Criteria for diagnosis of familial hypercholesterolemia: a comprehensive analysis of the different guidelines, appraising their suitability in the Omani Arab population

Subjects with Familial hypercholesterolemia are at increased risk for cardiac events such as premature myocardial infarction and early death from coronary heart disease, especially in patients with severe forms of the disease if left unattended. Therefore, there is an ardent need for the early diagnosis followed by aggressive therapeutic intervention and lifestyle modification. Three groups have developed clinical diagnostic tools for Familial hypercholesterolemia: the US MedPed Program, the Simon Broome Register Group in the United Kingdom, and the Dutch Lipid Clinic Network. In this article, the individual criteria are reviewed with particular emphasis on their advantage[s] and disadvantage[s], and in turn assess their suitability in diagnosing Familial hypercholesterolemia in the Omani Arab population. A brief insight into the process of "Cascade Screening" is also provided, this is a procedure that we are in the process of establishing in Oman.

Mutation in the PCSK9 gene in Omani Arab subjects with autosomal dominant hypercholesterolemia and its effect on PCSK9 protein structure

Proprotein convertase subtilisin/kexin type [PCSK9] is a crucial protein in LDL cholesterol [LDL-C] metabolism by virtue of its pivotal role in the degradation of the LDL receptor. Mutations in the PCSK9 gene have previously been found to segregate with autosomal dominant familial hypercholesterolemia [ADFH]. In this study, DNA sequencing of the 12 exons of the PCSK9 gene has been performed for two patients with a clinical diagnosis of familial hypercholesterolemia where mutation in the LDL-receptor gene hasn't been excluded. One missense mutation was detected in the exon 9 PCSK9 gene in the two ADFH patients. The patients were found to be heterozygote for Ile474Val [SNP rs562556] Using an array of in silico tools, we have investigated the effect of the above mutation on different structural levels of the PCSK9 protein Although, the mutation has already been reported in the literature for other populations, to the best of our knowledge this is the first report of a mutation in the PCSK9 gene from the Arab population, including the Omani population

Saphenous vein graft vs. radial artery graft searching for the best second coronary artery bypass graft

Coronary artery bypass grafting [CABG] was first used in the late 1960s. This revolutionary procedure created hope among ischemic heart disease patients. Multiple conduits are used and the golden standard is the left internal mammary artery to the left anterior descending artery. Although all approaches were advocated by doctors, the use of saphenous vein grafts became the leading approach used by the majority of cardiac surgeons in the 1970s. The radial artery graft was introduced at the same time but was not as prevalent due to complications. It was reintroduced into clinical practice in 1989. The procedure was not well received initially but it has since shown superiority in patency as well as long-term survival after CABG. This review provides a summary of characteristics, technical features and patency rates of the radial artery graft in comparison with venous conduits. Current studies and research into radial artery grafts and saphenous vein grafts for CABG are explored. However, more studies are required to verify the various findings of the positive effects of coronary artery bypass grafting with the help of radial arteries on mortality and long-lasting patency.

In silico design of novel anticoagulant peptides targeting blood coagulation factor VIIa

The coagulation cascade initiated during vascular injury prevents bleeding. Unwanted clot formation is however detrimental and requires the use of anticoagulants for prophylaxis and treatment. Anticoagulants targeting a specific step or an enzyme in the clotting process are most preferred as they minimise disadvantageous side-effects. A principal step in the discovery of novel anticoagulants encompasses the in silico design of potential leads. This study depicts the in silico design of peptide anticoagulants targeting coagulation factor VIIa. Applying the proline bracket rule and using various bioinformatics tools: the basic alignment search tool [BLAST] of National Center for Biotechnology Information; the T-coffee module provided by European Molecular Biology Laboratory-European Bioinformatics Institute, and several modules available on the ExPASy server, we designed five bivalent chimeric anticoagulants targeting factor VIIa, using factor VIIa inhibitors - hemextin A from Hemachatus haemachatus [African Ringhals cobra] venom and factor VIIa exosite-inhibitor peptide as templates. Six peptides were derived from hemextin A, which were concomitantly fused with factor VIIa exosite-inhibitor peptide intermediated by a polyalanine spacer, and analysed for structural stability using the SWISS-MODEL software developed at the Swiss Institute of Bioinformatics and WebLab ViewerPro [Version 4.2]. Twelve chimeric peptides were obtained; only five exhibited stable structures in silico. The five peptides obtained are probable anticoagulant leads that should be further evaluated using suitable in vitro and in vivo assays. Further, this study shows how simple web-based modules can be used for the rational design of probable leads targeting specific physiological molecular targets