Protein structural insights into a rare PCSK9 gain-of-function variant (R496W) causing familial hypercholesterolemia in a Saudi family: whole exome sequencing and computational analysis.

Familial hypercholesterolemia (FH) is a globally underdiagnosed genetic condition associated with premature cardiovascular death. The genetic etiology data on Arab FH patients is scarce. Therefore, this study aimed to identify the genetic basis of FH in a Saudi family using whole exome sequencing (WES) and multidimensional bioinformatic analysis.

Major obstacles to doxorubicin therapy: Cardiotoxicity and drug resistance.

Background: Doxorubicin is one of the most commonly prescribed and time-tested anticancer drugs. Although being considered as a first line drug in different types of cancers, the two main obstacles to doxorubicin therapy are drug-induced cardiotoxicity and drug resistance.

Method: The study utilizes systemic reviews on publications of previous studies obtained from scholarly journal databases including PubMed, Medline, Ebsco Host, Google Scholar, and Cochrane.

Dilemmas of the causality assessment tools in the diagnosis of adverse drug reactions.

Importance: Basic essence of Pharmacovigilance is prevention of ADRs and its precise diagnosis is crucially a primary step, which still remains a challenge among clinicians.

Objective: This study is undertaken with the objective to scrutinize and offer a notion of commonly used as well as recently developed methods of causality assessment tools for the diagnosis of adverse drug reactions and discuss their pros and cons.

Evidence Review: Overall 49 studies were recognized for all assessment methods with five major decisive factors of causality evaluation, all the information regarding reasons allocating causality, the advantages and limitations of the appraisal methods were extracted and scrutinized.

Serum Interleukin-33 level in Saudi children with inflammatory bowel disease.

Interleukin-33 (IL-33) is a cytokine that belongs to the interleukin-1 family and has been shown to be associated with mucosal inflammation. The aim of this study was to determine the serum level of IL-33 in children with ulcerative colitis (UC) and Crohn's disease (CD) and to correlate the level with the disease progression. In this cross sectional prospective study, we enrolled 50 children with IBD from KAUH, Jeddah, Saudi Arabia and 34 healthy control subjects between June 2012 and December 2012.

Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients.

Celiac disease (CD), a gluten intolerance disorder, was implicated to have 57 genetic susceptibility loci for Europeans but not for culturally and geographically distinct ethnic populations like Saudi Arabian CD patients. Therefore, we genotyped Saudi CD patients and healthy controls for three polymorphisms, that is, Phe196Ser in IRAK1, Trp262Arg in SH2B3, and Met518Thr in MMEL1 genes. Single locus analysis identified that carriers of the 518 Thr/Thr (MMEL1) genotype conferred a 1.

Detection of adverse drug reactions by medication antidote signals and comparison of their sensitivity with common methods of ADR detection.

Objective: To determine the PPVs of selected ten medication antidote signals in recognizing potential ADRs and comparison of their sensitivity with manual chart analysis, and voluntary reporting recognizing the same ADRs.

Method: The inpatient EMR database of internal medicine department was utilized for a period of one year, adult patients prescribed at least one of the ten signals, were included in the study, recipient patients of antidote signals were assessed for the occurrence of an ADR by Naranjo's tool of ADR evaluation. PPVs of each antidote signal were verified.

The possible antianginal effect of allopurinol in vasopressin-induced ischemic model in rats.

The anti-anginal effects of allopurinol were assessed in experimental model rats of angina and their effects were evaluated with amlodipine. In the vasopressin-induced angina model, oral administration of allopurinol in dose of 10 mg/kg revealed remarkably analogous effects in comparison with amlodipine such as dose-dependent suppression of vasopressin-triggered time, duration and severity of ST depression. In addition, allopurinol produced dose dependent suppression of plasma Malondialdehyde (MDA) level, systolic blood pressure, cardiac contractility and cardiac oxygen consumption; while in contrast, amlodipine minimally suppressed the elevation of plasma MDA level.

Perceptions and knowledge regarding antimicrobial stewardship among clinicians in Jeddah, Saudi Arabia.

Objectives: To understand the perceptions, attitude, and prescribing practices of clinicians regarding antimicrobial resistance (AMR).

Methods: A multidisciplinary cross-sectional study comprising 447 clinicians of university, public, and private hospitals of Jeddah, Saudi Arabia was carried out from August to October 2014 using a self-administered questionnaire.

Results: Interestingly, 33% of the general physicians yielded to patient/parent's demand for the choice of antimicrobials (AMs) as compared with only 13.

Modulatory role of resveratrol on cytotoxic activity of cisplatin, sensitization and modification of cisplatin resistance in colorectal cancer cells.

Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Cisplatin (CIS) is one of the most active cytotoxic agents in current use and it has proven efficacy against various human malignancies. However, its clinical usefulness has been restricted by detrimental side effects, including nephrotoxicity and myelosuppression.

Amelioration of doxorubicin‑induced cardiotoxicity by resveratrol.

Doxorubicin (DOX), is a highly active anticancer agent, but its clinical use is limited by its severe cardiotoxic side‑effects associated with increased oxidative stress and apoptosis. Resveratrol (RSVL) is a naturally occurring polyphenolic compound (trans-3,5,4'-trihydroxystilbene) found primarily in root extracts of the oriental plant Polygonum cuspidatum and of numerous additional plant species. It has recently been shown that RSVL has a number of beneficial effects in different biological systems, which include anti-oxidant, antineoplastic, anticarcinogenic, cardioprotective and antiviral effects.

Appraisal of antimicrobial prescribing practices of governmental and non-governmental dentists for hospitals in the western region of Saudi Arabia.

Objective: To scrutinize the knowledge, attitude, and antimicrobial practices in Saudi Arabian Dentistry.

Methods: In this cross-sectional survey of dentists, a self-administered questionnaire comprising of 61 questions was dispersed to the participants randomly, which included their professional profile, awareness of the current scope of antimicrobial resistance, prescribing practice, frequency of antimicrobial prescription, and sources of continuing education of antimicrobials. The study took place in the Faculty of Dentistry, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia between February and April 2013.

Structural and functional characterization of pathogenic non- synonymous genetic mutations of human insulin-degrading enzyme by in silico methods.

Insulin-degrading enzyme (IDE) is a key protease involved in degrading insulin and amyloid peptides in human body. Several non-synonymous genetic mutations of IDE gene have been recently associated with susceptibility to both diabetes and Alzheimer's diseases. However, the consequence of these mutations on the structure of IDE protein and its substrate binding characteristics is not well elucidated.

Adverse drug reactions in hospitalized pediatric patients of Saudi Arabian University Hospital and impact of pharmacovigilance in reporting ADR.

Objectives: Children are more vulnerable to ADRs, and this susceptibility is compounded due to hospitalization. There is a lack of local data regarding the potential risk of ADRs in hospitalized pediatric patients. Therefore, this study is designed to identify the frequent nature, severity of adverse drug reactions, drugs implicated and factors influencing ADRs.

Chemosensetizing and cardioprotective effects of resveratrol in doxorubicin- treated animals.

Background: Doxorubicin (DOX), an anthracycline antibiotic is one of the most effective anticancer drug used in the treatment of variety of cancers .Its use is limited by its cardiotoxicity. The present study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of mammary carcinoma (Ehrlich ascites carcinoma) to the action of DOX and at the same time its protective effect against DOX-induced cardiotoxicity in rats.

Modulation of doxorubicin cytotoxicity by resveratrol in a human breast cancer cell line.

Background: Breast cancer is the most common cancer in the Arab world and it ranked first among Saudi females. Doxorubicin (DOX), an anthracycline antibiotic is one of the most effective anticancer agents used to treat breast cancer. chronic cardiotoxicity is a major limiting factor of the use of doxorubicin.

Impact of pharmacovigilance on adverse drug reactions reporting in hospitalized internal medicine patients at Saudi Arabian teaching hospital.

Objectives: To determine the incidence, diversity of adverse drug reactions (ADRs), and impact of pharmacovigilance on reporting it.

Methods: This prospective and retrospective study was carried out in the Department of Medicine, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia between January to December 2011 in 600 patients of ADR. Data regarding age and gender distribution of the patients, incidence rate, drugs, body systems/organs involved in ADR, time of occurrence of adverse drug reactions, total number of drugs administered, and impact of pharmacovigilance on finding the incidence rate of ADR were recorded.