Histological and Immunohistochemical Basis of the Effect of Aminoguanidine on Renal Changes Associated with Hemorrhagic Shock in a Rat Model.

Acute kidney failure is the main cause of death among patients with severe trauma due to massive blood loss and hemorrhagic shock (HS). Renal cell injury is caused by tissue ischemia. Renal ischemia initiates a complex and interconnected chain of events resulting in cell injury and renal cell necrosis. Nitric oxide plays a crucial role in renal function and can be inhibited by aminoguanidine (AG). We studied whether AG can ameliorate pathological renal changes associated with HS syndrome in a rat model and explored the AG protection mechanism. Rats were intraperitoneally injected with heparin sodium and mean arterial blood pressure was monitored. Animals were divided into three groups: control (without hemorrhage), with or without intra-arterially injected AG; HS (blood continuously withdrawn or reinfused to maintain an MABP of 35-40 mmHg); and HS with AG. We found that AG decreased plasma concentrations of urea, creatinine, and nitrates; ameliorated histological changes of HS-induced rats; and decreased the expressions of inducible nitrogen oxide synthase (iNOS), proapoptotic protein (BAX), and vitamin D receptors (VDR). AG ameliorated kidney injury by inhibiting iNOS resulting in decreased BAX and VDR expressions. Therefore, a therapeutic strategy targeting AG may provide new insights into kidney injury during severe shock.

Physical activity and academic achievement among the medical students: A cross-sectional study.

AIMS: To explore physical activity (PA) habits among the medical students and examine the correlation with their grade point average (GPA) achievement at College of Medicine, King Saud University, Riyadh, Saudi Arabia. METHODS: A cross-sectional study was conducted among the medical students (n = 409), during the academic year 2012-2013. Students' physical activity habits were self-reported. GPA, body mass index (BMI) and body fat percent (BF%) were collected and analyzed with SPSS software. RESULTS: Out of 409 students, 193 (47.2%) students reported being physically active. Our result showed a significant positive association between students' PA habits and high-GPA achievement (χ(2 )= 10.65, p = 0.001). The greatest odds ratio of high GPA was found among the fourth year students (OR = 3.08, CI: 1.15-8.28, p = 0.025) and fifth year students (OR = 5.07, CI: 1.48-17.31, p = 0.010). In addition, significant association was found between the normal BMI and high-GPA achievers (χ(2 )= 8.30; p = 0.016). However, no statistically, significant association was found between BF% and GPA. CONCLUSIONS: The present study showed a positive associations was found between PA habits and high academic achievement. In addition, positive association was found between PA, obese students and GPA achievement. Therefore, there is a need for the establishment of physical activity education and public health programs to promote importance of PA in Saudi population.

No Evidence of Association of the Arg72Pro p53 Gene Polymorphism with Cancer Risk in the Saudi Population: a Meta-Analysis.

BACKGROUND: Earlier studies on the association between p53 codon 72 Arg>Pro polymorphism and cancer risk were inconclusive and conflicting for the Saudi population. Therefore, we performed a meta-analysis to investigate the relationship between the codon 72 Arg>Pro polymorphism and overall cancer risk in Saudi Arabia. MATERIALS AND METHODS: We searched all eligible published studies and data were pooled together to perform the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for homozygous, heterozygous, dominant and recessive genetic models. RESULTS: A total of five eligible published studies covering 502 cancer cases and 784 healthy controls were included in the meta-analysis. No publication bias was detected in this study. The results suggested that the variant (Pro vs Arg: p=0.960; OR=1.004, 95% CI=0.852-1.183), homozygous (Pro.Pro vs Arg.Arg: p=0.970; OR=1.006, 95% CI=0.729-1.390), heterozygous (Arg.Pro vs Arg.Arg: p=0.473; OR=0.783, 95% CI=0.402-1.527) carriers were not associated with overall cancer risk. Similarly, dominant (Pro.Pro+Pro.Arg vs Arg.Arg: p=0.632; OR=0.886, 95% CI=0.540-1.454) and recessive (Pro.Pro vs Pro.Arg+Arg.Arg: p=0.269; OR=1.163, 95%CI=0.890-1.521) models also did not indicate increased risk of cancer. CONCLUSIONS: The current meta-analysis suggests that the codon 72 Arg>Pro polymorphism of the p53 gene might not contribute to cancer susceptibility in Saudi population. Future well designed large case control studies are needed to validate our findings.

Students' perception towards the problem based learning tutorial session in a system-based hybrid curriculum.

OBJECTIVES: To evaluate students' perception towards the problem based learning (PBL) session in a system-based hybrid curriculum. METHODS: We conducted a cross-sectional study in the College of Medicine, King Saud University, Saudi Arabia at the end of the 2012-2013 academic year. The survey questionnaire was self-administered, and examined perceptions of PBL session benefits, appropriate running of sessions, and tutor's roles. RESULTS: Out of 510 students, 275 (53.9%) completed the questionnaire. Most of the students reported that PBL sessions were helpful in understanding basic sciences concepts (p=0.04). In addition, they agreed that PBL sessions increased their knowledge of basic sciences (p=0.01). Most students reported that PBL sessions encouraged self-directed learning, collaborative learning, and improved decision making skills. However, 54.5% of students reported lack of proper training before starting the PBL sessions, and only 25.1% of students agreed that the teaching staff are well prepared to run the sessions. Most students used the internet (93.1%), lecture notes (76.7%), and books (64.4%) as learning resources. Most students reported repetition of topics between PBL sessions and lectures (p=0.07). CONCLUSION: The study highlighted the significant role of PBL in a system-based hybrid curriculum and helped students improve their knowledge and different learning skills. Students and staff training is required before the utilizing the PBL as an instructional method.

Does coenzyme-Q have a protective effect against atorvastatin induced myopathy? A histopathological and immunohistochemical study in albino rats.

INTRODUCTION: In addition to their lipid-lowering effect, statins have pleiotropic effects that may extend their use to the treatment and prevention of various other diseases such as cancer, osteoporosis, multiple sclerosis, rheumatoid arthritis, type 2 diabetes, and Alzheimer's disease. Consequently, the number of patients taking statins is expected to increase. A side effect of statins, statin-induced myopathy, which may result from reduced muscular coenzyme Q10 levels, limits their use. The current study investigates if supplementing with CoQ10 could ameliorate statin induced myopathy. MATERIALS AND METHODS: Forty adult male albino rats were randomized into 4 groups, with 10 rats per group. The following was administered to the rats using oral gavage for 4 weeks: Group 1: 2 ml of 0.5% carboxymethyl cellulose once daily. Group 2: 100 mg/kg/ day coenzyme Q10 dissolved in 2 ml of cotton seed oil. Group 3: 10 mg/kg once daily atorvastatin dissolved in 0.5% carboxymethyl cellulose. Group 4: concomitantly received CoQ10 and atorvastatin similar to groups 2 and 3 respectively. Plasma creatine kinase levels were measured by using spectrophotometer. The right extensor digitorum longus muscle sections were stained for histological (Haematoxylin & Eosin, Masson trichrome and Phosphotungstic acid haematoxylin) and immunohistochemical (cytochrome C and Bax) examinations. Quantitative measures of cytochrome C and Bax were carried out using image analyzer. RESULTS: Atorvastatin induced increased total creatine kinase, skeletal muscle variations in the sizes and shapes, necrosis, disorganization, nuclear pyknosis, karyorrhexis, karyolysis, dismantled plasma membrane, excess collagen fibers and lipid deposition in addition to loss of cross striation. Atorvastatin increased the intensity of the immune-positive reactions of cytochrome C and Bax. These changes were ameliorated by concomitantly giving coenzyme Q10. CONCLUSION: CoQ10 may ameliorate atorvastatin induced skeletal muscle injury.

Research methodology workshops evaluation using the Kirkpatrick's model: translating theory into practice.

BACKGROUND: Qualitative and quantitative evaluation of academic programs can enhance the development, effectiveness, and dissemination of comparative quality reports as well as quality improvement efforts. OBJECTIVES: To evaluate the five research methodology workshops through assessing participants' satisfaction, knowledge and skills gain and impact on practices by the Kirkpatrick's evaluation model. METHODS: The four level Kirkpatrick's model was applied for the evaluation. Training feedback questionnaires, pre and post tests, learner development plan reports and behavioral surveys were used to evaluate the effectiveness of the workshop programs. RESULTS: Of the 116 participants, 28 (24.1%) liked with appreciation, 62 (53.4%) liked with suggestions and 26 (22.4%) disliked the programs. Pre and post MCQs tests mean scores showed significant improvement of relevant basic knowledge and cognitive skills by 17.67% (p ≤ 0.005). Pre-and-post tests scores on workshops sub-topics also significantly improved for the manuscripts (p ≤ 0.031) and proposal writing (p ≤ 0.834). As for the impact, 56.9% of participants started research, and 6.9% published their studies. The results from participants' performance revealed an overall positive feedback and 79% of participant reported transfer of training skills at their workplace. CONCLUSION: The course outcomes achievement and suggestions given for improvements offer insight into the program which were encouraging and very useful. Encouraging "research culture" and work-based learning are probably the most powerful determinants for research promotion. These findings therefore encourage faculty development unit to continue its training and development in the research methodology aspects.

What factors determine academic achievement in high achieving undergraduate medical students? A qualitative study.

BACKGROUND: Medical students' academic achievement is affected by many factors such as motivational beliefs and emotions. Although students with high intellectual capacity are selected to study medicine, their academic performance varies widely. OBJECTIVES: The aim of this study is to explore the high achieving students' perceptions of factors contributing to academic achievement. MATERIALS AND METHODS: Focus group discussions (FGD) were carried out with 10 male and 9 female high achieving (scores more than 85% in all tests) students, from the second, third, fourth and fifth academic years. During the FGDs, the students were encouraged to reflect on their learning strategies and activities. The discussion was audio-recorded, transcribed and analysed qualitatively. RESULTS: Factors influencing high academic achievement include: attendance to lectures, early revision, prioritization of learning needs, deep learning, learning in small groups, mind mapping, learning in skills lab, learning with patients, learning from mistakes, time management, and family support. Internal motivation and expected examination results are important drivers of high academic performance. Management of non-academic issues like sleep deprivation, homesickness, language barriers, and stress is also important for academic success. CONCLUSION: Addressing these factors, which might be unique for a given student community, in a systematic manner would be helpful to improve students' performance.

Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function.

Study of dual angiogenic/neurogenic growth factors among Saudi autistic children and their correlation with the severity of this disorder.

OBJECTIVE: To investigate the role of 2 angiogenic/neurogenic growth factors, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) in Saudi children with autism. METHODS: The study included a total of 60 children that included 20 controls and 40 patients with a confirmed diagnosis of autism. The study was conducted in the Department of Physiology, Faculty of Medicine, King Saud University, and in the Autism Research and Treatment Center, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between May 2010 and April 2011. Collected blood plasma samples were analyzed for VEGF and PDGF. RESULTS: The levels of VEGF showed a non-significant change in autistic children compared with the control children (p=0.065). The levels of PDGF were significantly higher in autistic children compared with the control children (p=0.01). Furthermore, this increase was significantly more pronounced in children with severe autism as compared with children with mild autism (p=0.001), and it was not correlated to the severity of the disorder. CONCLUSION: A rise in PDGF may contribute to the pathophysiology of the disorder, either alone or in synergy with other neurotrophic factors to induce an angiogenic-neuroprotective effect. Plasma VEGF has no causative or compensatory contribution to the pathology of this disorder.

F-ratio, a surrogate marker of carpal tunnel syndrome.

OBJECTIVE: To explore the correlation of F-ratio and F-wave minimal latency (FWML) in carpal tunnel syndrome (CTS). METHODS: This retrospective study was conducted from January 2006 to January 2007 at the clinical physiology lab, King Abdul-Aziz University Hospital, Riyadh, Saudi Arabia. Motor and sensory nerve conduction studies, FMW latencies of median and ulnar nerves, and F-ratio were carried out in 54 CTS patients and 30 controls. RESULTS: Out of 54 CTS patients, there were 14 were males (26%), and 40 females (74%), CTS was bilateral in 32 (59%), and unilateral in 22 (41%) patients. Fifty-one patients (94.4%) had involvement of the right hand, 28 patients (51.8%) had dyslipidemia and 20 patients (37%) had hypertension. The FWML (ms) in the right median nerve was 25.46+/-2.2, and 25.79+/-1.7 in the right ulnar nerve in the control group (p=0.5224), while it was 29.1+/-3.35 in the right median nerve and 26.46+/-4.35 in the right ulnar nerve in patients with CTS (p=0.0008). A similar statistically significant increase in the median nerve latency was observed in the left hand. A statistically significant reduction in the F-ratio was found consistently in all patients with CTS in both the hands (p=0.0001). CONCLUSION: The present study reveals prolongation of FWML in the median nerve, and a statistically significant reduction of F-ratio in all CTS patients. A significant inverse correlation was found between FWML and F-ratio in CTS patients. Both FWML and F-ratio support the diagnosis of CTS.

Assessment of respiratory muscles endurance in diabetic patients.

OBJECTIVE: Respiratory muscle endurance is of interest in pulmonary, critical care and many other areas of medicine. The maximal voluntary ventilation (MVV) test is an objective dynamic method for measuring the working capacity of respiratory muscles. Therefore, we designed the present study to determine the effect imposed by diabetes mellitus on respiratory muscle endurance in Saudi diabetic patients. METHODS: We conducted this study in the Department of Physiology, College of Medicine, King Khalid University Hospital and Diabetic Centre, King Abdul-Aziz University Hospital, Riyadh, Saudi Arabia during the year 2002-2004. In this study, we recruited 39 male diabetic patients and equal number of control subjects and all participants were non-smokers with age range of 23-71 years. The subjects were matched for age, height and weight. We determined the respiratory muscles endurance by a direct MVV test during inspiratory and expiratory phases of respiration by using a MP-100 student Bio Pac system and compared the results using a paired t-test. RESULTS: In inspiratory and expiratory phases of respiration, diabetic patients showed a significant reduction in the mean values of direct MVV test (p<0.001) relative to their matched controls. CONCLUSION: We conclude that in diabetic patients the respiratory muscles endurance is impaired by a decreased in MVV values. This decline in MVV further showed that the diabetic patients have a reduced inhaled and exhaled volumes during consecutive breaths.

Estrogen protects cardiac myogenic (H9c2) rat cells against lethal heat shock-induced cell injury: modulation of estrogen receptor alpha, glucocorticoid receptors, heat shock protein 70, and iNOS.

In the present study we have established that exposure of rat cardiac myoblasts (H9c2 cells) to 46 degrees C for 1 hour (lethal heat shock) resulted in optimal cell injury as determined by lactate dehydrogenase release. Pretreatment of H9c2 cells for 24 hours with 17beta-estradiol significantly protects myoblasts against subsequent lethal heat shock exposure in a concentration-dependent manner with maximum protection obtained at 1 microM of 17beta-estradiol. With Western blotting, it was observed that 17beta-estradiol-protected cells had significantly higher levels of the estrogen receptor alpha and inducible heat shock protein 70 (hsp70) as well as inducible nitric oxide synthase (iNOS) levels compared with lethal heat shock-exposed cells. In contrast, lethal heat shock-exposed cells had significantly higher levels of total cellular glucocorticoid receptors (GR), both cytoplasmic and nuclear, compared with 17beta-estradiol-protected cells. Immunofluorescence technique using confocal microscopy revealed nuclear localization of the glucocorticoid receptors (GR) in lethal heat shock-exposed H9c2 cells while 17beta-estradiol-protected cells had primarily extranuclear localization of GR. We conclude that (1) 17beta-estradiol protects H9c2 cells against lethal heat shock insult by a receptor-independent mechanism, and (2) the protective effects are likely mediated by modulation of GR, hsp 70, and iNOS expression.

Tamoxifen protects clonal mouse hippocampal (HT-22) cells against neurotoxins-induced cell death.

In the present work using an established clonal mouse hippocampal (HT-22) cell line, we have examined whether the estrogen antagonist tamoxifen antagonizes the observed neuroprotective effects of estrogen against glutamate and amyloid beta protein neurotoxicity. Results obtained suggest that like estrogen, tamoxifen protects HT-22 cells against both 5mM glutamate and 2 microM amyloid beta protein induced cell death in a concentration dependent manner. Optimum protection was obtained at 500 nM tamoxifen. Tamoxifen was found to offer more potent protection at this dose against amyloid beta protein induced neurotoxicity when compared with glutamate neurotoxicity. We were unable to detect either estrogen receptor (ER)--ER alpha or ER beta presence in HT-22 cells using western blot technique. However, amyloid beta protein treatment significantly increases total glucocorticoid receptors (GRs) as determined by western blot technique, while prior treatment with estrogen or tamoxifen followed by amyloid beta protein resulted in the reduction of total GRs to the levels comparable to that observed for the control untreated cells. In addition, using confocal immunoflourescence microscopy technique, we observed that 20 h of treatment with 2 microM amyloid beta protein resulted in enhanced nuclear localization of GRs in HT-22 cells as compared to control untreated cells or 500 nM tamoxifen alone treated cells. Interestingly, 500 nM tamoxifen treatments for 24h, followed by 20 h treatment with 2 microM amyloid beta protein resulted in dramatic reduction in GRs nuclear localization. In conclusion, tamoxifen (i) protects HT-22 cells against amyloid beta protein neurotoxicity and (ii) neuroprotective effect is independent of ERs.