Objective: High prevalence of hypovitaminosis D has been reported to be common in different regions of the Middle East. The objective of the present study was to examine the predictors of vitamin D deficiency and insufficiency in Bahrainis.Design: A cross-sectional study.Setting: Blood transfusion volunteers at a blood bank.Subjects: Serum levels of total 25-hydroxyvitamin D, bone markers and other parameters such age, sex, season and clothing style in the 500 healthy Bahrainis were investigated.Results: In the entire cohort the prevalence of vitamin D deficiency was 49·4 % and the relative risk of vitamin D deficiency increased significantly by 1·1, 1·2, 1·5, 1·7 and 1·2 fold with younger age group (P = 0·03), hyperparathyroidism (P = 0·01), low serum Ca (P < 0·001), warm and hot months of the year (P < 0·0001) and female sex (P = 0·002), respectively. In females the prevalence of vitamin D deficiency was 67·6 % and the relative risk of vitamin D deficiency increased significantly by 1·1, 1·2, 1·2, 1·2 and 1·4 fold with younger age group (P = 0·04), hyperparathyroidism (P = 0·03), low serum Ca (P = 0·001), warm and hot months of the year (P = 0·001) and conservative clothing style (P = 0·04), respectively. In contrast, in males the prevalence of vitamin D deficiency was 31·2 % and the relative risk of vitamin D deficiency was increased by 1·6 fold in warm and hot months of the year (P < 0·0001).Conclusions: High prevalence of low circulating levels of vitamin D and the relative risk factors associated with vitamin D deficiency and insufficiency observed in the present study suggest an urgent need for public health interventions including vitamin D food fortification in Bahrain.

Background: Adult patients with sickle-cell disease (SCD) often have multiple bone compactions causing tissue hypoxia and osteonecrosis. The impact on bone abnormalities lesion detected by bone mass density is not well defined. Aim: The study is a cross sectional, perspective was designed to assess the prevalence of abnormal BMD in adult Bahraini patients with SCD and to assess the predictive risk of different metabolic variables such as serum level of vitamin D3, testosterone, and parathyroid hormone in addition to lactate dehydrogenase (LDH), hemoglobin (Hb), and reticulocyte count for the development of abnormal bone density on dual X-ray absorptiometry (DXA) scan. Method: The study was conducted over the period of12 months from first of January 2012 to end of December 2012. All patients were evaluated clinically for severity of SCD and abnormal bone mass density (BMD) using DXA scan. Blood samples were withdrawn for measuring the serum level of vitamin D3, testosterone, and parathyroid hormone in addition to Hb, LDH, and reticulocyte count. Multiple logistic regression analysis was used to assess risk prediction of different variables for the development of abnormal BMD on DXA with T-score ≤–2.5 standard deviation (SD). Results: The study included Bahraini patients with SCD ( n = 55, age 29.24 ± 9.47 years, male 60% and female 40%) compared with an age-matched healthy control group ( n = 55, age 28.82 ± 8.64 years, with 62% male and 38% female). Of the 55 patients with SCD compared with the control group, there were 33 (58%) patients with low BMD and 2 (3%) in the control. Among the 33 patients with SCD and with low BMD, there were 20 (36%) with osteoporosis ( T-score of ≤–2.5 SD) and 13 (24%) with osteopenia ( T-score of <–1 to −2.5 SD). The most affected site of low BMD was lumbar spine (55%), followed by the radius (30%) and neck of the femur (15%). SCD patients with osteoporosis compared with the healthy subjects had significantly lower body surface area (BSA, m²) of 1.4 ± 0.3 vs. 1.63 ± 0.5 BMI, low level of vitamin D3 of 21.11 ± 6.95 ng/mL vs. 46.2 ± 15.19 ( P < 0.001), lower testosterone level of 1.34 ± 0.54 vs. 2.18 ± 0.56 ng/mL ( P < 0.001), higher reticulocyte count ( P < 0.001), and higher LDH level ( P < 0.001). The low serum level of vitamin D3 (<20 ng/mL) and low testosterone of <0.9 ng/mL had risk prediction (odds ratio) of 1.14 and 1.2, respectively, for abnormal BMD in SCD. In the risk prediction of other variables of parathormone (PTH), LDH, and reticulocyte, were not significant. Conclusion: The prevalence of abnormal bone mass density (BMD) is high (60%) in Bahraini patients with SCD. There is significant low serum level of vitamin D3 and low testosterone hormone in those with very low bone mass density (BMD) (osteoporosis and T-score <–2.5). The low serum level of vitamin D3 (<20 ng/mL) and low testosterone of <0.9 ng/mL had risk prediction (odds ratio) of 1.14 and 1.2, respectively, for abnormal BMD in SCD.

The oral delivery of insulin is a convenient and safe physiological route of administration for management of diabetes mellitus. In this study, we developed a poly-(styrene-co-maleic acid) (SMA) micellar system for oral insulin delivery to overcome the rapid degradation of insulin in the stomach, improve its absorption in the intestine, and provide a physiologically-relevant method of insulin to reach portal circulation. The insulin was encapsulated into SMA micelles in a pH-dependent process. The charge and size of the nanoparticles were determined by dynamic light scattering. The insulin loading of the nanoparticles was measured by HPLC. The transport of the SMA-insulin through biological membranes was assessed in vitro using Caco-2 cells, ex vivo rat intestinal section, and in vivo in a streptozotocin-induced diabetes mouse model. SMA-insulin micelles were negatively charged and had a mean diameter of 179.7 nm. SMA-insulin efficiently stimulated glucose uptake in HepG-2 hepatic cells and was transported across the Caco-2 epithelial cells in vitro by 46% and ex vivo across intestinal epithelium by 22%. The animal studies demonstrated that orally-administered SMA-insulin can produce a hypoglycemic effect up to 3 h after administration of one dose. Overall, our results indicate that SMA micelles are capable of the oral delivery of bioactive compounds like insulin and can be effective tools in the management of diabetes.

Intravenous paracetamol is a commonly administered analgesic and antipyretic in inpatient settings. Paracetamol is metabolized by cytochrome P450 (CYP) enzymes followed by conjugating enzymes to mainly glucuronide but to a lesser extent, sulphate metabolites, and oxidative metabolites. Single nucleotide polymorphisms (SNPs) in the CYP enzymes result in modified enzymatic activity. The present study was carried out to evaluate the prevalence of SNPs related to paracetamol metabolism and principal metabolites in critically ill patients, and those with chronic kidney disease. The present study is a cross-sectional study carried out in adults (>21 years) requiring intravenous paracetamol as part of their standard of care. Details regarding their demographics, and renal and liver function tests were collected. Blood was withdrawn for the analysis of paracetamol and their metabolites, and the SNPs of key CYP enzymes. Paracetamol/paracetamol glucuronide (P/PG), paracetamol/paracetamol sulphate (P/PS) and PG/PS were estimated. Acute liver injury (ALI) and renal dysfunction were defined using standard definitions. We observed a significant prevalence of SNPs in CYP1A2*1C, CYP3A4*3, CYP1A2*1K, CYP1A2*6, CYP2D6*10, and CYP2E1*2 amongst the 150 study participants. Those with CYP1A2*6 (CC genotype) were observed with significantly lower PG and PS concentrations, and a higher P/PS ratio; CYP2D6*10 (1/1 genotype) with a significantly lower PG concentration and a higher P/PG ratio; and CYP1A2*1K (CC genotype) was observed with a significantly higher PG/PS ratio. Good predictive accuracies were observed for determining the SNPs with the cut-off concentration of 0.29 μM for PS in determining CYP1A2*1K, 0.39 μM for PG and 0.32 μM for PS in determining CYP1A2*6 genotype, and 0.29 μM for PG in determining the CYP2D6*10 genotype. Patients with renal dysfunction were observed with significantly greater concentrations of paracetamol, PG and P/PS, and PG/PS ratios, with a lower concentration of PS. No significant differences were observed in any of the metabolites or metabolite ratios in patients with ALI. We have elucidated the prevalence of key CYP enzymes involved in acetaminophen metabolism in our population. Alterations in the metabolite concentrations and metabolic ratios were observed with SNPs, and in patients with renal dysfunction. Population toxicokinetic studies elucidating the dose-response relationship are essential to understand the optimized dose in this sub-population.

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of tumors that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. The mainstay of treatment remains chemotherapy, but the therapeutic outcome remains inadequate. This paper investigates the potential of a duocarmycin derivative, tafuramycin A (TFA), as a new and more effective chemotherapy agent in TNBC treatment. To this extent, we optimized the chemical synthesis of TFA, and we encapsulated TFA in a micellar system to reduce side effects and increase tumor accumulation. In vitro and in vivo studies suggest that both TFA and SMA–TFA possess high anticancer effects in TNBC models. Finally, the encapsulation of TFA offered a preferential avenue to tumor accumulation by increasing its concentration at the tumor tissues by around four times in comparison with the free drug. Overall, the results provide a new potential strategy useful for TNBC treatment.