Effects of angiotensin converting enzyme inhibitors, peroxisome and gamma agonists, and statins on a rat model proliferators activated receptor - of hypertension

Hypertension is a common and complex human disease that causes significant morbidity and mortality worldwide. The role of endothelial dysfunction as an early event of pathophysiologic importance has been recently delineated. Nitric oxide [NO] is an important vasodilator and a potent regulator of inflammation, and mitogenesis. Therefore, inhibition of NO synthesis provided an interesting model of hypertension with specific cardiovascular alterations in which different events of the disease process could be traced. The aim of this work was to study the cardiovascular abnormalities in a rat model of hypertension induced by administration of the NO synthase inhibitor, N?-nitro-L-arginine methyl ester [L-NAME]. In addition, the effects of short and long term administration of an angiotensin converting enzyme inhibitor [Lisinopril], a peroxisome proliferators activated receptor [PPAR]-? agonist [Fenofibrate], a PPAR- gamma agonist [Pioglitazone] and a statin [Atorvastatin] were studied. The study was conducted on 128 rats divided into groups and received the studied drugs. Arterial blood pressure and TGF- beta 1 were recorded. The animals were then sacrificed and the heart weight/body weight [HW/BW] ratio was calculated. Routinely processed hearts and aortae were examined to assess degree of inflammation or fibrosis. This was followed by immunohistochemical detection of CD68 and PCNA and histochemical staining using Masson trichrome stain. Evaluation was done by computerized image analysis. Short term administration of L-NAME was associated with a significant increase in blood pressure associated with marked myocardial inflammatory response [mostly CD68 positives macrophages] and increased proliferative activity. Long term administration of L-NAME resulted in a significant aggravation of hypertension accompanied by myocardial hypertrophy and significant increase in HW/BW ratio. Extensive fibrosis and a significant increase in plasma TGF- beta 1 level were noted. Short term administration of the studied drugs showed that only Lisinopril showed a significant decrease in blood pressure. The inflammatory and proliferative changes were attenuated by short term administration of the studied drugs, yet with different degrees. Long term administration of all drugs except Fenofibrate led to a significant reduction of blood pressure, HW/BW ratio, fibrosis and plasma TGF- beta 1. Disturbances of NO production are likely to be major determinants of endothelial dysfunction, hypertension and their pathological consequences; hence, directing therapy towards conserving endothelial NO bioavailability seems to be of paramount importance. The tested drugs were capable of modulating the different aspects of the disease whether the early or late changes, though their profiles were different. Among the studied classes of drugs, Lisinopril was superior in modulating alterations associated with hypertension

Study of serum and urinary vascular cell adhesion molecule-1 in patients with lupus nephritis

Systemic lupus erythenwtosus [SLE] is a chronic multisystem autoimmune disease. Renal involvement [lupus nephritis; LN] is a frequent and potentially serious complication that worsens morbidity and mortality. LN is a chronic disease with remissions and relapses, and this is important to predict aiming for optimal management. However, a consistent approach still has not been adopted. To study serum and urinary' soluble vascular cell adhesion molecule-I [sVCAM-1] levels in patients with lupus nephr itis and their correlation with the disease activity, laboratory data and renal pathology. Twenty three patients with lupus nephritis and twenty age, sex and ethnic matched healthy controls were subjected to physical examination, abdominal ultrasound, laboratory investigations including: Complete blood cell count, eiythrocyte sedimentation rate [ESR], renal functions, urine analysis, 24-hour urinary protein excretion, liver functions, serum antinuclear antibody [ANA], anti-double stranded deoxyribonucleic acid [anti-dsDNA], serum and urinaly soluble VCAM-1 [sVCAM-1] and other necessary investigations. Percutaneous renal biopsy, with histopathological assessment and determination of activity and chronicity indices, was done for all patients. LN patients had a statistically sign[ficantly higher serum [S] and urinary sVCAM-1, S. ANA, S. antidsDNA, ESR, blood urea, S.creatinine, S.uric acid, 24-hour urinary protein excretion and S. alanine and aspartate aminotransferases, and a statistically significantly lower hemoglobin concentration, S. albumin and creatinine clearance tjian healthy controls. Renal biopsy assessment showed World Health Organization [WHO] class 11 LN in 3 patients, class iii in 4 patients, class IV in 13 patients and class V in 3 patients. S. sVCAM-1 was statistically significantly higher in classes III, IV and V LN than controls and in class IV LN than class II. Urinary sVCAM-1 was statistically signficantly higher in classes II, III, IV and V LN than controls and in classes III and IV LN than class II. Anti-dsDNA was statistically significantly higher in classes III and IV LN than controls, with no statistically significant differences in between the WHO classes. S. and urinary sVCAM-1 showed a statistically wreianon with the total SLEDAI score, pathologic activity index and urinary protein excretion, with a significantly positive correlation between S. and urinary sVCAM-1. A significantly negative correlation was present between S. sVCAM-1 and hemoglobin concentration, and between urinary sVCAM-1 and S. albumin. As regards anti-dsDNA, no statistically significant correlations were observed. In patients with LN, serum and urinary sVCAM-1 are positively correlated with the total SLEDAI score, pathologic activity index and urinary protein excretion. Measurement of their levels, specially urinary sVCAM-1, seems to be valuable in evaluating LNpatients. Further studies are recommended to assess the role of repeated measurements. Whether a blockade of soluble VCAM-1 could have a therapeutic implication in LN remains to be investigated

Detection of cyclooxygenase-2 [COX-2] expression in non-small cell lung carcinoma. An immunohistochemical and computerized image analysis study

Lung cancer is the leading cause of cancer death all over the world. Evidence is accumulating to suggest that cyclooxygenase-2 [COX-2] is involved the pathogenesis and progression of some types of lung cancer. COX-2 is one of the novel targets under evaluation for non-small cell lung carcinoma [NSCLC] therapy and chemoprevention. The aim of the present study was to detect COX-2 expression in non-small cell lung carcinoma [NSCLC] and to determine its correlation with various clinic pathological parameters. The expression of COX-2 was assessed in 30 patients with NSCLC using immunohistochemistry, followed by quantitative assessment of the immunostaining using computerized image analysis. The present work was conducted on 30 patients with NSCLC: squamous cell carcinoma [15 patients], adenocarcinoma [10 patients], and undifferentiated large cell carcinoma [5 patients]. Overall, 70% of studied NSCLC expressed COX-2. 60% of squamous cell carcinoma [SCC], 80% of adenocarcinoma [ADC] and 80% of undifferentiated large cell carcinoma [ULCC] showed positive immunostaining for COX-2. No significant correlation was found between tumor histological type and each of frequency and degree of COX-2 expression [p=0.569 and p=0.094 respectively]. Though the expression of COX-2 increased with tumor grade, the relation between COX2 expression [both the frequency and degree of expression] and tumor grade was not significant [p=0.778 and p=0.247 respectively for SCC, and p=0.641 and p=0.067 respectively for ADC]. A statistically significant difference was found between node positive and node negative cases as regards the degree of COX2 expression [p=0.05]. No significant relationship was found between COX-2 expression and age and sex of patients, smoking and tumor stage. COX-2 is frequently overexpressed in NSCLC especially in adenocarcinoma and undifferentiated large cell carcinoma. Expression was higher in node-positive tumors and tended to increase with tumor grade, suggesting that COX-2 might play a role in the pathogenesis and/or progression of these tumors. COX-2 appears to be a potentially promising target for therapy and chemoprevention of NSCLC