derived from human 1-8D gene were shown to have immunogenicity against colon cancer. METHODS: To study tumor immunotherapy of three peptides we established an active immunization model using HHD mice. D(b-/-) x beta2 microglobulin (beta2 m) null mice transgenic for a chimeric HLA-A2.1/D(b-)beta2 m single chain (HHD mice) were challenged with B16/HHD/1-8D tumor cells and were immunized with irradiated peptide-loaded RMA- S/HHD/B7.1 transfectants. In therapy model tumor growth was retarded in HHD mice that were injected with 3-5 peptide-loaded RMA-S/HHD/B7.1. In survival test vaccination with 1-8D-derived peptide protects HHD mice from tumor progression after tumor challenge. RESULTS: These studies show that peptide 3-5 derived from 1-8D gene can be the most effective candidate for the vaccine of immunotherapy against colon cancer and highlight 1-8D gene as putative colon carcinoma associated antigens. CONCLUSION: We demonstrated that RMA-S/HHD/ B7.1 loaded with 1-8D peptides, especially 3-5, immunization generates potent antitumor immunity against tumor cells in HHD mice and designed active immunization as proper immunotherapeutic protocols.

A implantação da estratégia DOTS na cidade do Rio de Janeiro / Implementation of the DOTS strategy in the city of Rio de Janeiro

Introdução: o objetivo deste estudo foi descrever a implementação da estratégia DOTS (Estratégia de Tratamento Diretamente Observado de Curta duração) nos centros de saúde na cidade do Rio de Janeiro, apresentando os resultados obtidos após dois anos de desenvolvimento de projetos-piloto. Métodos: análise dos dados contidos nos "Livros de Registro e Controle do Tratamento", regularmente notificados à Secretaria Municipal de Saúde do Rio de Janeiro, visando avaliar o impacto do tratamento diretamente observado (DOT) nos índices de cura e o efeito da implementação da estratégia DOTS na qualidade do programa de controle da tuberculose (PCT). Resultados: De Janeiro de 1999 a Dezembro de 2001, 3657 casos de TB foram registrados nas áreas onde a estratégia DOTS foi implantada. Destes, 1730 receberam DOT e 1927 receberam tratamento auto-administrado (TAA). Entre os caos novos, 81% dos que receberam DOT e 71% dos que receberam TAA foram tratados com sucesso (OR 1,66, IC 95%: 1,3 -1,8), p<0,01. As taxas de negativação da baciloscopia do escarro após 2 e 3 meses de tratamento foram de 84% e 91% respectivamente para aqueles que receberam DOT e 75% e 83% para o grupo em TAA. Nos centros de saúde onde a estratégia DOTS foi implantada houve, em 3 anos, melhora geral dos índices de cura e de abandono, assim como dos percentuais de baciloscopias realizadas para acompanhamento do tratamento. Conclusão: Pacientes que receberam DOTS tiveram maior chance de cura do que aqueles que receberam TAA. A implantação da estratégia DOTS melhorou a qualidade do PCT.

Introduction: The objective of this study is to describe the implementation of DOTS (Directly Observed Treatment, Short course) strategy in health centers in the city of the Rio de Janeiro presenting the results 2 years after teh development of pilot projects. Methods: analysis of data recorded on the "TB treatment and outcome registration books", regularly reported to the City Health Secretariat, to evaluate the results of the directly observed therapy (DOT) on the treatment success rates and the effect of DOTS implementation on the equality of the TB control program. Results: From January 1999 to December 2001, 3,657 TB cases were registered in the areas where the DOTS strategy was implemented. Of these, 1,730 received directly observed treatment (DOT) and 1,927 received self-administered treatment (SAT). In the DOT group 81% of the new cases were treated successfully, whereas in the SAT 71% of the new cases were treated successfully (OR1,66, 95% CI:1,3 -1,8, p <0,01). The sputum smear conversion rates for the new cases after 2 and 3 months' treatment were respectively 84% and 91% for the group on DOT and 75% and 83% for those on SAT. In the health centers where the DOTS strategy was implemented there was a general improvement on the cure and default rates, and also on the proportion of patients monitored bacteriologically during treatment. Conclusion: patients receiving DOT were much more likely to complete treatment than those receiving SAT. The implementation of the DOTS strategy improved the quality of the TB control program.

Vínculo anciano-mascota: condiciones y consecuencias. ¿Al servicio de la salud o al servicio de la patología? / Link elder-pet: conditions and consequences. In service of health or pathology service?

El punto de partida de esta investigación es explorar las posibilidades de aplicación en nuestro medio, con ancianos, de la llamada internacionalmente ¨Terapia Asistida por Animales¨ (TAA), como un enfoque interdisciplinario que implica la introducción de animales en la rutina de una persona, o grupo de personas, con fines terapéuticos. De acuerdo a este enfoque se considera que, si bien los animales por sí solos no ejercen un efecto terapéutico, pueden proveer estímulos que favorecen la terapia y la red social de apoyo. En Argentina no existen estudios acerca de la factibilidad de utilizar TAA en ancianos bajo distintas circunstancias, ni de su puesta en práctica en forma científica. Un equipo interdisciplinario de investigadores de la UBA (Psicología-Veterinaria) se propone un acercamiento al tema en diversos ámbitos: residencias privadas y públicas, hogares particulares y centros de jubilados y relata un avance preliminar en la investigación acerca del vínculo anciano-mascota, introduciendo una innovación original, ya que estudia las condiciones emocionales, sociales e institucionales que colocan este vínculo al servicio de la salud o al servicio de la patología. Además, aplica por primera vez y con una interpretación singular, una prueba específica en su batería de evaluación emocional: el ATAT. La presente investigación permitirá obtener ciertos impactos en el abordaje de la problemática de la tercera edad, tales como: mejor calidad de vida de los involucrados y moderación de las patologías en la vejez...

Clinical comparison of three different routes to laparoscopic adrenalectomy / 中国微创外科杂志

Ojective To research the appropriate routes the clinical results of the three different procedures for the laparoscopic adrenalectomy routes were compared. Methods Eighty six patients underwent laparoscopic adrenalectomy through three different routes-transperitoneal anterior (TAA), retroperitoneal lateral flank(RLA) and retroperitoneal posterior lumbar approaches(RPA). Results The time for performing operation through RPA and RLA was shorter than that through TAA(P

Vínculo anciano-mascota: condiciones y consecuencias. ¿Al servicio de la salud o al servicio de la patología? / Link elder-pet: conditions and consequences. In service of health or pathology service?

El punto de partida de esta investigación es explorar las posibilidades de aplicación en nuestro medio, con ancianos, de la llamada internacionalmente ¨Terapia Asistida por Animales¨ (TAA), como un enfoque interdisciplinario que implica la introducción de animales en la rutina de una persona, o grupo de personas, con fines terapéuticos. De acuerdo a este enfoque se considera que, si bien los animales por sí solos no ejercen un efecto terapéutico, pueden proveer estímulos que favorecen la terapia y la red social de apoyo. En Argentina no existen estudios acerca de la factibilidad de utilizar TAA en ancianos bajo distintas circunstancias, ni de su puesta en práctica en forma científica. Un equipo interdisciplinario de investigadores de la UBA (Psicología-Veterinaria) se propone un acercamiento al tema en diversos ámbitos: residencias privadas y públicas, hogares particulares y centros de jubilados y relata un avance preliminar en la investigación acerca del vínculo anciano-mascota, introduciendo una innovación original, ya que estudia las condiciones emocionales, sociales e institucionales que colocan este vínculo al servicio de la salud o al servicio de la patología. Además, aplica por primera vez y con una interpretación singular, una prueba específica en su batería de evaluación emocional: el ATAT. La presente investigación permitirá obtener ciertos impactos en el abordaje de la problemática de la tercera edad, tales como: mejor calidad de vida de los involucrados y moderación de las patologías en la vejez.

STUDY ON THE RELATION BETWEEN THE PRESENCE OF TUMOR ASSOCIATED ANTIGEN AND CTL PROLIFERATION AND CYTOLYTIC ACTIVITY WITH GASTRIC CARCINOMA / 肿瘤研究与临床

0. 001 ). Comparedwith the TAA negative group, much higher cytolytic activity was observed in the positive group (P

The Relevance of Degree of Liver Fibrosis, Ito cell, and PKC Activity in Hepatic Fibrogenesis / 대한간학회지

BACKGROUND/AIMS: Hepatic fibrosis in rat induced by thioacet amide shares similar morphological and biochemical characteristics with human liver cirrhosis. Thioacetamide (T AA) initially induces accumulation of collagen in Disse space and eventually leads to macro- and micronodular cirrhos is. Ito cell was believed to play a main role in hepatic fibrosis. And it s activity was known to be regulated by the expression of various genes. But little has been discovered about the upstream signal trans duction pathway of these genes in hepatic fibrosis. The expression of genesrelated to Ito cell activity was regulated by many transcription factors , the activity of which was regulated by protein kinase C( PKC) is oforms. So it is s upposed that PKC could be as s ociated with fibrosis in liver. METHODS: We investigated the correlation of PKC is oforms and It ocell activity in the course of hepatic fibrosis using TAA induced rat liver cirrhosis model. We used six week- old male rats , and administered 0.03% TAA in drinking water. The animals were sacrificed at 9, 20, and 30 weeks after TAA administration. The degree of hepatic fibrosis was evaluated by measuring the total amount of collagen.-SMA immunohist ochemical st aining of liver tissue was done to determine the Ito cell activity. The expression pattern of PKC isoforms was investigated by West ern blotting. RESULTS: In TAA- treated group, collagen cont ent and Ito cell activity did not increase until 30 weeks and 20 weeks of treatment , respectively, while in control group collagen cont ent and Ito cell activity were not detected. Collagen content showed linear correlation with Ito cell activity. This implied that the proliferation of activated Ito cells was prior to the increase of collagen content. In view of expression pattern of PKC is oforms, PKC alpha showed no difference in TAA- treated group and control group. In TAA-treated group, PKCbeta1 exhibited increased level of expression in both particulate and cytosolic forms at 9 weeks, while PKCdelta and PKC epsilon showed striking shift to particulated form. After 20 weeks, all of the PKC beta1, delta, and epsilon degenerated and showed remarkably decreased level of expression. This suggested PKC alpha had no relation to hepatic fibrosis,while PKC beta1, delta, and epsilon, showing activity at 9 weeks, were related to fibrosis og liver. In response to fibrogenic factors, molecules engaged in intracellular signal transduction pathway like PKC beta1, delta, and epsilon, began to change prior to the increase of Ito cell activity, morphologic changes and alterations of collagen content. CONCLUSION: Our results strongly suggest that the activity of PKC isoforms play an important role in early step of hepatic fibrosis, while accompanying Ito cell activity do in later step.