The inhibition of CYP1A2, CYP2C9, and CYP2D6 by pterostilbene in human liver microsomes.

This study used human liver microsomes to assess pterostilbene's effect on the metabolic activity of cytochrome P450 (CYP) 1A2, CYP2C9, and CYP2D6. The metabolism of their substrates (phenacetin, tolbutamide, and dextromethorphan) was assayed by quantifying their relevant metabolites by HPLC. The IC50 value was used to express the strength of inhibition, and the value of a volume per dose index (VDI) was used to indicate the metabolic ability of the enzyme. In this study, pterostilbene inhibited CYP1A2, CYP2C9, and CYP2D6's metabolic activities in vitro. CYP2C9's activity was most significantly inhibited by pterostilbene; its IC50 value was 0.12±0.04 µM. The IC50 value of CYP1A2 and CYP2D6 was 56.3±10.4 µM and 62.33±11.4 µM, respectively. The finding that suggests that pterostilbene has the potential to interact with CYP2C9 substrates in vivo. These results warrant clinical studies to assess the in vivo significance of these interactions.

Healthcare workers' knowledge and attitudes towards COVID-19 in Saudi Arabia.

OBJECTIVE: The world is facing a devastating challenge in the COVID-19 (coronavirus disease 19) outbreak.  Healthcare workers (HCWs) provide the first line of defense against any disease outbreak. Thus, the present study is designed to assess HCWs' attitudes towards, knowledge of, and awareness of COVID-19. MATERIALS AND METHODS: A cross-sectional observational study was conducted using an online survey on social media; the participants were 597 adults. The study was conducted from March to April 2020. The questionnaire was randomly administered on Arabic-language social media applications; the 26-item survey assessed knowledge levels, attitudes, and practices. RESULTS: The analysis includes 597 complete responses from HCWs; participants included physicians, nurses, medical students, and pharmacists. Most participants were females aged 18 to 25 years. Most participants agreed that the virus can spread via direct and indirect contact. Most participants indicated that they wash their hands; avoid touching their eyes, nose, or mouth; and avoid crowded places to protect themselves against infection. Most indicated that a bat was the original source of the virus. Most participating HCWs indicated that the symptoms of COVID-19 include fever, cough, and shortness of breath. Most of the participants also indicated that there is no specific treatment for patients infected with COVID-19. CONCLUSIONS: The findings of this work can support the design of effective measures to prevent and control COVID-19 infections during the pandemic. The results also highlight where improvement is needed to HCWs' knowledge of and attitudes towards COVID-19; the findings also highlight the best healthcare practices regarding this illness.

Current Status and Future Direction of Hepatic Radioembolisation.

Radioembolisation is a locoregional treatment modality for hepatic malignancies. It consists of several stages that are vital to its success, which include a pre-treatment angiographic simulation followed by nuclear medicine imaging, treatment activity choice, treatment procedure and post-treatment imaging. All these stages have seen much advancement over the past decade. Here we aim to provide an overview of the practice of radioembolisation, discuss the limitations of currently applied methods and explore promising developments.

Prevalence, knowledge and attitude of prohibited substances use (doping) among Saudi sport players.

BACKGROUND: To estimate the lifetime prevalence and address the attitudes and knowledge of using prohibited substances (doping) among sport players in Saudi Arabia. METHODS: A cross-sectional survey carried out using systematic random sampling technique among Saudi players of variable sports attending the sport clubs, stadiums, and sport fields (70 sport clubs, 22 types of sports belong to 22 Saudi sport federations were visted in 18 cities from all regions of Saudi Arabia). RESULTS: A total of 1142 male sport players were interviewed with main age of 24. The prevalence of using prohibited substances (doping) was 4.3 %. The main reason for using prohibited substances was to improve performance (69 %). The prevalence of using food supplements (not prohibited) was 38.4 %. Among the players, 30 % of them believe that such behavior is against the spirit of sport while 70 % of the players are aware of punishment against doping. 65 % of players admitted that they received advice on prohibited substances. Higher rate of using prohibited substances (doping) among Saudi players was associated with low education, age below 20 years, previous use of food supplements and lack of punishment awareness. CONCLUSION: Using prohibited substances (doping) among Saudi sport players is common. Players believe that such use is against the spirit of the sport and they are aware about its punishment, despite this, they are still using prohibited substances.

Optimizing the clinical pharmacology of tuberculosis medications.

Tuberculosis (TB) treatment has changed little in the past 40 years. The current standard therapy requires four drugs for 2 months followed by two drugs for 4 months. This "short-course" regimen is not based on optimized pharmacokinetic and pharmacodynamic properties, but empiric evidence. A review of existing data suggests that pharmacokinetic variability with isoniazid and rifampin is greater than previously thought, and that efficacy is not as good as traditionally reported. Adding new drugs to the current regimen will be costly and time-consuming. Maximizing the efficacy of the current medications is a less expensive and more feasible option. This article reviews the current potential of the first-line TB drugs (rifamycins, isoniazid, pyrazinamide, and ethambutol) as well as the fluoroquinolones to introduce a true short-course TB regimen.

BCL11A enhancer haplotypes and fetal hemoglobin in sickle cell anemia.

BACKGROUND: Fetal hemoglobin (HbF) levels in sickle cell anemia patients vary. We genotyped polymorphisms in the erythroid-specific enhancer of BCL11A to see if they might account for the very high HbF associated with the Arab-Indian (AI) haplotype and Benin haplotype of sickle cell anemia. METHODS AND RESULTS: Six BCL112A enhancer SNPs and their haplotypes were studied in Saudi Arabs from the Eastern Province and Indian patients with AI haplotype (HbF ~20%), African Americans (HbF ~7%), and Saudi Arabs from the Southwestern Province (HbF ~12%). Four SNPs (rs1427407, rs6706648, rs6738440, and rs7606173) and their haplotypes were consistently associated with HbF levels. The distributions of haplotypes differ in the 3 cohorts but not their genetic effects: the haplotype TCAG was associated with the lowest HbF level and the haplotype GTAC was associated with the highest HbF level and differences in HbF levels between carriers of these haplotypes in all cohorts were approximately 6%. CONCLUSIONS: Common HbF BCL11A enhancer haplotypes in patients with African origin and AI sickle cell anemia have similar effects on HbF but they do not explain their differences in HbF.

Population pharmacokinetics of rifampin in the treatment of Mycobacterium tuberculosis in Asian elephants.

The objective of this study was to develop a population pharmacokinetic model for rifampin in elephants. Rifampin concentration data from three sources were pooled to provide a total of 233 oral concentrations from 37 Asian elephants. The population pharmacokinetic models were created using Monolix (version 4.2). Simulations were conducted using ModelRisk. We examined the influence of age, food, sex, and weight as model covariates. We further optimized the dosing of rifampin based upon simulations using the population pharmacokinetic model. Rifampin pharmacokinetics were best described by a one-compartment open model including first-order absorption with a lag time and first-order elimination. Body weight was a significant covariate for volume of distribution, and food intake was a significant covariate for lag time. The median Cmax of 6.07 µg/mL was below the target range of 8-24 µg/mL. Monte Carlo simulations predicted the highest treatable MIC of 0.25 µg/mL with the current initial dosing recommendation of 10 mg/kg, based upon a previously published target AUC0-24/MIC > 271 (fAUC > 41). Simulations from the population model indicate that the current dose of 10 mg/kg may be adequate for MICs up to 0.25 µg/mL. While the targeted AUC/MIC may be adequate for most MICs, the median Cmax for all elephants is below the human and elephant targeted ranges.

High frequency of carbapenem-resistant Acinetobacter baumannii in patients with diabetes mellitus in Saudi Arabia.

Carbapenem-resistant Acinetobacter baumannii is becoming increasingly prevalent in patients with diabetes mellitus in the Middle East. We examined the relationship of these bacteria and their resistance mechanisms to the diabetic disease status of patients in Saudi Arabia. Susceptibilities of 271 isolates to carbapenems, tigecycline and colistin were determined, followed by detection of carbapenemase genes. A blaVIM gene was detected in ~95 % of isolates; blaOXA-23 and blaOXA-40 genes were also prevalent. Diabetic patients were significantly more likely to carry carbapenem-resistant isolates. Carbapenem-resistant A. baumannii is a serious problem in diabetic patients, and molecular detection of resistance mechanisms in these isolates is required.

GVHD after unrelated cord blood transplant in children: characteristics, severity, risk factors and influence on outcome.

We reviewed our experience in 79 children who had unrelated cord blood transplant (UCBT) between 1996 and 2007 with a major focus on GVHD, comparing both traditional and National Institute of Health (NIH) criteria. The cumulative incidence (CI) of acute GVHD (aGVHD, by day +100) was 0.42 for grade II-IV and 0.22 for grade III-IV. The CI of all aGVHD (NIH, that is, no time limit) at 1 year was 0.45 for grade II-IV and 0.32 for grade III-IV. Infused CD34 cell dose (>1 × 10(5)/kg), pretransplant bacterial infection and nonmalignant disorders were risk factors for grade II-IV aGVHD on univariate analysis. Infused CD34 cell dose remained significant on multivariate analysis. At 1 year, the CI of chronic GVHD (cGVHD) using the Seattle criteria was 0.27, whereas that for cGVHD (NIH) was 0.08. By NIH criteria, the classic form of cGVHD was uncommon (5%) after UCBT. Instead, the acute (71%) and overlap (24%) GVHD variants predominated. Grade II-IV aGVHD was a significant risk factor for cGVHD by both Seattle and NIH criteria. We conclude that GVHD after day +100 after UCBT typically carries features of aGVHD. Moreover, and in marked contrast to adult unrelated donor hematopoietic stem cell transplantation, the GVHD observed in this series did not adversely affect survival.

Relationship between oxidative stress, ferritin and insulin resistance in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by hemolytic anemia. The oxidative phenomena play a significant role in its pathophysiology. Blood transfusions are a therapeutic mainstay in SCD and repeated transfusions can result in iron overload. There is little direct information available to confirm the correlation between the oxidative stress, iron overload and insulin resistance in SCD patients. OBJECTIVE: To investigate the relationship between iron overload, the disorders of antioxidants and insulin levels in blood of SCD patients and their matched controls. METHODS: The antioxidant activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as the malondialdehyde (MDA, the membrane lipid peroxidation products) and carbonyl contents (the oxidative products of proteins) were estimated spectrophotometrically in erythrocytes of patients and control subjects of matched sex and ages. In addition, fasting blood glucose (FBG), ferritin and insulin levels were estimated in the sera of the same subjects. RESULTS: The mean activity values of SOD, CAT and GSH-Px were significantly decreased, whereas the average values of MDA and carbonyl contents were significantly increased in erythrocytes of SCD patients in comparison to the corresponding values of the control subjects. The average levels of FBS, ferritin, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly elevated in the sera of SCD patients as compared to the controls. In addition, both serum ferritin, and oxidative products (expressed as MDA and carbonyl levels) were significantly correlated with blood glucose, insulin level, and HOMA-IR. CONCLUSION: These findings may explain the role of elevated ferritin and oxidative products (i.e. MDA & carbonyl contents) in the development of insulin resistance and high glucose levels in SCD patients.

Acinetobacter baumannii: emergence of four strains with novel bla(OXA-51-like) genes in patients with diabetes mellitus.

UNLABELLED: Diabetic patients are 10 times more likely to develop Acinetobacter baumannii infections than the rest of the population. Carbapenems are considered one of the very few antibiotics left to treat infections caused by this organism. the aim of this work was to characterise A. baumannii strains isolated from diabetic patients and to investigate whether there is a relationship between certain strains and low-level-carbapenem resistance. METHODS: Clinical samples were collected from diabetic patients in hospitals throughout Saudi Arabia from December 2006 to April 2007. API 20 Ne, polymorphisms in the 16S-23S-rRNA intergenic region and the presence of a bla( OXA-51-like )gene were all used for identification. Susceptibility to antimicrobials was determined using agar dilution and disk diffusion methods. pulsed-field gel electrophoresis (pfGe) coupled with sequence analysis of the bla(OXA-51-like )genes were used for strain characterization. Polymerase chain reaction (pCR) and multiplex pCR were used to screen for the presence and location of ISAba1 elements and bla(OXA-23-like), bla(OXA-40-like), and bla(OXA-58-like )genes respectively. RESULTS: Twenty isolates were identified as A. baumannii and were all highly resistant to 38% of the antibiotics tested and the majority of isolates were also resistant to 50% of the remaining antibiotics. four strains had low-level meropenem resistance (MIC 4-8 mg/l). All isolates were sensitive to imipenem and colistin. Nine strains possessed four novel bla( OXA-51-like )genes encoding beta-lactamases designated OXA-90, OXA-130, OXA-131 and OXA-132, and four strains contained bla(OXA-131 )with ISAba1 upstream of the gene structure. PFGE showed five separate clusters of OXA-51-like enzymes and the dissemination of strains carrying the four novel enzymes was clonal. this study showed that new strains of A. baumannii characterised by their new bla(OXA-51-like )gene have emerged. No genes encoding OXA-23-like, OXA-40-like, or OXA-58-like beta-lactamases were found. Surveillance of A. baumannii harbouring the bla( OXA-131-like )gene may be an essential step in monitoring their carbapenem resistance phenotype and may assist in preventing their spread in diabetics.