RESUMO
INTRODUCTION AND OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) is often accompanied by fetal and maternal complications. MATERIALS AND METHODS: Retrospective review of the clinical course of women with ICP and their neonates treated at our medical center over a 10-year period. Special attention was paid to the maternal and neonatal response to 2 different modes of ursodeoxycholic acid (UDCA) administration. RESULTS: Neonates of mothers with high total bile acid levels had a poorer composite neonatal outcome. Twenty-seven women who presented at an advanced stage of their pregnancies did not receive UDCA. UDCA was administered in 2 modes: either a full dose at admission (76 women) or a gradually increasing dose until the desired dosage was reached (25 women). The mean gestational age at delivery for the 94 neonates that were exposed to full UDCA dose was the lowest (36±2.3 weeks for the full dose, 37±1.4 weeks for the 30 neonates from the gradually increasing dose, 38±1.6 weeks for the 29 neonates from the no treatment group, p<0.001). The group of neonates that were exposed to full UDCA dose had the highest rate of unfavorable composite neonatal outcome (53% for full dose, 30% for gradually increasing dose, 24% for the no treatment group, p=0.006). CONCLUSIONS: Compared to the administration of a full UDCA dose, the administration of a gradually increasing dose of UDCA may be associated with a greater gestational age at delivery and fewer events of unfavorable composite neonatal outcomes. These novel findings should be retested prospectively in a large cohort of patients.
Assuntos
Colagogos e Coleréticos , Colestase Intra-Hepática , Idade Gestacional , Complicações na Gravidez , Ácido Ursodesoxicólico , Humanos , Ácido Ursodesoxicólico/administração & dosagem , Ácido Ursodesoxicólico/uso terapêutico , Feminino , Gravidez , Colestase Intra-Hepática/tratamento farmacológico , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/sangue , Estudos Retrospectivos , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/sangue , Recém-Nascido , Colagogos e Coleréticos/administração & dosagem , Colagogos e Coleréticos/efeitos adversos , Colagogos e Coleréticos/uso terapêutico , Adulto , Resultado do Tratamento , Resultado da GravidezRESUMO
BACKGROUND: Signet ring cell carcinoma (SRCC) is classified as an undifferentiated gastric carcinoma with poor prognosis. Early SRCCs are associated with improved prognosis. OBJECTIVES: To describe the outcomes of incidental SRCC. METHODS: In this case series, 900 medical charts of patients with SRCC were screened to identify patients with incidental SRCC, defined as diagnosed in random, non-focal-lesion-targeted biopsies. RESULTS: Six patients were diagnosed with incidental SRCC and underwent gastrectomy. The final pathology of five patients revealed one or more small foci of early SRCC without lymphovascular invasion. Only one patient had no evidence of malignancy. The median follow-up after surgery was 4.2 years (50 months, range 37-90 months). No deaths or recurrences were recorded during the follow-up period. These results resemble the reported survival rate for early SRCC. CONCLUSIONS: An aggressive surgical approach in incidental gastric SRCC patients is recommended, as they have a chance for long-term survival.
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BACKGROUND: Since the implementation of a hepatitis A virus (HAV) immunization program for children, which began in 1999 in Israel, HAV infections in the country have occurred mostly in adults. HAV infection in adults is usually symptomatic and may present with hepatic, as well as extrahepatic, abdominal complications. OBJECTIVES: To estimate the prevalence of extrahepatic abdominal complications in patients diagnosed with HAV. METHODS: Most extrahepatic abdominal complications corresponding to HAV infection have ultrasonographic manifestations; therefore, we retrospectively collected findings from ultrasound examinations in addition to laboratory data from adult patients with HAV infection who were admitted to our medical center between 2004 and 2016. Associations between ultrasonographic findings and laboratory parameters that reflect disease severity were identified. RESULTS: A total of 43 consecutive adult patients were included in this study. None presented with fulminant hepatic failure. Thirty patients (70%) had at least one ultrasonographic finding. Ascites was noted in 8 patients, a thickened gallbladder wall was observed in 14, pericholecystic fluid was found in 8, and biliary sludge was observed in 4. Significant associations included the presence of any ultrasonographic finding and peak total bilirubin levels (P = 0.021), the presence of ascites with peak aspartate and alanine aminotransferase levels (P = 0.041 and P = 0.038, respectively), and the presence of biliary sludge and nadir albumin during the HAV disease course (P = 0.037). CONCLUSIONS: Abdominal ultrasonographic findings, such as ascites and gallbladder abnormalities, are frequently observed during acute HAV infection and are significantly associated with disease severity.
Assuntos
Ascite/epidemiologia , Doenças da Vesícula Biliar/epidemiologia , Hepatite A/complicações , Adolescente , Adulto , Idoso , Ascite/etiologia , Feminino , Vesícula Biliar/diagnóstico por imagem , Vesícula Biliar/patologia , Doenças da Vesícula Biliar/etiologia , Vírus da Hepatite A , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Ultrassonografia/métodos , Adulto JovemRESUMO
BACKGROUND: In developed countries, hepatitis A virus (HAV) infection occurs mainly in adults. It is usually symptomatic and may cause acute liver failure (ALF). In patients with chronic liver disease, serum ferritin levels (SFL) can predict short-term prognosis. OBJECTIVES: To determine whether admission SFL can serve as a prognostic marker in patients with HAV infection. METHODS: A retrospective analysis of 33 adults with HAV infection was conducted. Because none of our patients presented with ALF, the parameter "length of hospital stay," was used as a surrogate marker of disease severity. RESULTS: The mean (± SD) at admission SFL was 2529 ± 4336 ng/ml. SFL correlated with the levels of international normalized ratio (INR), liver enzymes, and degree of hemolysis that occurred during the disease course. SFL did not correlate with the levels of either albumin or bilirubin or with the length of the hospital stay. The mean length of hospital stay was 5.1 ± 2.0 days, which correlated with the levels of INR, albumin, and bilirubin as well as the degree of hemolysis. However, in multivariate analysis only albumin and bilirubin predicted the length of the hospital stay. Follow-up SFL, which were available only in eight patients, decreased during the hospital stay. CONCLUSIONS: In adults with acute HAV infection, SFL may be increased. SFL correlated with the degree of liver injury and hemolysis that occur during the disease. However, in our cohort of HAV patients, who had a relatively benign disease course, SFL were of no prognostic value.
Assuntos
Ferritinas/sangue , Hepatite A/sangue , Avaliação de Resultados da Assistência ao Paciente , Adolescente , Adulto , Idoso , Feminino , Hepatite A/complicações , Humanos , Israel , Tempo de Internação/estatística & dados numéricos , Falência Hepática Aguda/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND AND AIMS: Rats are resistant to acetaminophen (APAP) hepatotoxicity. In this study, we evaluated whether by augmentation of the hepatic oxidative stress, through the induction of hepatic iron overload (IO), it will be feasible to overcome the resistance of rats to the toxic effects of APAP. METHOD: Rats with no or increased hepatic IO. RESULTS: Providing iron by diet induced hepatocellular IO, while parenteral iron administration induced combined hepatocellular and sinusoidal cell IO. APAP administration to rats with no IO caused an increase in hepatic oxidative stress and a decrease in the hepatic antioxidative markers but no hepatic cell damage. APAP administration to rats with hepatocellular IO further amplified the hepatic oxidative stress but induced only hepatocyte feathery degeneration without any increase in serum aminotransaminases. APAP administration to rats with combined hepatocellular and sinusoidal cell IO caused an unexpected decrease in hepatic oxidative stress and increase in the hepatic antioxidative markers and no hepatic cell damage. No hepatic expression of activated c-jun-N-terminal kinase was detected in any of the rats. CONCLUSIONS: The hepatic distribution of iron may affect its oxidative/antioxidative milieu. Augmentation of hepatic oxidative stress did not increase the rats' vulnerability to APAP.
Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Sobrecarga de Ferro/metabolismo , Ferro/metabolismo , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Acetaminofen/administração & dosagem , Doença Aguda , Animais , Antioxidantes/metabolismo , Overdose de Drogas/metabolismo , Fígado/metabolismo , Testes de Função Hepática , Masculino , Ratos Sprague-DawleyRESUMO
BACKGROUND: We recently observed patients with chronic liver disease (CLD) or chronic reflux symptoms (CRS) who developed gastric polyps (GPs) while undergoing surveillance gastroscopies for the detection of esophageal varices or Barrett's esophagus, respectively. OBJECTIVES: To identify risk factors for GP growth and estimate its growth rate. METHODS: GP growth rate was defined as the number of days since the first gastroscopy (without polyps) in the surveillance program, until the gastroscopy when a GP was discovered. RESULTS: Gastric polyp growth rates in CLD and CRS patients were similar. However, hyperplastic gastric polyps (HGPs) were detected more often (87.5% vs. 60.5%, P = 0.051) and at a higher number (2.57 ± 1.33 vs. 1.65 ± 0.93, P = 0.021) in the CLD patients. Subgroup analysis revealed the following findings only in CLD patients with HGPs: (i) a positive correlation between the GP growth rate and the patient's age; the older the patient, the higher the GP growth rate (r = 0.7, P = 0.004). (ii) A negative correlation between the patient's age and the Ki-67 proliferation index value; the older the patient, the lower the Ki-67 value (r = -0.64, P = 0.02). No correlation was detected between Ki-67 values of HGPs in CLD patients and the presence of portal hypertension, infection with Helicobacter pylori, or proton pump inhibitor use. CONCLUSIONS: In comparison with CRS patients, CLD patients developed HGPs more often and at a greater number. Young CLD patients may have a tendency to develop HGPs at a faster rate than elderly CLD patients.
Assuntos
Pólipos Adenomatosos , Refluxo Gastroesofágico/complicações , Gastroscopia/métodos , Hepatopatias/complicações , Neoplasias Gástricas , Pólipos Adenomatosos/patologia , Pólipos Adenomatosos/fisiopatologia , Fatores Etários , Idoso , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/etiologia , Progressão da Doença , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Feminino , Infecções por Helicobacter/epidemiologia , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Neoplasias Gástricas/fisiopatologia , Fatores de TempoRESUMO
BACKGROUND: Genetic factors implicated in the pathogenesis of non-alcoholic fatty liver disease are poorly understood. Our aim was to characterize three genes involved in a rat model of non-alcoholic fatty liver disease and investigate the effect of rosiglitazone and bezafibrate. METHOD: Five rats were fed a chow diet (controls) and 18 a fructose-enriched diet (FED) for 5 weeks: 6 were administered rosiglitazone and 6 bezafibrate during the last 2 weeks and 6 were not treated at all. Livers were examined by reverse transcription-PCR for the genes encoding peroxisome proliferator-activated receptors (PPAR), PPAR-α, PPAR-γ, and Mn superoxide dismutase2 (Mn SOD2). Western blot was used for proteins levels. RESULT: The FED rats showed a decrease in mRNA of MnSOD2, PPAR-α, and PPAR-γ (3, 3.5 fold, and 27%, respectively) (p<0.05). The 3 genes normalized in response to rosiglitazone and bezafibrate. The proteins of MnSOD2, PPAR-α and PPAR-γ in the FED rats decreased (2.5, 2, and 2.2, respectively) (p<0.05). Following administration of rosiglitazone, proteins of MnSOD2, PPAR-α and PPAR-γ in the FED rats increased (reaching 1.5-fold, a 20% increase and normalization, respectively), (p<0.05). Administration of bezafibrate to the FED rats restored the proteins of 3 genes to baseline. CONCLUSION: A consistent reduction in hepatic expression of MnSOD2, PPAR-α and PPAR-γ in the FED rats compared with controls was observed. Administration of either rosiglitazone or bezafibrate to the FED rats restored these genes to a pre-morbid state.
Assuntos
Bezafibrato/farmacologia , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/genética , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Fígado/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Animais , Modelos Animais de Doenças , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/patologia , Frutose , Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Ratos , Ratos Sprague-Dawley , Rosiglitazona , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND AND AIM: Variation in the prevalence of various types of gastric polyps worldwide may reflect different etiologies. Here, the authors report the dynamic changes in histological distribution of gastric polyps over time and by ethnicity for individuals who underwent gastroscopies between 1994 and 2009 at two hospitals in Jerusalem, Israel. During this time period, the proportion of patients receiving proton pump inhibitors (PPIs) increased while the proportion of patients infected with Helicobacter pylori (H. pylori) decreased. PATIENTS AND METHODS: Pathological reports of biopsies from 50,071 consecutive gastroscopies were reviewed. RESULTS: Gastric polyps were detected in 727 individuals. The yearly prevalence of gastric polyps was ≤ 1% between 1994 and 2001 and ≥ 2% from 2004 to 2009, of which overall 66% were hyperplastic polyps and 23% fundic gland polyps (FGPs). FGPs were diagnosed exclusively in the Jewish population. From 2001 to 2004, an increase in the absolute number of newly discovered hyperplastic and FGPs per year was observed. However from 2005, a divergent trend of changes was observed: While the proportion of patients with hyperplastic polyps dropped from 0.72 during the 2001-2004 period to 0.62 during the 2005-2009 period (p = 0.02), the proportion of patients with FGPs at these time periods increased from 0.16 to 0.33 (p = 0.0001). CONCLUSIONS: The yearly prevalence of gastric polyps in Jerusalem has recently doubled. This occurred mainly due to the increasing prevalence of FGPs. The changing epidemiology of gastric polyps is probably related to the interaction between genetic factors and fluctuating environmental factors like H. pylori infection rates and exposure to PPIs.
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Pólipos/etnologia , Pólipos/patologia , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Intervalos de Confiança , Endoscopia Gastrointestinal , Feminino , Gastrite/epidemiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Humanos , Incidência , Israel/epidemiologia , Judeus/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pólipos/epidemiologia , Prevalência , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Fatores Sexuais , Neoplasias Gástricas/epidemiologiaRESUMO
Ascites is the most common manifestation of decompensated liver cirrhosis. The life expectancy of cirrhotic patients developing uncomplicated ascites is 50% for 3 years. Refractory ascites, electrolyte imbalance, hepato-renal syndrome and spontaneous bacterial peritonitis may develop. Successful treatment can improve symptoms and outcomes. This article summarizes the Israeli Association for the Study of the Liver guidelines for diagnosis and management of cirrhotic ascites and its complications.
Assuntos
Ascite/terapia , Cirrose Hepática/terapia , Ascite/complicações , Ascite/diagnóstico , Humanos , Israel , Expectativa de Vida , Cirrose Hepática/complicações , Cirrose Hepática/diagnósticoRESUMO
An increase in serum ferritin levels during combined interferon-ribavirin treatment in chronic patients infected with hepatitis C virus (HCV) can occur. A study was conducted to determine whether observing the kinetics of serum ferritin levels during antiviral therapy, may assist in predicting the rate of sustained virological response. The kinetics of serum ferritin levels during antiviral therapy in treatment-naive, adherent patients with chronic HCV who had early virological response were characterized. Thirteen patients achieved sustained virological response (group 1) while eight patients did not (group 2). Pre-treatment serum ferritin levels were higher in group 2 patients. During antiviral therapy, serum ferritin levels increased in both groups. On treatment, the median increase (compared to baseline) and the calculated rate of the increase in serum ferritin levels was higher in group 1 patients (874% vs. 272%, P < 0.05, 63%/week vs. 13%/week, P = 0.024, respectively). Red blood cell lysis did not contribute to the increase in serum ferritin level. Post-treatment (1st month) serum ferritin levels in group 1 patients were lower than in group 2 patients. In addition, the degree of decline in the 1st month serum ferritin levels (from peak levels) in group 1 patients was higher (76% vs. 49%, P = 0.039). Measuring serum ferritin levels during antiviral therapy in HCV patients who had an early virological response may assist in predicting sustained virological response.
Assuntos
Antivirais/administração & dosagem , Ferritinas/sangue , Hepatite C Crônica/tratamento farmacológico , Fígado/virologia , Adulto , Biópsia , Quimioterapia Combinada/métodos , Feminino , Ferritinas/biossíntese , Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Prognóstico , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina/administração & dosagem , Carga ViralAssuntos
Abscesso/etiologia , Colite Ulcerativa/complicações , Linfonodos/patologia , Esplenopatias/etiologia , Abscesso/diagnóstico por imagem , Adulto , Colite Ulcerativa/fisiopatologia , Humanos , Linfonodos/diagnóstico por imagem , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Índice de Gravidade de Doença , Esplenopatias/diagnóstico por imagemRESUMO
BACKGROUND: The success of Helicobacter pylori (H. pylori) eradication depends on several host and treatment factors. Serum vitamin D levels may be associated with H. pylori infection and eradication rates. We investigated the association between vitamin D and H. pylori infection and eradication, using a large electronic database based on medical records from a population-based health maintenance organization. METHODS: Data regarding adults who underwent H. pylori testing and had vitamin D measurements within one month of H. pylori testing were collected. H. pylori infection was ascertained using urea breath or stool antigen tests. A negative H. pylori test following a positive result implied eradication. Multivariate regression models were constructed to assess associations between H. pylori infection, eradication, and vitamin D. RESULTS: Among 150,483 members who underwent H. pylori testing from 2009 to 2018, 27,077 (18%) had vitamin D measurements. Vitamin D levels were inversely associated with H. pylori infection, p < 0.001. The odds of a positive H. pylori test were 31% higher among patients with vitamin D levels <20 ng/mL, compared with those with levels ≥20 ng/mL (OR 1.31, 99% CI 1.22-1.4, p < 0.001). Purchase of vitamin D supplements was associated with a negative subsequent H. pylori test (p < 0.001). Mean vitamin D levels were moderately higher in those with successful vs. failed H. pylori eradication (19.34 ± 9.55 vs. 18.64 ± 9.61, p < 0.001). CONCLUSIONS: Vitamin D levels are associated with H. pylori infection. Increased vitamin D levels are associated with successful H. pylori eradication. Vitamin D may have a role in H. pylori eradication.
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Infecções por Helicobacter/sangue , Helicobacter pylori/isolamento & purificação , Vitamina D/sangue , Adulto , Suplementos Nutricionais , Feminino , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Vitamina D/administração & dosagemRESUMO
BACKGROUND AND AIM: Controversy exists as to whether rats after bile duct ligation (BDL) are more susceptible to gastric mucosal damage (GMD) induced by irritants. In the present study we characterize GMD after intragastric instillation of either ethanol or hydrochloric acid (HCL), 3 and 21 days after the surgical procedure. METHODS: Bile duct ligation and sham operated (SO) rats were studied. RESULTS: Three days after surgery, BDL rats exhibited a reduction in gastric mucosal nitric oxide synthase (NOS) activity but an increase in ethanol-induced GMD. Twenty-one days after surgery gastric mucosal prostaglandin (PG) E(2) generation in BDL rats was increased while NOS activity in both groups was similar. Ethanol-induced GMD in SO rats was higher. Pretreatment with NG-nitro-L-arginine methyl ester, prior to ethanol administration was associated with an increase in gastric mucosal PGE(2) generation: (147% in SO and 104% in BDL rats) and in GMD (176% in SO and 303% in BDL rats). HCL induced GMD was of similar magnitude in both groups in both time periods. CONCLUSIONS: The gastric resistance to damage by irritants in rats with BDL is not a static phenomenon. This may result from sequential changes that occur in the gastric mucosal defense mechanisms during the evolution of liver disease.
Assuntos
Colestase Extra-Hepática/complicações , Ducto Colédoco/cirurgia , Dinoprostona/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Irritantes/toxicidade , Óxido Nítrico/metabolismo , Gastropatias/etiologia , Animais , Colestase Extra-Hepática/metabolismo , Colestase Extra-Hepática/fisiopatologia , Modelos Animais de Doenças , Progressão da Doença , Etanol/administração & dosagem , Etanol/toxicidade , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Ácido Clorídrico/administração & dosagem , Ácido Clorídrico/toxicidade , Instilação de Medicamentos , Irritantes/administração & dosagem , Ligadura , Masculino , Óxido Nítrico/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Gastropatias/metabolismo , Gastropatias/patologiaRESUMO
BACKGROUND/AIMS: The endocannabinoid system in mice plays a role in models of human cirrhosis and hepatic encephalopathy (HE), induced by a hepatotoxin. We report now the therapeutic effects of cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, on HE caused by bile duct ligation (BDL), a model of chronic liver disease. METHODS: CBD (5mg/kg; i.p.) was administered over 4weeks to mice that had undergone BDL. RESULTS: Cognitive function in the eight arm maze and the T-maze tests, as well as locomotor function in the open field test were impaired by the ligation and were improved by CBD. BDL raised hippocampal expression of the TNF-alpha-receptor 1 gene, which was reduced by CBD. However, BDL reduced expression of the brain-derived neurotrophic factor (BDNF) gene, which was increased by CBD. The effects of CBD on cognition, locomotion and on TNF-alpha receptor 1 expression were blocked by ZM241385, an A(2)A adenosine receptor antagonist. BDL lowers the expression of this receptor. CONCLUSIONS: The effects of BDL apparently result in part from down-regulation of A(2)A adenosine receptor. CBD reverses these effects through activation of this receptor, leading to compensation of the ligation effect.
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Canabidiol/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Transtornos Neurológicos da Marcha/tratamento farmacológico , Transtornos Neurológicos da Marcha/etiologia , Encefalopatia Hepática/complicações , Hepatopatias/complicações , Antagonistas do Receptor A2 de Adenosina , Animais , Ductos Biliares/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Canabidiol/farmacologia , Doença Crônica , Cognição/efeitos dos fármacos , Cognição/fisiologia , Transtornos Cognitivos/metabolismo , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Feminino , Transtornos Neurológicos da Marcha/metabolismo , Encefalopatia Hepática/etiologia , Ligadura/efeitos adversos , Hepatopatias/etiologia , Camundongos , Camundongos Endogâmicos , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , RNA Mensageiro/metabolismo , Receptor A2A de Adenosina/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Resultado do Tratamento , Triazinas/farmacologia , Triazóis/farmacologiaRESUMO
BACKGROUND & AIMS: Reduced bone mass and increased fracture rate are complications of primary biliary cirrhosis (PBC). The effect of intermittent administration of human parathyroid hormone (hPTH) 1-34 on bone mass and architecture in bile duct-ligated (BDL) rats was studied. METHODS: Six-month-old male rats were subjected to BDL or sham operation (SO) and were treated from the second postoperative week intermittently with either hPTH 1-34 40 microg/kg per day, 80 microg/kg per day, or a vehicle for 4 weeks. Femoral and tibial bones were evaluated ex vivo by dual x-ray absorptiometry, microcomputed tomography, and histomorphometry. Serum osteocalcin and urinary deoxypyridinoline cross-links (DPD) were determined. RESULTS: BDL rats had decreased bone mass compared with SO rats as indicated by a 6% decrease in femoral and tibial bone mineral density (BMD), 18% reduction in femoral trabecular bone volume (bone volume/total volume [BV/TV]), 17% decrease in trabecular thickness, and 10% decrease in tibial cortical thickness. The administration of hPTH 1-34 at 40 microg/kg per day increased femoral and tibial BMD (9% and 9%), femoral trabecular BV/TV (50%), trabecular thickness (50%), tibial cortical thickness (17%), and serum osteocalcin (82%). On the other hand, hPTH 1-34 80 microg/kg per day had no effect on BMD and tibial cortical thickness, was associated with a smaller increase in trabecular BV/TV (24%), and had a higher osteoclast number and DPD compared with untreated BDL rats and the lower hPTH 1-34 dose treatment group. CONCLUSIONS: BDL rats exhibit loss of bone mass and structure, which can be prevented by the intermittent administration of hPTH 1-34, a potential therapy for osteoporosis in PBC.
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Conservadores da Densidade Óssea/uso terapêutico , Cirrose Hepática Biliar/complicações , Osteoporose/etiologia , Osteoporose/prevenção & controle , Teriparatida/uso terapêutico , Animais , Densidade Óssea , Remodelação Óssea/fisiologia , Modelos Animais de Doenças , Fêmur , Humanos , Cirrose Hepática Biliar/fisiopatologia , Masculino , Ratos , TíbiaRESUMO
BACKGROUND/AIM: Changes in tissue levels of 2-arachidonoylglycerol (2-AG), an endocannabinoid, during the evolution of bile duct ligation (BDL) may indicate that endocannabinoids have a role in the hemodynamic changes that occur in this condition. METHODS: 2-AG levels, in various organs and vascular beds of BDL rats, 2 and 4 weeks post surgery, were determined. Untouched and sham-operated (SO) rats were used as controls. RESULTS: 2-AG content of a specific organ was not a static finding and depended on the rat's age, the time from the surgical procedure and the type of procedure. The most pronounced changes were observed in BDL rats 4 weeks post surgery. In these rats, hepatic, pulmonary, cardiac and renal medullary and papillary 2-AG levels were highest observed. No changes in splenic, aortic and renal cortical 2-AG levels were observed. In addition a stepwise increase in 2-AG levels from the cortex to the papilla was detected and was followed by a decrease in creatinine clearance. CONCLUSIONS: 2-AG probably has a role in the pathophysiologic changes in the liver, heart, lung and kidney that follows BDL.