Clinical characteristics of patients with alcohol dependence comorbid with hypertension among regular drinkers: An internet-based, cross-sectional study in Japan.

While evidence suggests a strong association between alcohol and hypertension, little is known about the profile of patients with alcohol dependence comorbid with hypertension. This study aimed to clarify the clinical characteristics and health problems of this population through a web-based questionnaire survey using a research company's panel of adults in Japan. Of 20 000 regular drinkers, 176 on treatment for hypertension and with alcohol dependence (confirmed and/or an Alcohol Use Disorders Identification Test score ≥15 points) were included.

Long-term safety and efficacy of nalmefene in Japanese patients with alcohol dependence.

Aim: The safety and efficacy of nalmefene in Japanese patients with high or very high World Health Organization drinking risk level of alcohol dependence were assessed in a multicenter, randomized, double-blind, placebo-controlled, phase 3 (lead-in) study. Here, the long-term safety and efficacy of nalmefene in an open-label extension of the lead-in study are presented.

Methods: Patients who completed the 24-week lead-in study were eligible for the extension study, where they were treated with nalmefene 20 mg as needed for 24 weeks.

OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor.

There is an urgent need for new, potent antituberculosis (anti-TB) drugs with novel mechanisms of action that can be included in new regimens to shorten the treatment period for TB. After screening a library of carbostyrils, we optimized 3,4-dihydrocarbostyril derivatives and identified OPC-167832 as having potent antituberculosis activity. The MICs of the compound for ranged from 0.

Delamanid Kills Dormant Mycobacteria and in a Guinea Pig Model of Tuberculosis.

Tuberculosis (TB) treatment is long and requires multiple drugs, likely due to various phenotypes of TB bacilli with variable drug susceptibilities. Drugs with broad activity are urgently needed. This study aimed to evaluate delamanid's activity against growing or dormant bacilli as well as Cultures of BCG Tokyo under aerobic and anaerobic conditions were used to study the activity of delamanid against growing and dormant bacilli, respectively.

Distinct propagation efficiencies of H5N1 influenza virus Thai isolates in newly established murine respiratory region-derived cell clones.

Inbred mice have been widely used for the study of influenza viruses as a mammalian model, while suitable cell lines derived from murine tissue have been limited. Here, we established several immortalized cell clones from respiratory regions of inbred mice (C57BL/6 and BALB/c) by transformation using simian virus 40 large T antigen expression vector. Twenty-five cell clones from C57/BL and BALB/c, designated as MRDC/C and MRDC/B series, respectively, showed different susceptibility to Thai isolates of influenza A virus H5N1.

GPI-anchorless human prion protein is secreted and glycosylated but lacks superoxide dismutase activity.

Prion protein (PrP) is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that is thought to play a role in anti-oxidative stress. It remains controversial whether PrP elicits superoxide dismutase (SOD) activity itself or indirectly by activating cellular SOD. Our previous studies showed that soluble PrP produced by a baculovirus expression system did not exhibit any SOD activity in a marginally glycosylated form.

A monoclonal antibody (1D12) defines novel distribution patterns of prion protein (PrP) as granules in nucleus.

A monoclonal antibody (mAb) panel to bovine prion protein (PrP) was studied by immunoblotting and immunohistochemistry for scrapie and bovine spongiform encephalopathy. A mAb panel recognized both normal (PrP(C)) and abnormal (PrP(Sc)) isoforms of PrP in murine, ovine and bovine brain tissues. Interestingly, an anti-bovine PrP mAb, 1D12, prepared by immunizing PrP gene-knockout mice with a synthetic polypeptides corresponding to codons 153-166 of the bovine PrP gene showed novel patterns of reactivity for prion-uninfected neuronal cells.

Recent developments in prion disease research: diagnostic tools and in vitro cell culture models.

After prion infection, an abnormal isoform of prion protein (PrP(Sc)) converts the cellular isoform of prion protein (PrP(C)) into PrP(Sc). PrP(C)-to-PrP(Sc) conversion leads to PrP(Sc) accumulation and PrP(C) deficiency, contributing etiologically to induction of prion diseases. Presently, most of the diagnostic methods for prion diseases are dependent on PrP(Sc) detection.

Novel single nucleotide polymorphisms in the specific protein 1 binding site of the bovine PRNP promoter in Japanese Black cattle: impairment of its promoter activity.

Susceptibility to transmissible spongiform encephalopathy and different alleles of the prion protein gene (PRNP) of humans and sheep are associated. A tentative association between PRNP promoter polymorphisms and bovine spongiform encephalopathy (BSE) susceptibility has been reported in German cattle, whereas none of the known polymorphisms within the bovine PRNP-coding sequence affect BSE susceptibility. In the present study, novel single nucleotide polymorphisms located in the 5'-flanking region of bovine PRNP affecting its expression were demonstrated in Japanese Black cattle.

Neurotoxic prion protein (PrP) fragment 106-126 requires the N-terminal half of the hydrophobic region of PrP in the PrP-deficient neuronal cell line.

The cytotoxicity of aged PrP(106-126) was examined using an immortalized prion protein (PrP) gene-deficient neuronal cell line. The N-terminal half of the hydrophobic region (HR) but not the octapeptide repeat (OR) of PrP was required for aged PrP(106-126) neurotoxicity, suggesting that neurotoxic signals of aged PrP(106-126) are mediated by this region.

Cell-autonomous PrP-Doppel interaction regulates apoptosis in PrP gene-deficient neuronal cells.

The Prnd-encoded prion protein (PrP)-like protein, Doppel (Dpl), is a homologue of Prnp-encoded PrP, and is N-glycosylated protein with glycosylphosphatidylinositol anchor like PrP. Recently, ectopic expressions of Prnp/Prnd chimeric mRNAs have been identified as the cause of late-onset ataxia observed in several lines of Prnp-knockout mice such as ZrchII, Ngsk, Rcm0, and Rikn mice. However, it remains unclear whether the toxic effect of Dpl expression is a cell-autonomous mechanism but rather reflect a systemic process of heterogeneous cell population in the brain.

Cellular prion protein regulates intracellular hydrogen peroxide level and prevents copper-induced apoptosis.

The function of cellular prion protein (PrPC), which is a copper binding protein, remains unclear. To elucidate the mechanisms in which PrPC is involved in neuroprotection, we compared death signals in prion protein gene-deficient (Prnp-/-) primary cerebellar granular neurons (CGNs) to those with wild-type (WT) CGNs. When copper was exposed to these CGNs, ZrchI, and Rikn Prnp-/- CGNs were more sensitized and underwent apoptotic cell death more readily than WT CGNs.