Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis C

INTRODUCTION The goal of therapy for chronic hepatitis C (CHC) is the eradication of the hepatitis C virus (HCV)[1]. In the recent decade, anti-viral therapy against HCV has been markedly improved, especially treatment with ribavirin and peg- interferon (…     

International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.

Non-inflammatory cystic lesions of the pancreas are increasingly recognized. Two distinct entities have been defined, i.e., intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). Ovarian-type stroma has been proposed as a requisite to distinguish MCN from IPMN. Some other distinct features to characterize IPMN and MCN have been identified, but there remain ambiguities between the two diseases. In view of the increasing frequency with which these neoplasms are being diagnosed worldwide, it would be helpful for physicians managing patients with cystic neoplasms of the pancreas to have guidelines for the diagnosis and treatment of IPMN and MCN. The proposed guidelines represent a consensus of the working group of the International Association of Pancreatology.     

Hypertension Due to Loss of Clock: Novel Insight From the Molecular Analysis of <Emphasis Type="Italic">Cry1</Emphasis>/<Emphasis Type="Italic">Cry2</Emphasis>–Deleted Mice

In our consumer-oriented society, in which productivity requires around-the-clock activity and demanding shift work, the biologic system that regulates our internal rhythms is being compromised. Poor sleep patterns and hectic lifestyle are detrimental to harmonious physiological and metabolic body systems, with severe impact on public health. Over a trillion peripheral cellular clocks throughout the body, supervised by the master clock located in the hypothalamic suprachiasmatic nucleus, govern most aspects of physiology and behavior. To exemplify the importance of the biologic clock for health, we have recently demonstrated that mice that are arrhythmic because of the deletion of Cry1 and Cry2 clock genes suffer from salt-sensitive hypertension. In these mice, a novel 3β-hydroxyl-steroid dehydrogenase (3β–Hsd) gene under clock control is severely overexpressed specifically in aldosterone-producing cells in the adrenal cortex, leading to hyperaldosteronism and ultimately to salt-sensitive hypertension. The human homologue of this aldosterone-producing, cell-specific enzyme was also characterized and represents a new possibility in the pathogenesis of hypertension.     

Three-dimensional two-layer collagen matrix gel culture model for evaluating complex biological functions of monocyte-derived dendritic cells

Dendritic cell-like cells (Mo-DCs) generated from peripheral blood monocytes with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used as tools to treat cancer patients (DC-vaccines). Because Mo-DCs have multiple antigen presentation-related functions, including phagocytosis, migration, cytokine production, and T cell stimulation, establishment of a method for simultaneously evaluating the various functions of Mo-DCs is important. We developed a new in vitro three-dimensional two-layer collagen matrix culture model that consists of a collagen gel containing Mo-DCs as the lower layer and a collagen gel containing necrotic GCTM-1 tumor cells and/or T cells as the upper layer. We used this system to observe simultaneously multiple functions of Mo-DCs by phase-contrast or fluorescence microscopy and to assess IL-12 secretion during more than 2 weeks of culture. We also observed interactions between Mo-DCs and necrotic GCTM-1 or T cells on an individual cell basis by time-lapse videomicroscopy. In addition, we collected Mo-DCs from the collagen gels by collagenase treatment and analyzed the expression of antigen presentation-related molecules such as HLA-DR, CD80, CD83, and CD86 on Mo-DCs. This model may be a useful tool for evaluation of the various functions of Mo-DCs used as DC vaccines and for studies of the complex behaviors of Mo-DCs in vivo.     

Rapid detection of the hepatitis B virus YMDD mutant using TaqMan-minor groove binder probes

BACKGROUND: TaqMan-minor groove binder (MGB) probes were used in a real-time PCR-based assay for the rapid and accurate detection of hepatitis B virus (HBV) YMDD mutants. METHODS: TaqMan-MGB probes were designed to distinguish between wild-type (YMDD) and mutant (YVDD and YIDD) strains of HBV. The detection limit and sensitivity of the assay were determined using a dilution series of a mixture of wild-type and mutant plasmids. Serum samples collected from four patients with chronic mutant HBV infections during lamivudine therapy were analyzed using this method. RESULTS: The detection limit for YVDD and YIDD was 10 and 50 copies, respectively, whereas the sensitivity was 10% within a mixed virus population. In the clinical samples, mutant strains of HBV could be detected at levels <2.6 log copies/ml of HBV DNA. While 15 of the 21 samples tested by this method were positive for the YMDD mutant, direct sequencing and a reverse hybridization line probe assay (INNO-LiPA HBV DR v2) detected the mutant strain in only 11 and 9 samples, respectively. Moreover, the data for 6 samples analyzed by TA cloning were fully consistent with our TaqMan PCR results. CONCLUSIONS: We successfully established a sensitive and accurate assay for the YMDD mutant of HBV. This method may be useful for monitoring patients treated with lamivudine.     

Neuroprotective effects of group II metabotropic glutamate receptor agonist DCG-IV on hippocampal neurons in transient forebrain ischemia

Activation of group II metabotropic glutamate receptor (mGluR) inhibits the excessive release of glutamate that may be crucial in the pathogenesis of cerebral ischemia. This study investigated the protective effects of the group II mGluR agonist (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IV), against cerebral ischemia by examining extracellular glutamate concentration ([Glu]e) and neuronal damage in a rat model of transient forebrain ischemia. Cerebral ischemia was induced by 5 min of bilateral carotid artery occlusion and hypotension. DCG-IV (10, 100, or 250 pmol) was administered into the lateral ventricle four times every 12 h from 36 h before the start of ischemia, or administered intraperitoneally (40 μmol/kg) 24 h before ischemia, and the effect of the group II mGluR antagonist (LY341495) was also examined. [Glu]e in the CA1 subfield was measured by microdialysis during the peri-ischemic period, and the survival rate of CA1 neurons was evaluated 5 days after ischemia. [Glu]e increased significantly after cerebral ischemia and reached the maximum at 1 min after reperfusion, then gradually decreased and returned to the preischemic level in the vehicle group. The intraventricular injection of DCG-IV (250 pmol) significantly attenuated the [Glu]e increase and significantly increased the survival rate of CA1 neurons. Co-injection of LY341495 reversed the protective effects of DCG-IV. These results suggest that pretreatment with DCG-IV has neuroprotective effects against ischemic neuronal injuries through the inhibition of the glutamate release via the activation of group II mGluR.     

Current characteristics and management of ST elevation and non-ST elevation myocardial infarction in the Tokyo metropolitan area: from the Tokyo CCU network registered cohort

Limited data exists on ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) managed by a well-organized cardiac care network in a metropolitan area. We analyzed the Tokyo CCU network database in 2009–2010. Of 4329 acute myocardial infarction (AMI) patients including STEMI (n = 3202) and NSTEMI (n = 1127), percutaneous coronary intervention (PCI) was performed in 88.8 % of STEMI and 70.4 % of NSTEMI patients. Mean onset-to-door and door-to-balloon times in STEMI patients were shorter than those in NSTEMI patients (167 vs 233 and 60 vs 145 min, respectively, p < 0.001). Coronary artery bypass graft surgery was performed in 4.2 % of STEMI and 11.4 % of NSTEMI patients. In-hospital mortality was significantly higher in STEMI patients than NSTEMI patients (7.7 vs 5.1 %, p < 0.007). Independent correlates of in-hospital mortality were advanced age, low blood pressure, and high Killip classification, statin-treated dyslipidemia and PCI within 24 h were favorable predictors for STEMI. High Killip classification, high heart rate, and hemodialysis were significant predictors of in-hospital mortality, whereas statin-treated dyslipidemia was the only favorable predictor for NSTEMI. In conclusion, patients with MI received PCI frequently (83.5 %) and promptly (door-to-balloon time; 66 min), and had favorable in-hospital prognosis (in-hospital mortality; 7.0 %). In addition to traditional predictors of in-hospital death, statin-treated dyslipidemia was a favorable predictor of in-hospital mortality for STEMI and NSTEMI patients, whereas hemodialysis was the strongest predictor for NSTEMI patients.