Background— The proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes independently of its enzymatic activity the degradation of the low-density lipoprotein (LDL) receptor. PCSK9 gain of function in humans leads to autosomal dominant hypercholesterolemia, whereas the absence of functional PCSK9 results in ≈7-fold lower levels of LDL cholesterol. This suggests that lowering PCSK9 may protect against atherosclerosis. Methods and Results— We investigated the role of PCSK9 in atherosclerosis in C57BL/6 wild-type (WT), apolipoprotein E–deficient, and LDL receptor–deficient mouse models. Circulating cholesterol levels, fast protein liquid chromatography profiles, aortic cholesteryl esters (CE), and plaque sizes were determined. Intima-media thicknesses were measured by ultrasound biomicroscopy. First, mice expressing null (knockout [KO]), normal (WT), or high (transgenic [Tg]) levels of PCSK9 … arabic 12 English 86
Maxime Denis, Ahmed Zaid(1-2012)

Abstract Introduction: Extended-spectrum β-lactamases (ESBLs), AmpC type, carbapenem resistant Enterobacteriaceae (CRE), are important mechanisms of resistance among Enterobacteriaceae. The aim of this study was to investigate the prevalence of ESBL, AmpC and CRE among Enterobacteriaceae isolates recovered from pediatric patients in Tripoli, Libya. Methods: This cross-sectional study was carried out in Tripoli Children Hospital (TCH), a total of 915 Gram negative bacteria isolates were evaluated for susceptibility to a panel of antimicrobials and were analyzed phenotypically for the ESBL, AmpC type and CRE using chromagen media, E-test and combination disc test. Results: The predominant organisms were Escherichia coli (56.8%) and Klebsiella spp. (21.4%). The overall prevalence of ESBL producing Enterobacteriaceae was 24.5% (224/915). Out of 224, Enterobacteriaceae proved ESBL producer, Klebsiella spp. (54%) and E. coli (34.4%) were the leading ESBL producers. ESBL-producers were more often resistant to major classes of antibiotics compared with non-ESBL producers, significantly high resistance rates (P < 0.001) were observed for ceftriaxone, cefepime, and ceftazidime (87.5 - 95.9%) among ESBL producers compared to non-ESBL producers (7.2 - 13.5%). MDR was documented for 50/224 (22.3%) of ESBL producers and was significantly higher (P < 0.0001) among ESBLs compared with non-ESBL producer isolates. Phenotypic detection of AmpC revealed 60/915 (6.6%) isolates as potential AmpC β-lactamase producers, E. coli exhibited a lower level of AmpC (8.3%) compared with Klebsiella spp. (56.6%). The overall prevalence of CRE was 9% (83/915). Carbapenemase-producing organisms in this study were as follows: Klebsiella spp. (44.6%); Acinetobacter spp. (24%); Pseudomonas spp. (9.6%). Conclusion: This study revealed that the prevalence of ESBL, AmpC, CRE and MDR Enterobacteriaceae isolates in Children hospital was within acceptable frequency. arabic 11 English 91
Abdulaziz Zorgani, Abdulla Bashein, (1-2017)

Accumulating evidence indicates the role of endocrine disruptor bisphenol A (BPA) in many pathological conditions. Histone deacetylase (HDAC) inhibition has potential for the treatment of many diseases/abnormalities. Using a mouse BPA exposure model, this study investigated the hepatoprotective effects of the Food and Drug Administration–approved HDAC2 inhibitor valproic acid (VPA) against BPA-induced liver pathology. We randomly divided 30 adult male Swiss albino mice (8 weeks old; N = 6) into five groups: group 1, no treatment (sham control (SC)); group 2, only oral sterile corn oil (vehicle control (VC)); group 3, 4 mg/kg/day of oral BPA (single dose (BPA group)); group 4, 0.4% oral VPA (VPA group); and group 5, oral BPA + VPA (BPA + VPA group). At the age of 10 weeks, the mice were euthanized for biochemical and histological examinations. BPA promoted a significant decrease in the body weight (BW), an increase in the liver weight, and a significant increase in the levels of liver damage markers aspartate aminotransferase and alanine aminotransferase in the BPA group compared to SC, as well as pathological changes in liver tissue. We also found an increase in the rate of apoptosis among hepatocytes. In addition, BPA significantly increased the levels of oxidative stress indices, malondialdehyde, and protein carbonylation but decreased the levels of reduced glutathione (GSH) in the BPA group compared to SC. In contrast, treatment with the HDAC2 inhibitor VPA significantly attenuated liver pathology, oxidative stress, and apoptosis and also enhanced GSH levels in VPA group and BPA + VPA group. The HDAC2 inhibitor VPA protects mice against BPA-induced liver pathology, likely by inhibiting oxidative stress and enhancing the levels of antioxidant-reduced GSH.
Mohamed A. Al-Griw, Zaynab Osama Alshibani, Rabia Omar abdullah Alghazeer, Mohamed Elhensheri, Refaat. M. Tabagh, Areej A. Eskandrani, Wafa S. Alansari, Mahmoud M. Habibulla, Ghalia Shamlan(6-2022)