New Insight into the Possible Roles of L-Carnitine in a Rat Model of Multiple Sclerosis.

OBJECTIVE: We investigated the effect of L-carnitine (LC) on cuprizone (Cup) demyelinating rat model and its possible underlying mechanisms. METHODS: Thirty male Sprague-Dawley (SD) rats were randomly allocated to three groups: the normal control group; the Cup group, in which Cup was administrated at a dose of 450 mg/kg per day orally via gastric gavage for 5 weeks; and the Cup + LC group, which received the same dose of Cup as the Cup group, except that the rats were treated additionally with LC 100 mg/kg/day orally for 5 weeks. The nerve conduction (NCV) in isolated sciatic nerves was measured; then, the sciatic nerves were isolated for H&E staining and electron microscope examination. The expression of myelin basic protein (MBP), IL-1ß, p53, iNOS, and NF-KB by immunohistochemistry was detected in the isolated nerves. A PCR assay was also performed to detect the expression of antioxidant genes Nrf2 and HO-1. In addition, the level of IL-17 was measured by ELISA. RESULTS: There was a significant reduction in NCV in the Cup group compared to normal rats (p < 0.001), which was significantly improved in the LC group (p < 0.001). EM and histopathological examination revealed significant demyelination and deterioration of the sciatic nerve fibers, with significant improvement in the LC group. The level of IL-17 as well as the expression of IL-1ß, p53, iNOS, and NF-KB were significantly increased, with significant reduction expression of MBP in the sciatic nerves (p < 0.01), and LC treatment significantly improved the studied parameters (p < 0.01). CONCLUSION: The current study demonstrates a neuroprotective effect of LC in a Cup-induced demyelinating rat model. This effect might be due to its anti-inflammatory and antioxidant actions.

Eid-al-Fitr festivity and Ramadan fasting attitude among individuals with diabetes from Saudi Arabia and Pakistan: a cross-sectional study.

OBJECTIVES: The present study aimed to assess the attitude of Saudi and Pakistani individuals with diabetes regarding Eid-al-Fitr festivities, exploring diabetes care during the month of Ramadan and these individuals' dietary patterns on Eid day. DESIGN: Cross-sectional study. SETTING: Jeddah (Saudi Arabia) and Karachi (Pakistan). PARTICIPANTS: Of the total 405 subjects, 204 individuals with diabetes from Saudi Arabia (SA) and 201 from Pakistan (Pak) were enrolled. DATA COLLECTION AND ANALYSIS: This survey-based study was carried out in SA and Pak after Eid-al-Fitr 2020. An online questionnaire was circulated via various social media platforms. The data analyses were performed using SPSS V.26. RESULTS: There were 80 subjects with type 1 diabetes mellitus (DM) and 325 subjects with type 2 DM. Among our study subjects, 73 were on insulin, 260 were on oral antidiabetics (OADs) and 72 were taking both OADs and insulin. Two-thirds of the participants, 276 (68%) visited their physicians before Ramadan. Many participants (175, 43.2%) broke their fast a day or more because of diabetes. Many participants consumed sugary food on Eid day. The use of chocolates, sugary foods and fresh juices on Eid-al-Fitr was higher in Saudi subjects than in Pakistani ones (p<0.001). Saudi subjects with diabetes adhered more strictly to medications during Ramadan than Pakistani subjects (p=0.01). Saudi participants were more compliant with monitoring DM during Eid-al-Fitr compared with Pakistani subjects. Many participants in both groups felt stressed or depressed and stated that their Eid celebrations were restrictive because of their DM conditions. CONCLUSIONS: Most Saudi and Pakistani participants enjoyed Eid celebrations by abstaining from dietary restrictions. The sugar consumption attitude during Eid day was not up to the mark. Many subjects broke their fasts for a day or more because of diabetes. Saudis were more vigilant in monitoring DM than Pakistanis during Eid-al-Fitr. Individuals with diabetes should consult their physicians before Ramadan for checkups and counselling.

Prevalence of uncorrected refractive errors among children aged 3-10 years in western Saudi Arabia.

OBJECTIVES: To determine the prevalence of uncorrected refractive errors (URE) among children 3-10 years and to affirm the necessity of a national school-based visual screening program for school-aged children. Methods: This retrospective cross-sectional study was conducted in Medina, Saudi Arabia in 2015. Children were selected through a multistage stratified random sampling from 8 kindergarten and 8 primary schools. Those included were screened to diagnose UREs using a visual acuity chart and an auto refractometer according to American guidelines. The prevalence and types of UREs were estimated. Results: Of the 2121 children enumerated, 1893 were examined, yielding a response rate of 89.3%. The prevalence of UREs was 34.9% (95% CI = 32.8%-37.1%), with significant differences in different age groups. The prevalence of astigmatism (25.3%) was higher compared to that of anisometropia (7.4%), hypermetropia (1.5%), and myopia (0.7%). Risk of uncorrected refractive error was positively associated with age, and this was noted in astigmatism, myopia, and anisometropia. In addition, the risk of hypermetropia was associated with boys and that of myopia was associated with girls. Conclusions: The prevalence of UREs, particularly astigmatism, was high among children aged 3-10 years in Medina, with significant age differences. Vision screening programs targeting kindergarten and primary schoolchildren are crucial to lessen the risk of preventable visual impairment due to UREs.

Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome.

AIMS/HYPOTHESIS: We sought to establish the molecular and pathological changes predisposing diabetic and non-diabetic patients to the development of carpal tunnel syndrome (CTS). METHODS: The posterior interosseous nerve (PIN) was biopsied in 25 diabetic and 19 non-diabetic patients undergoing carpal tunnel decompression for CTS. Detailed morphometric and immunohistological analyses were performed in the nerve biopsy. RESULTS: In diabetic patients median nerve distal motor latency was prolonged (p < 0.05 vs non-diabetic patients), PIN myelinated fibre density (p < 0.05), fibre area (p < 0.0001) and axon area (p < 0.0001) were reduced, the percentage of unassociated Schwann cell profiles (p < 0.0001) and unmyelinated axon density (p < 0.0001) were increased and the axon diameter was reduced (p < 0.0001). Endoneurial capillary basement membrane area was increased (p < 0.0001) in diabetic patients, but endothelial cell number was increased (p < 0.01) and luminal area was reduced (p < 0.05) in non-diabetic patients with CTS. There was no difference in the expression of hypoxia-inducible factor 1α between diabetic and non-diabetic patients with CTS. However, the expression of vascular endothelial growth factor A (VEGF) (p < 0.05) and its receptors VEGFR-1 (p < 0.01) and VEGFR-2 (p < 0.05) was significantly increased in diabetic patients, particularly those with type 1 diabetes, and related to the severity of nerve fibre pathology. CONCLUSIONS/INTERPRETATION: This study demonstrates increased nerve fibre and microvascular pathology in relation to enhanced expression of VEGF and its receptors in a non-compressed nerve in diabetic compared with non-diabetic patients with CTS. It therefore provides a potential molecular and pathological basis for the predisposition of diabetic patients to the development of CTS.

Diabetic retinopathy is associated with oxidative stress and mitigation of gene expression of antioxidant enzymes.

Type 2 diabetes is a metabolic disease associated with serious complications, including diabetic retinopathy (DR). The authors' main aim was to investigate biochemical parameters and the oxidative stress associated with the type 2 DR patients and to study gene expression of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) among patients with DR [DR(+)] compared with a control nondiabetic group. In all, 67 patients with DR included in this study were diabetic for more than 10 years. Among them, 22 patients were DR(+), and 45 patients did not have DR [DR(-)]. The subjects' age range was 14 years to 80 years old with diabetes duration range between 2 and 45 years. Body mass index (BMI) was 31.43 ± 5.94 and 32.33 ± 6.54, systolic blood pressure was 117.15 ± 18.16 mmHg and 126.15 ± 20.26 mmHg, diastolic blood pressure was 81.11 ± 10.55 mmHg and 82.77 ± 10.85 mmHg, HbA1c was 7.2 ± 1.1 and 8.19 ± 1.95, serum total cholesterol was 6.61 ± 1.11 and 4.11 ± 0.31, serum triglycerides were 3.52 ± 0.89 and 3.42 ± 0.79, serum low-density lipoprotein (LDL) was 2.12 ± 0.10 and 2.42 ± 0.15, high-density lipoprotein (HDL) was 2.66 ± 0.30 and 2.55 ± 0.21, SOD was 3.12 ± 0.87 and 1.53 ± 0.14, GPx was 11.14 ± 2.21 and 8.2 ± 1.84, CAT was 26.43 ± 3.34 and 9.60 ± 2.14, for DR(-) and DR(+) patients, respectively. SOD, GPx and CAT polymerase chain reaction (PCR) products of the DR(+) patients revealed the diminished expression of CAT gene followed by GPx and SOD genes. All were significant compared with the normal controls, P < 0.05. Linear regression analysis revealed a strong significant positive correlation between the retinopathy grade and the diastolic blood pressure, diabetes duration, hemoglobin A1c (HA1c)%, and fasting blood glucose (P < 0.001). A marginally significant positive correlation between the retinopathy grade and LDL-cholesterol was observed (P < 0.05), and a significant negative correlation between the retinopathy grade and total cholesterol was observed (P < 0.05). Poor glycemic control and alteration in mRNA gene expression of antioxidant enzymes are strongly associated with development of DR and the regular screening is mandatory for early detection and treatment.

Body weight reduction and metformin: Roles in polycystic ovary syndrome.

BACKGROUND AND OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common problem in women at fertile age. A prospective study was conducted to clarify the pathophysiological responses during an application of insulin sensitizer, metformin and weight reduction therapy at the Gynecology Center in Ohud hospital, in AL-Madinah AL-Munawarah, Kingdom of Saudi Arabia. METHODOLOGY: Twenty healthy women served as controls and 180 PCOS women divided into three groups participated in the study. First group was treated with Clomid citrate 100mg/day from the 2nd day of menses to the 6th day plus gonadotrophin from day three to the 13th. Group II was treated as group I plus 850mg metformin twice a day and group III was treated as group I plus weight reduction. Clinical symptoms, menstrual pattern, hirsutism, blood glucose, body mass index, waist-to-hip ratio, insulin, hormonal, and lipid profiles were assessed pre- and post treatment. Insulin resistance was calculated. RESULTS: PCOS women had significantly higher values than the healthy women in most of the measurements. Metformin and weight reduction therapy resulted in a significant decrease in the fasting insulin, glucose/insulin ratio and HOMA-IR. Metformin and weight reduction therapy resulted in a significant decrease in the lipid parameters, testosterone, LH/FSH ratio, SHBG, and prolactin levels. HOMA-IR was significantly higher in women with PCOS. HOMA-IR was positively correlated with testosterone, estradiol, TG, total cholesterol and LDL-cholesterol parameters, and negatively correlated with HDL-cholesterol and FSH levels. CONCLUSION: Metformin therapy and weight reduction had favorable influences on the basic metabolic and hormonal profiles in women with PCOS and that metformin and lifestyle modification (weight reduction via diet restriction or exercise) resulted in a significantly greater weight loss than hormonal therapy alone. Metformin and weight reduction therapy decreased also hyperandrogenism and insulin resistance.

Reassessment of the undergraduate educational environment in College of Medicine, Taibah University, Almadinah Almunawwarah, Saudi Arabia.

BACKGROUND: We reassessed the perception of all undergraduate students in Taibah medical college regarding the educational environment during the academic year 2010-2011 and compared it with the assessment carried out three years earlier in order to identify the change over time from previous assessment. METHOD: In the present prospective study, the validated 50-item Dundee Ready Education Environment Measure (DREEM) inventory was collected from medical students of basic phase (n = 302) and clinical phase (n = 222) and compared the scores of students' responses with those of previous assessment 3 years earlier. RESULTS: In the year 2007/2008 DREEM inventory scored 109.1/200 and scored 120.70/200 (p ≤ 0.0001) in the year 2010/2011. There was an interesting inclination of female students towards a more positively perceived learning environment as compared to male students (26/48 versus 24/48, p < 0.03). There were statistically significant differences in all domain components of DREEM between the academic years 2007/2008 and 2010/2011. CONCLUSIONS: DREEM helped pinpoint areas of change in students' perception regarding many aspects of the educational environment. It also helped to identify areas that are still in need of improvement by the college's administration and staff. DREEM inventory can be used to monitor change over time in the educational environment.

Reduced myelinated nerve fibre and endoneurial capillary densities in the forearm of diabetic and non-diabetic patients with carpal tunnel syndrome.

The underlying basis of carpal tunnel syndrome (CTS) and the basis of its increased incidence in diabetes are unknown. We have quantified pathology in an uncompressed nerve (posterior interosseous nerve, PIN) in the forearm between diabetic and non-diabetic patients with CTS and control subjects. In an age- and gender-matched series, 26 diabetic patients with CTS and 20 non-diabetic patients with CTS underwent biopsy of the PIN at the time of surgical carpal tunnel release. Control subjects consisted of ten PIN biopsies taken postmortem and three biopsies taken at the time of wrist surgery. We found PIN myelinated nerve fibre density significantly reduced in diabetic (mean 5,373/mm2 [95% confidence interval, 4,835­5,911]) and non-diabetic (6,617/mm2 [5,697­7,537]) patients with CTS compared to control subjects (9,109/mm2 [7,967­10,250], P < 0.001). Furthermore, diabetic patients had a significantly lower density than non-diabetic patients (P < 0.03). Endoneurial capillary density was also reduced in diabetic (58/mm2 [50­66]) and non-diabetic (67/mm2 [55­78]) patients compared to control subjects (86/mm2 [72­101], P < 0.02) with no difference between diabetic and non-diabetic patients with CTS. Our results suggest that a reduction in myelinated nerve fibre and capillary densities may predispose patients, particularly those with diabetes, to develop CTS.

Pathophysiology and treatment of painful diabetic neuropathy.

Diabetes is the most common cause of peripheral neuropathy, and painful diabetic neuropathy (PDN) affects approximately 30% of diabetic patients with neuropathy. It is extremely distressing for the patient and poses significant management difficulties because no treatment provides total relief, and side effects of therapy are a major limiting factor for titrating therapy. Understanding the pathogenesis of diabetic neuropathy may lead to the development of new treatments to prevent nerve damage, and a better understanding of the mechanisms that modulate pain may lead to more effective relief of painful symptoms. We provide an update on the pathogenesis, diagnosis, and treatment of PDN.

Recent developments in the assessment of efficacy in clinical trials of diabetic neuropathy.

A large number of measures may be employed in clinical practice and for epidemiologic studies to quantify and risk stratify diabetic patients with neuropathy. However, not all measures are suitable for assessing the benefits of therapeutic intervention. Therefore, for the purpose of this review we focus on measures that may be employed to define the efficacy of interventions in clinical trials of human diabetic neuropathy. Two major types of end points are used: 1) those that assess symptoms for defining efficacy in painful diabetic neuropathy, and 2) those that assess neurologic deficits that assess the effects of treatments that may prevent further degeneration or promote repair.