Changes in the gene expression associated with carbon tetrachloride-induced liver fibrosis persist after cessation of dosing in mice.

Recent studies have shown that gene expression profiles change in the livers of animals treated acutely with toxic chemicals such as carbon tetrachloride (CCl(4)). This study was undertaken to evaluate the changes in gene expression in mouse liver immediately after a long-term treatment with CCl(4) and possible effects of treatment cessation on these changes. Adult 129/Sv(pc)J mice were treated twice a week with CCl(4) at 1 ml/kg in olive oil for 4 weeks. Hepatic pathological changes observed in the CCl(4)-treated mice included necrosis, inflammation, and fibrosis, along with increased serum alanine aminotransferase activities. Consistent with these changes, expression of genes involved in cell death, cell proliferation, metabolism, DNA damage, and fibrogenesis were upregulated as detected by microarray analysis and confirmed by real-time RT-PCR. Four weeks after CCl(4) treatment cessation, the pathological changes were recovered, with the exception of fibrosis, which was not completely reversed. Most of the gene expression profiles also returned to the control level; however, the fibrogenetic genes remained at a high level of expression. These results demonstrate that changes in gene expression profile correlate with pathological alterations in the liver in response to CCl(4) intoxication. Most of these changes are recoverable upon withdrawal of the toxic insult. However, liver fibrosis is a prolonged change both in gene expression and histopathological alterations.     

阿米洛利的神经保护作用

阿米洛利是一种上皮细胞钠离子通道(ENaC)阻滞药,作为一种保钾利尿药已在临床应用了数十年.研究表明,中枢神经系统的多种离子通道对阿米洛利敏感,如酸敏感离子通道(ASIC)、Na+/H+交换泵等.这些通道具有重要的生理功能,而且还可能参与了脑缺血、组织酸中毒等病理学过程.阿米洛利通过阻滞这些通道,呈现出减轻缺血和酸化介导的神经元损伤等效应,很有可能成为治疗脑缺血等的新型神经保护剂.     

Antiviral activities of extracts isolated from Terminalis chebula Retz., Sanguisorba officinalis L., Rubus coreanus Miq. and Rheum palmatum L. against hepatitis B virus.

The antiviral effects of aqueous extracts of Terminalis chebula Retz., Sanguisorba officinalis L., Rubus coreanus Miq. and Rheum palmatum L. were examined by a cell culture system using a hepatitis B virus (HBV) producing cell line, HepG2 2.2.15. The extracts were assayed for the inhibition of HBV multiplication by measurement of HBV DNA and surface antigen (HBsAg) levels in the extracellular medium of HepG2 2.2.15 cells after an 8-day treatment. All extracts decreased the levels of extracellular HBV virion DNA at concentrations ranging from 64 to 128 microg/mL and inhibited the secretion of HBsAg dose dependently. Of the four tested plants, Terminalis chebula exhibited the most prominent anti-HBV activities.     

Inhibitory action of water soluble fraction of Terminalia chebula on systemic and local anaphylaxis

We investigated the effects of the water soluble fraction of Terminalia chebula (Combretaceae) (WFTC) on systemic and local anaphylaxis. WFTC administered 1h before compound 48/80 injection inhibited compound 48/80-induced anaphylactic shock 100% with doses of 0.01-1.0 g/kg. When WFTC was administered 5 or 10 min after compound 48/80 injection, the mortality also decreased in a dose-dependent manner. Passive cutaneous anaphylaxis was inhibited by 63.5+/-7.8% by oral administration of WFTC (1.0 g/kg). When WFTC was pretreated at concentrations ranging from 0.005 to 1.0 g/kg, the serum histamine levels were reduced in a dose-dependent manner. WFTC (0.01-1.0 mg/ml) also significantly inhibited histamine release from rat peritoneal mast cells (RPMC) by compound 48/80. However, WFTC (1.0 mg/ml) had a significant increasing effect on anti-dinitrophenyl IgE-induced tumor necrosis factor-alpha production from RPMC. These results indicate that WFTC may possess a strong antianaphylactic action.     

Expression of cyclooxygenase-2 in association with clinicopathological prognostic factors and molecular markers in epithelial ovarian cancer

OBJECTIVES: This study examines whether expression of COX-2 is associated with clinicopathological features and other molecular markers of ovarian cancer. METHODS: Sixty-four paraffin-embedded tissue specimens were obtained from patients with ovarian cancer who received cytoreductive surgery and combination chemotherapy. Tissue specimens were subjected to immunohistochemical analysis using antibodies to COX-2, p53, and VEGF. RESULTS: Increased COX-2 expression significantly correlated with histologic type (mucinous 5.6% vs. non-mucinous 65.2%, P<0.001). COX-2 expression was also significantly associated with stage, tumor grade, residual disease status, and presence of ascites. COX-2 expression correlated positively with expression of p53 (P=0.006) and VEGF (P=0.025). Although survival was lower in patients with high COX-2 expression than in those without high COX-2 expression (P<0.001), only tumor grade and stage were independent prognostic indicators. In patients with non-mucinous cancer, COX-2 expression correlated with stage (P<0.001) and presence of ascites (P=0.033). CONCLUSIONS: Our results suggest that expression of COX-2 in ovarian cancers is specific to histologic type of tumor and is associated with poor clinicopathologic prognostic factors. Expression of COX-2 also correlates well with expression of p53 and VEGF.     

Venous Thromboembolism Risk in Asian Patients with Inflammatory Bowel Disease: A Population-Based Nationwide Inception Cohort Study

Background/AimsInflammatory bowel disease (IBD) is associated with the occurrence of venous thromboembolism (VTE). However, to date, there have been few studies on the risk of VTE in Asian IBD patients. We aimed to estimate the incidence of VTE in Asian IBD patients and to determine if IBD is related to increased VTE risk.MethodsWe performed a population-based cohort study between 2004 and 2015 using Korean National Health Insurance data. IBD and VTE were defined by ICD-10 codes. Incidence rates of VTE were calculated among patients with IBD and among age- and sex-matched controls. Hazard ratios were estimated using Cox regression with adjustment for multiple variables. We performed additional analyses stratifying by age, sex, Charlson comorbidity index (CCI) score, and disease type.ResultsAmong the 45,037 patients with IBD (IBD cohort) and 133,019 matched controls (non-IBD cohort) included in our analysis, 411 IBD patients and 641 controls developed VTE. The IBD cohort had a higher incidence rate ratio and risk of VTE than the non-IBD cohort (incidence rate ratio 1.92 and hazard ratio 1.93). Older age, female sex, higher CCI scores, cardiovascular disease, chronic kidney disease, use of steroids, and hospitalization were significant risk factors for VTE in patients with IBD.ConclusionsThe IBD patients in this study were approximately two times more likely to develop VTE than the non-IBD individuals. Our findings support the need for thromboprophylaxis in Asian IBD patients with various factors that further increase the risk of VTE.     

Association between metabolic syndrome and left ventricular geometric change including diastolic dysfunction

BackgroundWe investigated the association between individual components of metabolic syndrome (MetS) and left ventricular (LV) geometric changes, including diastolic dysfunction, in a large cohort of healthy individuals.MethodsOverall, 148 461 adults who underwent echocardiography during a health‐screening program were enrolled. Geographic characteristics on echocardiography and several markers of LV relaxation function were identified according to individual MetS components. Univariate linear regression analysis and a multivariate regression model adjusted for factors known to influence LV relaxation function were conducted.ResultsThe prevalence of LV diastolic dysfunction (LVDD) was higher in the MetS group than in the non‐MetS group (0.56% vs. 0.27%, p < .001). In univariate and multivariate analyses, E/A ratio, e′ velocity, and left atrial volume index were significantly associated with each component of MetS and covariates (all p ≤ .001). In the age‐ and sex‐adjusted model, MetS was significantly associated with LVDD (odds ratio [95% confidence interval], 1.350 [1.103, 1.652]). However, subjects with more MetS components did not have a significantly higher risk of LVDD. As the analysis was stratified by sex, the multivariate regression model showed that MetS was significantly associated with LVDD only in men (1.3 [1.00, 1.68]) with higher risk in more MetS component (p for trend < .001). In particular, triglyceride (TG) and waist circumference (WC) among MetS components were significantly associated with LVDD in men.ConclusionsMetS was associated with the risk of LVDD, especially in men, with a dose‐dependent association between an increasing number of components of MetS and LVDD. TG and WC were independent risk factors for LVDD in men.