Hepatotoxicity and Associated Risk Factors in Hiv-Infected Patients Receiving Antiretroviral Therapy at Felege Hiwot Referral Hospital, Bahirdar, Ethiopia

Background: In Human Immunodeficiency Virus (HIV) infected patients on antiretroviral treatment (ART), hepatotoxicity is life threatening. Its outcome may lead to liver failure and death. This study was conducted to determine the rate and determinants of elevated alanine amino transferase (ALT) (referred as >40IU/L for both males and females).Methods: A cross sectional study was conducted on HIV infected individuals who are on ART and suspected of drug resistance at Felege Hiwot Referral Hospital, Bahir Dar from July to December 2012. Venous bloods were collected from each patient and processed parallely to determine ALT, number of HIV RNAs, CD4 and CD8 T cells count, anti hepatitis C virus (HCV) and hepatitis B surface antigen.Results: Out of 269 HIV infected patients receiving ART, 32% were confirmed of grades 1-4 levels of elevated ALT. The rate of severe hepatotoxicity (grade 3 and 4) was 1.84%. Patients with increased CD8 T cell counts (P=0.011; AOR=1.82; CI: 1.12 - 2.54), alcohol over use (P=0.014; AOR = 1.23; CI: 1.36- 3.29) and detectable HIV-1 RNA copies (P=0.015; AOR=2.07; CI: 1.15-3.74) independently predicts the elevation of ALT.Conclusions: In HIV infected patients on ART, extreme elevations of ALT were infrequent but minor elevations were common so that patient-linked variables such as use of alcohol intake must be taken in to account for better clinical management of ART patients. The role of active HCV co-infection on the treatment outcome of ART should be further studied.Key words: ALT, HIV, ART, Bahir Dar, Ethiopi

Mechanical Property of Plastic Lumber Produced from Recycled High Density Polyethylene (HDPE)

Recycling is a strategy to combat environmental pollution due to plastic wastes. Of the many plastic wastes, researchers confirmed the possibility to produce plastic lumber from used HDPE plastics. The aim of this study is to experimentally determine the mechanical property of the plastic lumber produced from pure HDPE and its composite with wood to proof usability and applicability for different purpose. The experiment considered different conditions. Pure plastic lumber and wood plastic composite lumber is initially produced and examined under room temperature and below room temperature. Under each condition, bending, tensile and impact strength were examined. For each test eight specimens were prepared based on international standards and the experiments were conducted using standard testing machines. The result shows that pure plastic lumber has demonstrated superior load carrying capability, tensile load resistance capability and impact load resistance at room temperature. Moreover, the pure plastic lumber has an elastic nature and the wood composite has a brittle nature. In both cases the mechanical property of the plastic lumber permits to use for different applications. This has been also tested and resulted in similar phenomena at 20C below room temperature

Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs

Cholinesterase inhibitors, the current frontline symptomatic treatment for Alzheimer’s disease (AD), are associated with low efficacy and adverse effects. M1 muscarinic acetylcholine receptors (M1 mAChRs) represent a potential alternate therapeutic target; however, drug discovery programs focused on this G protein-coupled receptor (GPCR) have failed, largely due to cholinergic adverse responses. Employing novel chemogenetic and phosphorylation-deficient, G protein-biased, mouse models, paired with a toolbox of probe molecules, we establish previously unappreciated pharmacologically targetable M1 mAChR neurological processes, including anxiety-like behaviors and hyper-locomotion. By mapping the upstream signaling pathways regulating these responses, we determine the importance of receptor phosphorylation-dependent signaling in driving clinically relevant outcomes and in controlling adverse effects including ‘epileptic-like’ seizures. We conclude that M1 mAChR ligands that promote receptor phosphorylation-dependent signaling would protect against cholinergic adverse effects in addition to driving beneficial responses such as learning and memory and anxiolytic behavior relevant for the treatment of AD