Expression of miRNAs-122, -192 and -499 in end stage renal disease associated with acute myocardial infarction.

INTRODUCTION: New diagnostic tools are needed to accurately detect acute myocardial infarction (AMI) in patients with end stage renal disease (ESRD) presenting with ischemic chest pain. We aimed in this study to investigate circulating miR-122, -192 and -499 expression levels in patients with AMI on top of ESRD and evaluate the potential of these miRNAs as blood-based biomarkers for AMI in patients with ESRD. MATERIAL AND METHODS: The study included 80 ESRD patients without AMI, 80 patients with ESRD associated with AMI and 60 healthy subjects. Assessment of microRNAs was done using SYBR Green based real-time PCR. RESULTS: Levels of miR-122 were 28-fold and 20-fold higher in controls than in ESRD patients with or without AMI respectively (p < 0.001), while no differences were detected between the two patient groups (p = 0.9). Levels of miR-192 showed a marked increase in ESRD patients with and without AMI compared to the control group (> 500-fold, > 8000-fold respectively, p ≤ 0.001). Patients who developed AMI had lower expression than ESRD patients without AMI (p < 0.001). Non-significant miR-499 elevation was found in ESRD patients without cardiac disease compared to the control group, while highly significant elevation of miR- 499 was demonstrated in ESRD patients who developed AMI compared to other ESRD patients and the control group (> 100-fold, > 350-fold respectively, p = 0.001). CONCLUSIONS: Altered expression of miR-122 and -192 may contribute in pathogenesis of ESRD. MiR-192 and -499 may serve as potential biomarkers for AMI in ESRD. Further studies are needed to correlate these miRNAs with disease progression and outcome.

The expression of microRNA 146a in patients with ischemic stroke: an observational study.

AIM: We conducted the present prospective study to assess the level of microRNA (miRNA) 146a in patients with ischemic stroke and its correlation with patients' characteristics. METHODS: We conducted an observational study that included adult patients (≥18 years old) who presented within 24 hrs after the onset of the symptoms of acute ischemic stroke. In addition, age- and sex-matched healthy volunteers were included as control group. The primary outcome in the present study was the difference in miRNA 146a expression between patients with ischemic stroke and control group participants. The expression of miRNA 146a was measured using quantitative real-time PCR. Quantitative real-time PCR amplification and analysis were performed using Rotor-Gene Q thermal cycler. RESULTS: The present study included 44 patients with ischemic stroke and 22 matched controls. Regarding the primary outcome of the present study, the median expression of miRNA 146a in patients with ischemic stroke was -1.98 fold (IQR -27.1-3.9) compared to 1.75 fold (IQR -2.25-5.27) in control group (P<0.001). However, the subgroup analysis showed that the expression of miRNA 146a was significantly downregulated in comatosed patients only (P<0.001). The expression of miRNA 146a correlated negatively with Glasgow Coma Scale score in comatose patients (r=-0.352, P=0.022). CONCLUSION: In conclusion, the expression of miRNA 146a is significantly downregulated in ischemic stroke patients. Further studies are needed to assess its diagnostic utility and therapeutic potentials.

Ferulic acid, a natural polyphenol, alleviates insulin resistance and hypertension in fructose fed rats: Effect on endothelial-dependent relaxation.

Ferulic acid (FER) is a polyphenolic compound contained in various types of fruits. It has a substantial therapeutic effect inhibitory activity against aldose reductase (AR) inhibition. In this study, we examined the effect of FER on fructose-fed rats in comparison to a standard AR inhibitor, zopolrestat (ZOP). We determined the protective role of FER against metabolic syndrome by examining serum insulin/Glucose levels, triglycerides (TGs), cholesterol and advanced glycation end product (AGE) in rats supplied with 10% fructose drinking water. In addition, blood pressure, vascular reactivity of isolated thoracic aortas and acetylcholine-induced NO were all evaluated to estimate the cardiovascular complications of metabolic syndrome (MetS) associated with fructose feeding. Animals were randomly divided into four groups: control, (+10% fructose, Fru), zopolrestat-treated fructose fed (Fru-zop) and ferulic acid-treated fructose fed rats (Fru-Fer). After 12 weeks of FER treatment, we found significant reduction in both hyperinsulinemia and elevated diastolic blood pressure associated with fructose-fed to levels comparable to those achieved with ZOP. Both FER and ZOP significantly augmented the impaired relaxation associated with fructose-fed, whereas neither showed any significant effect on the developed vasoconstriction. Isolated aortas from fructose-fed rats incubated with either FER or ZOP, reinstated normal relaxation response to acetylcholine (ACh). Furthermore, isolated aortas showed attenuated nitric oxide (NO) production following the addition of (ACh), while both FER and ZOP restored normal induction of NO. Taken together, the current study shows that, FER alleviated insulin resistance and hypertension associated with metabolic syndrome compared to the standard AR inhibitor (ZOP). This potential protective effect is at least mediated by restoring endothelial relaxation.

Aldose reductase inhibitors zopolrestat and ferulic acid alleviate hypertension associated with diabetes: effect on vascular reactivity.

This study investigated the effect of aldose reductase (AR) inhibitors on hypertension in diabetes. Diabetes was induced with streptozotocin, while AR inhibitors zopolrestat and ferulic acid were administered at 2 weeks after streptozotocin treatment and for 6 weeks afterwards. Then, blood pressure (BP) and serum level of glucose were determined. Concentration-response curves for phenylephrine (PE), KCl, and acetylcholine (ACh) were obtained in isolated aorta. In addition, ACh-induced NO and reactive oxygen species (ROS) generation in aorta and histopathology were examined. Compared with the control animals, diabetes increased diastolic and systolic BP. AR inhibitors reduced diastolic BP elevation without affecting the developed hyperglycaemia. Diabetes increased the contractile response of aorta to KCl, and decreased the relaxation response to Ach, while administering AR inhibitors prevented an impaired response to ACh. Incubation of aorta isolated from diabetic animals with AR inhibitors did not affect the impaired relaxation response to ACh. In addition, AR inhibitors negated the impaired Ach-stimulated NO generation seen in aorta isolated from diabetic animals. Furthermore, diabetes was accompanied with marked infiltration of leukocytes in aortic adventitia, endothelial cell pyknosis, and increased ROS formation. AR inhibitors reduced leukocyte infiltration and inhibited endothelial pyknosis and ROS formation. In conclusion, AR inhibitors negate diabetes-evoked hypertension via ameliorating impaired endothelial relaxation and NO production.

Audit of physicians' adherence to the antibiotic policy guidelines in Kuwait.

OBJECTIVE: To audit physicians' adherence to the local antibiotic policy guidelines in government hospitals in Kuwait. MATERIALS AND METHODS: The study was a retrospective review of patient records in nine hospitals between July 1 and December 31, 2008. Clinical notes and medication charts of the latest hospital admissions were checked for antibiotic prescribing. On the audit form, aspects of the prescribed antibiotic were benchmarked to the hospital antibiotic policy guidelines to evaluate adherence. RESULTS: Of 2,232 reviewed records, 1,112 (49.8%) patients had 1,528 antibiotic prescriptions. Patients who received antibiotics were significantly younger than those who did not (median age: 26.3 vs. 29.8 years, p < 0.001) and their hospital stay was significantly longer (median: 4 vs. 2 days, p < 0.001). The choice of an antibiotic was appropriate and matched the policy in 806 (52.7%) prescriptions. Of such appropriate antibiotics, adherence to route of administration was observed in 768/806 (95.3%), to dose in 758 (94%), to frequency in 746 (92.6%) and to duration in 608 (75.4%). Full adherence to all aspects of antibiotic choice, dose, route, frequency and duration was achieved in 464 (30.4%) prescriptions. In 382 (25%), the antibiotics administered were not indicated. CONCLUSION: There was low adherence to the local antibiotic policy guidelines. Physicians' antibiotic prescribing practices should be optimized. Adherence to, and update of, the policy is recommended.

Cinnamaldehyde protects from the hypertension associated with diabetes.

Here we investigated cinnamaldehyde (CA) effect on diabetes-induced hypertension. Insulin deficiency was induced by streptozotocin while, insulin resistance by fructose. Rats were left 8 weeks or 12 weeks after STZ or fructose administration respectively. CA (20 mg kg(-1)day(-1)) was daily administered in the last 6 weeks. Then, blood pressure (BP) was recorded. Isolated Aorta reactivity to phenylephrine (PE), KCl, acetylcholine (ACh) was studied as well as nitric oxide (NO) generation plus Ca(2+) influx. Insulin deficiency was associated with elevated BP, increased response to PE and KCl, decreased response to ACh and impaired NO generation. CA treatment prevented hyperglycemia and its associated impaired vascular reactivity. Insulin resistance was associated with elevated BP while, CA prevented this elevation. Insulin resistance increased response to PE and KCl, decreased response to ACh, while CA treatment normalized response to KCl and PE but not to ACh. Insulin resistance was accompanied with reduced NO generation but exaggerated Ca(2+) influx while CA restored normal Ca(2+) influx but did not affect NO generation. In conclusion, CA prevents development of hypertension in insulin deficiency and insulin resistance through normalization of vascular contractility in addition to its insulinotropic effect in insulin deficiency.