Abdullah S. Assiri

Influence of ellagic acid on prostate cancer cell proliferation: A caspase–dependent pathway

OBJECTIVE To evaluate the effect of allagic acid treatment on the cell viability of human prostate cancer cells. METHODS Ellagic acid (10-100 mol/L) treatment (48 h) of human prostate carcinoma PC3 cells was found to result in a dose-dependent inhibition of cell growth and apoptosis of PC3 cells as assessed by MTT assay, western blotting, flow cytometry and confocal microscopy. RESULTS We observed that ellagic acid treatment of PC3 cells resulted in a dose dependent inhibition of cell growth/cell viability. This ellagic acid caused cell growth inhibition was found to be accompanied by induction of apoptosis, as assessed by the cleavage of poly (ADP-ribose) polymerase (PARP) and morphological changes. Further, induction of apoptosis accompanied a decrease in the levels of antiapoptotic protein Bcl-2 and increase in proapoptotic protein Bax, thus shifting the Bax: Bcl-2 ratio in favor of apoptosis. Ellagic acid treatment of PC3 cells was also found to result in significant activation of caspases, as shown by the dose dependent decrease in the protein expression of procaspase-3, -6, -8 and -9. This ellagic acid-mediated induction of apoptosis was significantly (80%-90%) inhibited by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethylketone (Z-VAD-FMK). Thus these data suggested an essential role of caspases in ellagic acid-mediated apoptosis of PC3 cells. CONCLUSIONS It is tempting to suggest that consumption of tropical pigmented fruits and vegetables could be an effective strategy to combat prostate cancer.

Immunochemical Studies on Catechol-Estrogen Modified Plasmid: Possible Role in Rheumatoid Arthritis

IntroductionIncreased concentrations of estrogen metabolites (catecholestrogens) have been found in rheumatoid arthritis (RA) but the exact patho-etiology remains elusive.MethodsThe binding of antibodies from the sera of RA patients and control subjects to native and modified DNA was studied by direct binding and inhibition ELISA, quantitative precipitin titration. Experimentally induced antibodies were also checked to detect oxidative lesions in the DNA as well as for the estimation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in different fluids of RA.ResultsAnti-DNA IgG from RA sera, exhibited increased recognition of modified DNA than native DNA (nDNA; P < 0.001). The relative affinity of anti-DNA antibodies for modified and nDNA was in the order of 1.85 × 10−7, 1.23 × 10−7, and 1.2 × 10−6. Samples of DNA from RA patients showed a significant inhibition in the induced antibody activity in comparison to DNA isolates from controls (P < 0.001). The concentration of 8-OHdG evaluated by induced antibody in RA patients was found to be significantly higher than controls ((P < 0.0001, P < 0.01, P < 0.05).ConclusionHigh binding of modified DNA with the IgG from RA patient might explain possible antigenic role of 4-OHE2-modified DNA in the production of anti-DNA antibodies. In addition, the induced antibodies have been shown to represent an alternative immunochemical probe to detect oxidative lesions in DNA as well as for the estimation of 8-OHdG levels in different body fluid of RA patients, which may be used as marker in the diagnosis of the disease.

Differentiated mesenchymal stem cells ameliorate cardiovascular complications in diabetic rats

Cardiovascular manifestations are one of the major complications of type 1 diabetes mellitus (T1DM) and supersede the slow progression of DM in most cases as the leading cause of mortality. There have been many studies and trials in regenerating the functional β-cells of islets from mesenchymal stem cells (MSCs) with varied success. The effect of MSCs ex vivo differentiated to mimic functional insulin-secreting β-cells of islets and their impact on restoration of diabetic complications and transplantation via systemic delivery have not been well studied. In the current study, bone marrow MSCs differentiated to insulin-secreting β-cells are used to treat STZ-induced diabetic rats. The post-homing effects of the differentiated MSCs (dMSCs) were endogenous with definite reversal of diabetic parameters. Consequently, the altered cardiac functions like heart beat rate, left ventricular performance, contractility index and physiological body weight gain due to hyperglycemia were amelorated into normacy. The primary onset cardiac perfomance and the endothelial activation were well evidenced by high fibrinogen levels and systolic blood pressure (SBP) being reversed on the treatment by dMSCs. Further high basal [Ca2+]c in isolated endothelial cells and thereby increased ROS confirmed the endothelial activation. The levels of pro-apoptotic makers p53 and Bax were highly expressed in the diabetic groups indicating oxidative stress through ROS induced by high cytosolic calcium skewing the cells towards apoptosis. The expression of the anti-apoptotic marker Bcl-2 was observed to be low in the diabetic group further augmenting the stress state of endothelial cells (ECs) in T1DM. Restoration of [Ca2+]c chelates ROS and the subsequent reversal of pro- and anti-apoptotic markers after the successful treatment of dMSCs proved that endogenous reconstitution of insulin secretion improves diabetic-induced cardiac manifestations.

The underutilization of adjunctive pharmacotherapy in treating acute coronary syndrome patients admitted to a tertiary care hospital in Southwest region, Saudi Arabia

Background: Acute coronary syndrome (ACS) is the most prevalent cardiac disorder. Adjunctive pharmacotherapy has proved to be safe and effective in treating patients with this syndrome. Underutilization of such pharmacotherapy was reported in different studies. Objectives: In this study, we evaluated the underutilization of these pharmacotherapies on patients admitted to Aseer Central Hospital (ACH) with ACS, find out factors that may predict utilization of these therapies, and determine the effect of such pattern of drug utilization on survival at discharge. Materials and Methods: A retrospective cohort of 562 patients admitted with the diagnosis of ACS to ACH during the period from March 2007 to February 2009 was studied. Results: β-blockers (B-blocker) and angiotensin-converting enzyme inhibitors (ACEI) were used in only 69 and 59% of cases, respectively. Aspirin, clopidogrel, and statin were used in 98.4, 82.6, and 89.3% of cases, respectively. The presence of diabetes predicts the use of ACE inhibitors, whereas the diagnosis of unstable angina and ST-elevation myocardial infarction predict the use of statin. Survival rate at discharge was 95.6%. Use of statin and aspirin improved survival. Conclusion: Certain adjunctive pharmacotherapies were underutilized in ACS patients in Southwest region, Saudi Arabia, specifically β-blockers and ACEI. Standard of care should be revised and updated, aiming to improve adherence to guidelines of management of patients with ACS.

Effect of gender difference in management of heart failure patients in aseer, saudi arabia.

Background: Heart failure (HF) is a common medical problem with a high impact on public health. Evidence of gender difference in management of HF is scarce. We conducted a retrospective study to evaluate the presence of gender difference in management of HF patients admitted to the tertiary care hospital in the Aseer region/Saudi Arabia. Patients and Methods: A chart review was conducted at Aseer Central Hospital (ACH) on consecutive patients admitted with the primary diagnosis of HF between Jun 2007 and May 2009. Data were collected on clinical and management profiles and analyzed for the presence of gender difference in HF management. Results: A total of 206 male patients and 94 female patients with HF were reviewed. Ischemic and dilated cardiomyopathy etiologies were significantly higher in male patients (42.7 vs. 28.7%, P < 0.021) and (13.1% vs. 3.2%, P < 0.008), respectively. Renal failure and atrial fibrillation were significantly higher in female patients with HF (20.2 vs., 5.3% P < 0.001) and (20.2 vs. 10.2%, P < 0.018), respectively. Smoking was significantly higher in male patients (11.7 vs. 0%, P < 0.001). Echocardiography was performed equally for both genders and ejection fraction was significantly higher in female patients (38.2 ± 16.9% vs. 30.4 ± 16.6%, P < 0.001). Beta-blockers were prescribed significantly less to female patients (36.2 vs. 57.8%, P < 0.001), while ACE inhibitors and digoxin were prescribed significantly less to male patients (64.1 vs.75.5%, P < 0.049) and (24.8 vs. 36.2%, P < 0.042), respectively. Conclusion: Gender differences were detected in clinical presentation and management of HF. Female patients with HF had less ischemic etiology and smoking, but more atrial fibrillation and renal dysfunction. Female patients were under-treated by Beta-blockers while male patients were under-treated by ACE inhibitors and digoxin. Both genders were investigated equally, and female patients had a better ejection fraction.