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)

The detection of somatic mutations in tumours is essential for the understanding of cancer development and targeting therapy. The screening for BRAF V600E mutation is employed in clinical practice in Libya for its prognostic and potentially predictive role in patients with metastatic colorectal carcinoma (mCRC). Using of BRAF mutant DNA and wild type DNA targets, we found that the sensitivity of allelic discrimination-Real Time PCR was applicable. The Real Time PCR assay displayed increased analytical sensitivity in detecting the BRAF V600E mutation. The association of BRAF mutations with clinical and pathological features was assessed using Real Time PCR assay. Qiagen Real Time PCR Platform was utilised using a set of primers. forward 5-GAC. CTC. ACA. GTA. AAA. ATA. GGT. G 3, reverse 5-TCC. AGA. CAA. CTG. TTC. AAA. CTG. A. 3. Our study indicates that Real Time PCR-based assays is convenient to detect the BRAF V600E mutation in CRC and that BRAF mutations screening should not be restricted to selected patients on the basis of the clinicalpathological characteristics. arabic 9 English 63
Abdul M Gbaj, Abdulla Bashein(1-2018)

Background: Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that catalyses the S-methylation of 6-mercaptopurine and azathioprine. Low activity phenotypes are correlated with polymorphism in the TPMT gene. Patients with low or undetectable TMPT activity could develop severe myelosuppression when they are treated with standard doses of thiopurine drugs. Since ethnic differences in the TPMT gene polymorphism have been demonstrated worldwide, assessing it in the Libyan population is worthwhile. Methods: We investigated TPMT gene polymorphism in a total of 246 Libyan healthy adult blood donors from three different Libyan regions (Tripoli, Yefren, and Tawargha) and 50 children with acute lymphoblastic leukaemia (ALL). We used polymerase chain reaction restriction length polymorphism (PCR-RFLP) and allele-specific PCR-based assays to analyse the TPMT gene for the variants* 2 c. 238 G> C,* 3A (c. 460 G> A and c. 719 A> G),* 3B (c. 460 G> A), and* 3C (c. 719 A> G). Results: Our results show that the TPMT variants associated with low enzymatic activity were detected in 3.25%(8 in 246) of adult Libyan individuals and the frequency of total mutant alleles was 1.63%. Heterozygous genotypes were TPMT* 3A in three subjects (0.61%) and TPMT* 3C in five subjects (1.02%). No TPMT* 2 and TPMT* 3B allelic variants and no homozygous or compound heterozygous mutant alleles were detected. The normal allele (wild-type) was found in 98.4% of the adult individuals studied. No mutant alleles were detected among the 50 children who had ALL. arabic 10 English 74
Hamza Ben Zeglam, Abdulla Bashein, (1-2015)