Gender Differences in Prevalence of Sleepy Driving Among Young Drivers in Saudi Arabia.

Introduction: Sleepy driving is associated with Motor Vehicles Accidents (MVAs). In Saudi Arabia, previous studies have addressed this association among men only. Therefore, the aim of this study was to compare the prevalence of sleepy driving and associated factors between genders. Methods: In a cross-sectional study design, we offered a self-administered online questionnaire to 3272 participants from different regions of Saudi Arabia. The questionnaire included 46 questions covering sociodemographics, driving habits, sleeping habits, Epworth Sleepiness Scale, and Berlin questionnaire to assess the risk of sleep apnea. Univariable and multivariable logistic regression analyses were used to determine the significant factors associated with self-reported sleepy driving, defined as operating a motor vehicle while feeling sleepy in the preceding six months. Results: Of the 3272 invitees, 2958 (90%) completed the questionnaire, of which 1414 (48%) were women. The prevalence of sleepy driving in the preceding six months was 42% (men: 50% and women 32%, p<0.001). Specifically, participants reported the following: 12% had had to stop their vehicle due to sleepiness (men: 16.2% and women 7%, p<0.001), 12.4% reported near-miss accidents (men: 16.2% and women: 8.2%, p<0.001) and 4.2% reported an accident due to sleepiness (men: 4.3% and women: 4%, p=0.645). In multivariable analysis, being male, younger age, use of any type of medications, shift working, working more than 12 hours per day, driving duration of 3-5 hours per day, driving experience of more than 2 years, excessive daytime sleepiness and risk of having obstructive sleep apnea were all associated with increased likelihood of falling asleep while driving in the preceding 6 months. Conclusion: Sleepy driving and MVA are prevalent in both gender but was higher in men. Future public health initiatives should particularly focus on men, since men reported a greater likelihood of both sleep-related MVA and "near miss" events.

Effect of nocturnal hypoxemia on glycemic control among diabetic Saudi patients presenting with obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is a prevalent disease that is associated with an increased incidence of type II diabetes mellitus (DM) if left untreated. We aimed to determine the association between glycosylated hemoglobin (HbA1c) levels and both nocturnal hypoxemia and apnea-hypopnea index (AHI) among a Saudi patients with OSA. Methods: A cross-sectional study that enrolled 103 adult patients diagnosed with DM and confirmed to have OSA by full night attended polysomnography between 2018 and 2021. Those who presented with acute illness, chronic obstructive pulmonary disease (COPD)/restrictive lung diseases causing sleep-related hypoxemia, or no available HbA1c level within 6 months before polysomnography were excluded from the study. Univariate and multivariate linear regression analyses between HbA1c levels and parameters of interest were tested. Results: Sixty-seven (65%) of the studied population had uncontrolled DM (HbA1c ≥7%). In univariate regression analysis, there was a significant positive association between HbA1c, and sleep time spent with an oxygen saturation below 90% (T90), female gender, and body mass index (BMI) (p<0.05) but not AHI, or associated comorbidities (p>0.05). In the multivariate analysis, HbA1c was positively associated with increasing T90 (p<0.05), and ODI (p<0.05), but not with AHI (p>0.05). Conclusion: Nocturnal hypoxemia could be an important factor affecting glycemic control in patients with OSA suffering from DM irrespective of the severity of both diseases.

Association Between FeNO, Total Blood IgE, Peripheral Blood Eosinophil and Inflammatory Cytokines in Partly Controlled Asthma.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a convenient to use biomarker of airway inflammation. However, the mutual relationship between FeNO, peripheral blood eosinophil, total immunoglobulin E (IgE) and inflammatory cytokines showed some controversy. OBJECTIVE: This study was carried out to determine the accuracy of peripheral blood eosinophil and total IgE to detect eosinophilic airway inflammation as determined by two FeNO cutoff points. The correlation between FeNO, peripheral blood eosinophil, total IgE and certain inflammatory cytokines was also examined. METHODS: Seventy-six patients with partly controlled asthma performed the following tests on the same day: FeNO, pulmonary function tests (PFTs), peripheral blood eosinophils, total IgE, and inflammatory cytokine assay. The correlation between these markers was investigated and the diagnostic accuracy of peripheral blood eosinophils and total IgE to identify eosinophilic asthma phenotype was calculated using receiver operating characteristics area under the curve (ROC AUC). RESULTS: FeNO was positively correlated with percentage of blood eosinophils (r=0.276, p=0.017) and total blood IgE (r=0.3647; p=0.0013). No relationship between FeNO and serum inflammatory cytokines was detected. AUC of blood eosinophils and total IgE were 57% and 64% at FeNO ≥25 ppb and were 67% and 64% at FeNO >50, respectively. The higher predictive ability was detected at FeNO >50 ppb where the best cutoff point for blood eosinophil % was ≥4.0% (sensitivity 66.7%, specificity 60.0%) and the best cutoff point for total IgE was ≥350 (sensitivity 66.7%, specificity 63.6%). CONCLUSION: In patients with partly controlled asthma, peripheral blood eosinophil and total IgE showed equal useful accuracy in predicting eosinophilic airways. However, higher predictive values were reported at FeNO level >50 ppb. FeNO was positively correlated with peripheral blood eosinophil, total IgE but not with any of the studied cytokines.

The Effect of Listening to Holy Quran Recitation on Weaning Patients Receiving Mechanical Ventilation in the Intensive Care Unit: A Pilot Study.

Mechanical ventilation (MV) causes high level of stress in hospitalized patients. Weaning is the gradual process of decreasing ventilator support that in turn lead to termination of MV and increased respiratory effort, which may exacerbate symptoms and prolong MV. This study aimed to investigate the effect of listening to Holy Quran recitation (HQR) as a non-pharmacological intervention in patients during weaning from mechanical ventilation. This is a randomized controlled trial in which 55 patients admitted in the intensive care unit (ICU) and on mechanical ventilation were recruited. Patients were divided into experimental (case) and control group. In the experimental group, patients received 30 min of HQR, whereas in the control group, patients had 30 min of rest in bed before the start of the weaning. The physiological and/or clinical parameters of weaning were recorded. These parameters include rapid shallow breathing index, respiratory rate, heart rate, oxygen saturation, exhaled carbon dioxide, and blood pressure. The baseline demographic data for groups were presented in tables. The mean age was 54 ± 0.5 years for the experimental and 56.4 ± 18.5 years for the control groups. The physiological and clinical parameters were compared between case and control and found no significant difference. The preliminary findings of this pilot study suggest that there is no negative effect of HQR on weaning patients from mechanical ventilation in the ICU. The results also outline and explorthe possible utility of HQR further in ICU patients as an intervention in weaning patients off from ventilator in the ICU. Although there remains much to be done, our work generates important findings in the field of critical care management.

Noninvasive ventilation utilization in the Kingdom of Saudi Arabia: Results of a national survey.

INTRODUCTION: Noninvasive ventilation (NIV) has been extensively used globally and is often administered as the first-line treatment. Currently, data regarding the utilization of NIV in the Kingdom of Saudi Arabia (KSA) is scarce. The present study aimed to assess and quantify the utilization of NIV in clinical practice across the KSA and investigate obstacles that may cause NIV underutilization. METHODS: A web-based survey composed of a 31-item, self-administered questionnaire was developed and validated. The questionnaire was designed to obtain general information about each hospital, availability of NIV practice, use of NIV, and obstacles that can hinder NIV use in clinical settings; the survey was sent to senior respiratory therapists (RTs) of 76 hospitals. Descriptive statistics were used to analyze the data. RESULTS: Sixty-one hospitals (80.3%) responded to the survey (47 governmental and 14 private). NIV was available in all hospitals and all the Intensive Care Units. The majority of RTs (85%) reported having a good experience with NIV, with a confidence rate of 60%; however, only 22% of the RTs had received formal training. Although NIV setup was the sole responsibility of RTs, only 69% participated in NIV management. Moreover, 72% of hospitals had an NIV setup protocol in place. However, 50% of them lacked a protocol for NIV failure. NIV protocols for specific indications were present in 64% of the hospitals: 47.2% for monitoring and 42% for weaning. The perceived efficiency of NIV practice was low in the medical wards, with a <49% success rate in 39% of the hospitals. Shortage of staff and lack of formal training were the most common reasons for NIV underutilization. CONCLUSION: The efficiency of NIV in the KSA was low. The RTs expressed moderate confidence in administering NIV. Lack of appropriate exposure and formal training could have negative impacts on NIV practice.

Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populations.

BACKGROUND: Genome wide association studies of patients with European descent have identified common variants associated with risk of reduced estimated glomerular filtration rate (eGFR). A panel of eight variants were selected to evaluate their association and prevalence in a Saudi Arabian patient cohort with chronic kidney disease (CKD). METHODS: Eight genetic variants in four genes (SHROOM3, MYH9, SLC7A9, and CST3) were genotyped in 160 CKD patients and 189 ethnicity-matched healthy controls. Genetic variants were tested for association with the development of CKD (eGFR < 60 ml/min/1.73m2) and effects were compared with results obtained from 133,413 participants in the CKD genetics consortium. Multivariable regression was used to evaluate the role of these eight variants in improving prediction of CKD development. RESULTS: All eight variants were present in Saudi populations with minor allele frequency ranging from 16 to 46%. The risk variant in all four genes demonstrated the same direction of effect as observed in European populations. One variant, rs4821480, in MYH9 was significantly associated with increased risk of development of CKD (OR = 1.69, 95% CI 1.22-2.36, P = 0.002), but the additional variants were not statistically significant given our modest sample size. CONCLUSIONS: CKD risk variants identified in European populations are present in Saudis. We did not find evidence to suggest heterogeneity of effect size compared to previously published estimates in European populations. Multivariable logistic regression analysis showed a statistically significant improvement in predicting the CKD using models with either FGF23 and vitamin D or FGF23, vitamin D level, and MYH9 genotypes (AUC = 0.93, 95% CI 0.90-0.95, P <  0.0001).

Acute Kidney Injury in Critically Ill Patients: A Prospective Randomized Study of Tidal Peritoneal Dialysis Versus Continuous Renal Replacement Therapy.

Few studies have discussed the role of peritoneal dialysis (PD) in managing acute kidney injury (AKI) in critically ill patients. The present study compares the outcome of AKI in intensive care unit (ICU) patients randomized to treatment with tidal PD (TPD) or continuous venovenous hemodiafiltration (CVVHDF). One hundred and twenty-five ICU patients with AKI were randomly allotted to CVVHDF, (Group A, N = 62) or TPD, (group B, N = 63). Cause and severity of renal injury were assessed at the time of initiating dialysis. The primary outcome was hospital mortality at 28 days, and secondary outcomes were time to recovery of renal function, duration of stay in the ICU, metabolic and fluid control, and improvement of sensorial and hemodynamic parameters. No statistically significant differences were observed between groups in regard to patients' characteristics. The survival at 28 days was significantly better in the patients treated with TPD when compared to CVVHDF (69.8% vs. 46.8%, P < 0.01). Infectious complications were significantly less (P < 0.01) in the TPD group (9.5%) when compared to the CVVHDF group (17.7%). Recovery of kidney function (60.3% vs. 35.5%), median time to resolution of AKI and the median duration of ICU stay of 9 days (7-11) vs. 19 days (13-20) were all in favor of TPD (P < 0.01). This study suggests that there are better outcomes with TPD compared to CRRT in the treatment of critically ill patients with AKI.

Survey of Respiratory Care Professionals' Knowledge in Early Mobilization: A Pilot Study.

Early mobilization (EM) is practiced for intensive care unit (ICU) patients in many hospitals in the Eastern Province in Saudi Arabia. Respiratory care professionals' knowledge about using EM was, therefore, surveyed and investigated to improve and update its practice and ultimately to develop related regulations and policies. A survey including 156 respiratory care professionals was conducted using a validated questionnaire. The focus was on collecting information on participants' relevant backgrounds and on proper use of EM. Knowledge and proper use of EM were calculated in relation to participants' demographic and professional characteristics. The statistical analysis using analysis of variance and Student t-test showed that factors that affected knowledge of EM were the respiratory care professional's age, gender, nationality, and years of experience in intensive care medicine. How many patients these professionals treated using EM also significantly correlated with their knowledge of EM. The survey showed the extent of respiratory care professionals' knowledge about the proper use of EM. More importantly, the survey also identified important shortfalls in practice of some experienced medical practitioners.

The ­α3.7 deletion in α­globin genes increases the concentration of fetal hemoglobin and hemoglobin A2 in a Saudi Arabian population.

The regions of Al­Qatif and Al­Ahssa in the Eastern Province of Saudi Arabia are known for their high prevalence of hemoglobinopathies, including ß­thalassemia and sickle cell anemia. Previously, the α­gene deletion has been demonstrated as highly prevalent among populations residing in these two regions. The present study was conducted in order to investigate the implications of the α­globin gene deletion on fetal hemoglobin (HbF) and hemoglobin α2 (HbA2) concentrations in patients with transfusion­dependent ß­thalassemia. A total of 166 Saudi patients with transfusion­dependent ß­thalassemia and 337 healthy Saudi patients were included in the study. The ­α3.7, ­α4.2, -­FIL, -­SEA, -­MED and -­(20.5) gene deletions were identified using multiplex α­globin deletion polymerase chain reaction. The present study revealed that the ­α3.7 gene deletion is the most prevalent (43.5%) in the Saudi populations that were analyzed and is characterized by the deletion of 3,804 base pairs. Numerous genotypes, namely ­3.7α2/α1α2, ­3.7α2/α1α12, ­3.7α2/­3.7α2, ­3.7α2HphI/α1α2HphI, ­3.7α2/α1­4.2, ­3.7α2/α1polyA­1α2, ­3.7α12/α1α12, ­­FIL/­3.7α2 and ­3.7α2/­3.7α2Hb Villiers le Bel were also identified in the investigated population. Furthermore, a gradual increase in the concentration of HbF and HbA2 in patients with ß­thalassemia and the number of α­gene deletions was demonstrated; whereas in healthy patients the level of HbA2 was demonstrated to decrease as the number of α­gene deletions increased. Therefore, it can be concluded that the high HbF concentration in the present study is predominantly associated with other mutations associated with ß­thalassemia rather than α­globin deletions. Furthermore, the results of the present study also revealed novel α­gene deletion genotypes prevalent in the population studied, namely α1α2/α1α2HphI, α1α2HphI/α1α2HphI, α1α2/α1α2Hb Handsworth, ­3.7α2HphI/α1α2HphI, ­3.7α2/­3.7α2Hb Villiers le Bel and ­-MED/α1α2HphI.

Therapeutic effect of carnosine in rat model of experimental liver carcinogenesis.

The possible anticancer effect of carnosine versus doxorubicin was investigated against hepatocellular carcinoma (HCC) induced by trichloroacetic acid (TCA) (500mg/kg/day, p.o., for 5days) in rats. Following induction of HCC, rats treated with either carnosine (10mg/kg/day, i.p.), or doxorubicin (2.5mg/kg, i.p., once weekly), for 2 weeks. Carnosine significantly decreased serum alanine aminotransferase, and hepatic lipid peroxidation, nitric oxide, tumor necrosis factor-α, and nuclear factor-κB p65 unit, and significantly increased liver total antioxidant status in TCA-challenged rats. The effects of doxorubicin on oxidative, nitrative, and inflammatory biomarkers were less significant than carnosine. However, both carnosine and doxorubicin significantly induced liver tissue apoptotic biomarkers, Bax, cytosolic cytochrome C, and caspase-3, in a comparable manner. Additionally, carnosine and doxorubicin reduced the histopathological dysplastic changes, and alpha-fetoprotein expression in liver of rats with HCC. It was concluded that carnosine significantly protected against TCA-induced liver carcinogenesis in rats, through its antioxidant, antinitrative, and anti-inflammatory effects, and induction of apoptosis.

A phased SNP-based classification of sickle cell anemia HBB haplotypes.

BACKGROUND: Sickle cell anemia causes severe complications and premature death. Five common ß-globin gene cluster haplotypes are each associated with characteristic fetal hemoglobin (HbF) levels. As HbF is the major modulator of disease severity, classifying patients according to haplotype is useful. The first method of haplotype classification used restriction fragment length polymorphisms (RFLPs) to detect single nucleotide polymorphisms (SNPs) in the ß-globin gene cluster. This is labor intensive, and error prone. METHODS: We used genome-wide SNP data imputed to the 1000 Genomes reference panel to obtain phased data distinguishing parental alleles. RESULTS: We successfully haplotyped 813 sickle cell anemia patients previously classified by RFLPs with a concordance >98%. Four SNPs (rs3834466, rs28440105, rs10128556, and rs968857) marking four different restriction enzyme sites unequivocally defined most haplotypes. We were able to assign a haplotype to 86% of samples that were either partially or misclassified using RFLPs. CONCLUSION: Phased data using only four SNPs allowed unequivocal assignment of a haplotype that was not always possible using a larger number of RFLPs. Given the availability of genome-wide SNP data, our method is rapid and does not require high computational resources.

Epigallocatechin-3-gallate counters cisplatin toxicity of rat testes.

CONTEXT: Epigallocatechin-3-gallate (EG), the main active flavonoid in green tea, has well-known anti-inflammatory, antioxidant, and anti-apoptotic activities. OBJECTIVE: The EG protection against testicular injury induced by cisplatin was studied in Sprague-Dawley rats. MATERIALS AND METHODS: Cisplatin (10 mg/kg, i.p) was given as a single injection to rats. EG was given at 40 and 80 mg/kg/day, i.p., for 5 days, starting the same day of cisplatin insult. Serum testosterone, and testicular malondialdehyde, total antioxidant status, nitric oxide, interleukin-6, interleukin-1ß, cytochrome C, Bax/Bcl-2 ratio, and caspase-3 were measured. In addition, testicular histopathological examination and immunohistochemical expression of testicular tumour necrosis factor-α were evaluated. RESULTS: Cisplatin, compared to the control, significantly decreased serum testosterone (6.48 ± 0.7 vs. 50.8 ± 4.91 ng/10 mL), and testicular tissue antioxidant status (17.3 ± 1.21 vs. 64.12 ± 5.4 µmol/g), and significantly increased interleukin-6 (85.81 ± 6.11 vs. 38.2 ± 2.79 pg/100 mg), interleukin-1ß (98.09 ± 8.31 vs. 32.52 ± 2.08 pg/100 mg), malondialdehyde (74.5 ± 5.88 vs. 23.8 ± 1.91 nmol/g), nitric oxide (104.98 ± 8.5 vs. 52.68 ± 5.12 nmol/100 mg), cytochrome C (5.97 ± 0.33 vs. 1.6 ± 0.99 ng/mg protein), Bax/Bcl-2 ratio (4.01 ± 0.38 vs. 0.71 ± 0.0), and caspase-3 (3.2 ± 0.21 vs. 0.98 ± 0.08 O.D. 405 nm) in rat testes. EG (40 and 80 mg/kg, respectively) caused significant increases of serum testosterone (33.9 ± 2.89 and 47.88 ± 4.4 ng/10 mL), and testicular antioxidant status (47.1 ± 3.92 and 58.22 ± 3.58 µmol/g), and significant decreases of interleukin-6 (57.39 ± 4.2 and 48.18 ± 3.98 pg/100 mg), interleukin-1ß (65.12 ± 5.88 and 41.96 ± 3.51 pg/100 mg), malondialdehyde (42.3 ± 3.9 and 28.67 ± 2.49 nmol/g), nitric oxide (70.6 ± 6.79 and 61.31 ± 5.18 nmol/100 mg), cytochrome C (3.4 ± 0.27 and 2.21 ± 0.18 ng/mg protein), Bax/Bcl-2 ratio (1.49 ± 0.14 and 1.1 ± 0.09), and caspase-3 (2.1 ± 0.17 and 1.48 ± 0.13 O.D. 405 nm) in testes of cisplatin-treated rats. Additionally, both doses of EG significantly ameliorated the histopathological injury and reduced tumour necrosis factor-α expression in rat testes. CONCLUSION: EG can afford testicular protection in cisplatin-challenged rats by its antioxidant, antinitrative, anti-inflammatory and antiapoptotic effects.

Existence of HbF Enhancer Haplotypes at HBS1L-MYB Intergenic Region in Transfusion-Dependent Saudi ß-Thalassemia Patients.

Background and Objectives. ß-Thalassemia and sickle cell disease are genetic disorders characterized by reduced and abnormal ß-globin chain production, respectively. The elevation of fetal hemoglobin (HbF) can ameliorate the severity of these disorders. In sickle cell disease patients, the HbF level elevation is associated with three quantitative trait loci (QTLs), BCL11A, HBG2 promoter, and HBS1L-MYB intergenic region. This study elucidates the existence of the variants in these three QTLs to determine their association with HbF levels of transfusion-dependent Saudi ß-thalassemia patients. Materials and Methods. A total of 174 transfusion-dependent ß-thalassemia patients and 164 healthy controls from Eastern Province of Saudi Arabia were genotyped for fourteen single nucleotide polymorphisms (SNPs) from the three QTL regions using TaqMan assay on real-time PCR. Results. Genotype analysis revealed that six alleles of HBS1L-MYB QTL (rs9376090C p = 0.0009, rs9399137C p = 0.008, rs4895441G p = 0.004, rs9389269C p = 0.008, rs9402686A p = 0.008, and rs9494142C p = 0.002) were predominantly associated with ß-thalassemia. In addition, haplotype analysis revealed that haplotypes of HBS1L-MYB (GCCGCAC p = 0.022) and HBG2 (GTT p = 0.009) were also predominantly associated with ß-thalassemia. Furthermore, the HBS1L-MYB region also exhibited association with the high HbF cohort. Conclusion. The stimulation of HbF gene expression may provide alternative therapies for the amelioration of the disease severity of ß-thalassemia.

Effect of Nigella sativa supplementation on lung function and inflammatory mediatorsin partly controlled asthma: a randomized controlled trial.

BACKGROUND: Nigella sativa and its derivatives have been reported to have anti-inflammatory and bronchodilator effects, but the effects have been evaluated in only a few clinical studies. OBJECTIVES: To determine the effect of N sativa supplementation on inflammation of the airways and limitation of airflow in partly controlled asthma patients. DESIGN: Single-blind, placebo-controlled, randomized study. SETTING: Asthma and allergy clinic of a university hospital in eastern Saudi Arabia. PATIENTS AND METHODS: Patients were divided into three groups. A control group (n=24) received the placebo, while NS-1 and NS-2 groups (n=26 each) received 1 and 2 g/day of N sativa, respectively, for 3 months along with maintenance inhaled therapy. MAIN OUTCOME MEASURE(S): Asthma control test (ACT) score, fractional exhaled nitric oxide (FeNO), peak expiratory flow (PEF) variability and other pulmonary function tests, IgE, serum cytokines, and frequency of exacerbations. RESULTS: FEF25-75% and FEV1 (% predicted) increased significantly (P < .05) at both 6 and 12 weeks in the NS-2 group. PEF variability significantly improved in both NS-1 and NS-2 groups at 6 and 12 weeks as compared with the controls (P < .05). FeNO and serum IgE decreased significantly after 12 weeks in both the NS-1 and NS-2 groups vs baseline (P < .05). Both doses of N sativa produced a significant increase in the serum IFN-gamma at 12 weeks vs baseline (P < .05) as well as a significant improvement in the ACT score at 6 and 12 weeks vs baseline (P < .001, < .01). Significantly fewer patients had exacerbations in the NS-1 group (P < .05). CONCLUSION: N sativa supplementation with inhaled maintenance therapy improves some measures of pulmonary function and inflammation in partly controlled asthma. LIMITATIONS: No bronchoalveolar lavage or sputum samples taken for measurement of asthma markers. ISRCTN registry: ISRCTN48853858 DOI 10.1186/ISRCTN48853858.

A candidate transacting modulator of fetal hemoglobin gene expression in the Arab-Indian haplotype of sickle cell anemia.

Fetal hemoglobin (HbF) levels are higher in the Arab-Indian (AI) ß-globin gene haplotype of sickle cell anemia compared with African-origin haplotypes. To study genetic elements that effect HbF expression in the AI haplotype we completed whole genome sequencing in 14 Saudi AI haplotype sickle hemoglobin homozygotes-seven selected for low HbF (8.2% ± 1.3%) and seven selected for high HbF (23.5% ± 2.6%). An intronic single nucleotide polymorphism (SNP) in ANTXR1, an anthrax toxin receptor (chromosome 2p13), was associated with HbF. These results were replicated in two independent Saudi AI haplotype cohorts of 120 and 139 patients, but not in 76 Saudi Benin haplotype, 894 African origin haplotype and 44 AI haplotype patients of Indian origin, suggesting that this association is effective only in the Saudi AI haplotype background. ANTXR1 variants explained 10% of the HbF variability compared with 8% for BCL11A. These two genes had independent, additive effects on HbF and together explained about 15% of HbF variability in Saudi AI sickle cell anemia patients. ANTXR1 was expressed at mRNA and protein levels in erythroid progenitors derived from induced pluripotent stem cells (iPSCs) and CD34+ cells. As CD34+ cells matured and their HbF decreased ANTXR1 expression increased; as iPSCs differentiated and their HbF increased, ANTXR1 expression decreased. Along with elements in cis to the HbF genes, ANTXR1 contributes to the variation in HbF in Saudi AI haplotype sickle cell anemia and is the first gene in trans to HBB that is associated with HbF only in carriers of the Saudi AI haplotype. Am. J. Hematol. 91:1118-1122, 2016. © 2016 Wiley Periodicals, Inc.

Nephroprotection of punicalagin in rat model of endotoxemic acute kidney injury.

The potential nephroprotection of punicalagin (PNG) against lipopolysaccharide (LPS)-induced acute kidney injury in rats was investigated. Rats received a single i.v. dose of LPS (5 mg/kg), and treated with PNG (50 mg/kg, i.p.), 1 h before, and 1 h following LPS administration. LPS caused significant increases of serum creatinine and neutrophil gelatinase-associated lipocalin. LPS also resulted in significant increases in interleukin-18, tumor necrosis factor-α, interleukin-6, malondialdehyde, nitric oxide, Bax/Bcl-2 ratio and myeloperoxidase, inducible nitric oxide synthase, caspases 3, 8 and 9 activities, and a significant decrease in total antioxidant capacity in kidney tissues. PNG significantly ameliorated the alterations in the measured parameters. Additionally, PNG attenuated the histopathological injury and reduced kidney injury molecule-1 expression in kidneys of rats that received LPS. It was concluded that PNG ameliorated endotoxemic acute kidney injury in rats by counteracting inflammation, oxidative/nitrative stress and apoptosis.

Punicalagin alleviates hepatotoxicity in rats challenged with cyclophosphamide.

This study investigated the possible hepatoprotection of punicalagin in rats received cyclophosphamide (20mg/kg/day, i.p., for 7 days). Punicalagin given at two doses, 15 and 30mg/kg/day, p.o., for 7 days, starting the same day of cyclophosphamide administration. Punicalagin significantly and dose-dependently reduced the elevations of serum alanine aminotransferase, and liver nuclear factor-κB p65, tumor necrosis factor-α, interleukin-1ß, malondialdehyde, nitric oxide, Bax/Bcl-2 ratio, inducible nitric oxide synthase, caspases 3 and 9 activities, and prevented the decrease of hepatic total antioxidant capacity. Punicalagin also attenuated the histopathological liver tissue damage, and decreased cyclooxygenase-2 expression in liver of rats received cyclophosphamide in a dose-dependent manner. It was concluded that punicalagin protected rat liver against cyclophosphamide toxicity by inhibiting oxidative/nitrosative stress, inflammation, and apoptosis.