Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update

Large amounts of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2005. These include long-term follow-up studies in large community-based cohorts or asymptomatic subjects with chronic HBV infection, further studies on the role of HBV genotype/naturally occurring HBV mutations, treatment of drug resistance and new therapies. In addition, Pegylated interferon α2a, entecavir and telbivudine have been approved globally. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings were discussed and debated. The earlier “Asian-Pacific consensus statement on the management of chronic hepatitis B” was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, special indications for liver biopsy in patients with persistently normal alanine aminotransferase, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune-suppressive medications or chemotherapy and patients in the setting of liver transplantation, are also included

Two Estrogen Response Element Sequences Near the PCNA Gene Are Not Responsible for Its Estrogen-Enhanced Expression in MCF7 Cells

The proliferating cell nuclear antigen (PCNA) is an essential component of DNA replication, cell cycle regulation, and epigenetic inheritance. High expression of PCNA is associated with poor prognosis in patients with breast cancer. The 5'-region of the PCNA gene contains two computationally-detected estrogen response element (ERE) sequences, one of which is evolutionarily conserved. Both of these sequences are of undocumented cis-regulatory function. We recently demonstrated that estradiol (E2) enhances PCNA mRNA expression in MCF7 breast cancer cells. MCF7 cells proliferate in response to E2.Here, we demonstrate that E2 rapidly enhanced PCNA mRNA and protein expression in a process that requires ERalpha as well as de novo protein synthesis. One of the two upstream ERE sequences was specifically bound by ERalpha-containing protein complexes, in vitro, in gel shift analysis. Yet, each ERE sequence, when cloned as a single copy, or when engineered as two tandem copies of the ERE-containing sequence, was not capable of activating a luciferase reporter construct in response to E2. In MCF7 cells, neither ERE-containing genomic region demonstrated E2-dependent recruitment of ERalpha by sensitive ChIP-PCR assays.We conclude that E2 enhances PCNA gene expression by an indirect process and that computational detection of EREs, even when evolutionarily conserved and when near E2-responsive genes, requires biochemical validation

Effectiveness of bronchoscopic lung volume reduction using unilateral endobronchial valve: a systematic review and meta-analysis

Miyoung Choi,1 Worl Suk Lee,1 Min Lee,1 Kyeongman Jeon,2 Seungsoo Sheen,3 Sanghoon Jheon,4 Young Sam Kim5 1National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 3Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Republic of Korea; 4Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; 5Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea Background: Bronchoscopic lung volume reduction (BLVR) can be suggested as an alternative for surgical lung volume reduction surgery for severe emphysema patients. This article intends to evaluate by systematic review the safety and effectiveness of BLVR using a one-way endobronchial valve.Methods: A systematic search of electronic databases, including MEDLINE, EMBASE, and the Cochrane Library, as well as eight domestic databases up to December 2013, was performed. Two reviewers independently screened all references according to selection criteria. The Scottish Intercollegiate Guidelines Network criterion was used to assess quality of literature. Data from randomized controlled trials were combined and meta-analysis was performed. Results: This review included 15 studies. Forced expiratory volume in 1 second (FEV1) improved in the intervention group compared with the control group (mean difference [MD]=6.71, 95% confidence interval [CI]: 3.31–10.11). Six-minute walking distance (MD=15.66, 95% CI: 1.69–29.64) and cycle workload (MD=4.43, 95% CI: 1.80–7.07) also improved. In addition, St George’s Respiratory Questionnaire score decreased (MD=4.29, 95% CI: -6.87 to -1.71) in the intervention group. In a subgroup analysis of patients with complete fissure, the FEV1 change from baseline was higher in the BLVR group than in the control group for both 6 months (MD=15.28, P<0.001) and 12 months (MD=17.65, P<0.001), whereas for patients with incomplete fissure, FEV1 and 6-minute walking distance showed no change. One-year follow-up randomized controlled trials reported deaths, although the cause of death was not related to BLVR. Respiratory failure and pneumothorax incidence rates were relatively higher in the BLVR group, but the difference was not significant.Conclusion: BLVR may be an effective and safe procedure for the treatment of severe COPD patients with emphysema, based on existing studies. Keywords: endobronchial valve, bronchoscopic valve lung volume reduction, systematic review, meta-analysis&nbsp

Effects of nonylphenol, bisphenol A, and their mixture on the viviparous swordtail fish (Xiphophorus helleri)

A number of fish species have been used for studies on endocrine disrupting chemicals (EDCs). However, despite the widespread use of oviparous fish, relatively little attention has been given to viviparous species. This study investigated the effects of EDCs in a viviparous fish and examined the possible usefulness of the fish as an alternative model for the studies on EDCs. Swordtails (Xiphophorus helleri) were exposed to nonylphenol (NP), bisphenol A (BPA), and their mixture. Both short-term (3-d) and relatively long-term (60-d) exposures were carried out using adult male and 30-d-old juvenile fish, respectively. Following the short-term exposure, both NP and BPA caused vitellogenin mRNA expression. Flow cytometric analysis and terminal deoxynucleotidyl transferase assay on the testes of treated fish indicated reproductive damage. Histopathological analysis found degenerative and necrotic cells in seminiferous tubules following the exposure to 100 ppb NP. The testes with lesions were also associated with highly suppressed spermatogenesis. Following the long-term exposure, both NP and BPA exposures significantly affected the growth of swordtails. In all cases, the results showed that the mixture was always more potent than a single chemical and that swordtail fish can be a useful model for the study of endocrine disruptors