The effect of nizoral and tinidazole on neutrophilic phagocytic activity in patients with rubromycosis and candidiasis

Nisoral and tinidasole effects on Trichophyton rubrum and Candida albicans ability to be destroyed by neutrophils were under study, as were the characteristics of neutrophil phagocytic activity in patients with various forms of trichophytosis and candidiasis over the course of nisoral or tinidasole therapy or combined therapy with both the drugs. Tinidasole and more so nisoral were found to enhance neutrophilic fungicidal activity towards Tr. rubrum and C. albicans. Combined therapy with nisoral and tinidasole distinctly augmented the counts of Ns-RFC and Nc-RFC and increased the values of the phagocytic index and the phagocytic number. Combined administration of the drugs was conducive to elevation of the neutrophilic ability to destroy the fundal elements.     

Up-regulation of cell cycle regulatory genes after renal ischemia/reperfusion: differential expression of p16(INK4a), p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase inhibitor genes depending on reperfusion time

The aim of this study was to evaluate the influence of renal ischemia, cold preservation and reperfusion on the degree of renal kidney senescence. An experimental model of ex vivo renal hemoperfusion was used. Expression of p16(INK4a), p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase inhibitor genes (CDKIGs) was studied immunohistochemically in kidney biopsy samples at baseline and different time points after reperfusion. All three markers were up-regulated in kidney tissue after the reperfusion; however, their activation in different renal cells varied according to the reperfusion time. Expression of p16 was significantly increased in tubular cells at 180 min of reperfusion when compared with the baseline. Activation of p27 was detected in glomerular cells at 15 min and was significantly higher at 60, 120 and 180 min of reperfusion. The marker started increasing in tubular cells at 15 min and was elevated at every time point afterwards. p21 was significantly over-expressed in all renal cells after the reperfusion. It has been shown by the results of the current study that renal ischemia/reperfusion is associated with over-expression of CDKIGs indicating on substantial DNA damage and/or accelerated tissue senescence. For the first time it has been shown that tissue expression of CDKIGs is positively related with the reperfusion time.     

Loss of p27<Superscript>(Kip1) </Superscript>CDKI is a predictor of poor recurrence-free and cancer-specific survival in patients with renal cancer

The importance of cyclin-dependent kinase inhibitors (CDKI) in benign and malignant urological diseases is a subject of intense ongoing investigation. The goal of the current study was to analyze the expression of p27^(Kip1) CDKI in benign and malignant renal cells and assess their possible association with different clinical parameters. Expression of p27^(Kip1) was evaluated and compared in 24 normal human kidneys and in 52 renal cell carcinoma (RCC) tissue samples. Intensity of the expression was compared between the groups and association was analyzed with cancer clinical parameters. The expression of the marker was significantly higher in normal than in RCC samples (P = 0.0045). Intensity of p27^(Kip1) expression in RCC was negatively correlated with tumor size (Rho = −0.438, P = 0.0051) and associated with pathological stage and grade (P = 0.0488 and < 0.0001, respectively). The patients with symptomatic disease had significantly less marker expression than incidentally discovered tumors (P = 0.0301). Loss of p27^(Kip1) expression, pathological stage, grade and tumor size were the risk-factors for disease recurrence (P = 0.0072, 0.0011, 0.0467 and < 0.0001, respectively) and patient survival (P = 0.0021, 0.0106, 0.0151 and 0.0021, respectively). With Cox multivariate analysis loss of p27^(Kip1) expression (hazard ratio 9.3, P = 0.002) and tumor size (hazard ratio 5.9, P = 0.015) were the predictors of cancer-specific survival. Expression of p27^(Kip1) is significantly decreased in RCC as compared with normal kidney tissue. Intensity of the expression is associated with clinical parameters: tumor size, stage, grade and disease presentation. Loss of p27^(Kip1) expression is a risk-factor for disease recurrence and the strongest predictor of cancer-specific survival.     

Effects of intrarenal administration of the calcium antagonist nimodipine during porcine aortic occlusion-induced ischemia/reperfusion injury

Ca++ antagonists have been tested to improve I/R injury in the kidney, but their clinical use is limited due to their hypotensive properties. Therefore, we tested the hypothesis on whether infusing the Ca++ blocker nimodipine directly into the renal artery would reduce kidney cell apoptosis and thus improve organ function in a porcine model of suprarenal abdominal aortic cross-clamping. In a prospective, randomized, controlled, blinded study, anesthetized, mechanically ventilated, and instrumented pigs underwent 45 min of suprarenal aortic cross-clamping animals receiving either 0.25 microg kg(-1) min(-1) nimodipine (n = 8) or vehicle (n = 8). Systemic and right kidney hemodynamics, oxygen exchange, and metabolism were assessed before clamping, as well as before and at 75 and 195 min of reperfusion (i.e., at 120 and 240 min after aortic occlusion). At the end of the experiments, the right kidney was harvested for conventional hematoxylineosin staining and immunohistochemistry for the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) gene expression and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin end labeling test). Neither systemic nor renal hemodynamics and oxygen exchange, plasma and urine protein concentrations, urine osmolarity, and lactate-pyruvate ratios showed any intergroup difference. Nimodipine infusion resulted in a significantly higher creatinine clearance after 195 min of reperfusion (26 [17 - 42] vs. 17 [9 - 22] mL x min(-1)) and attenuated renal tubular damage, as indicated by lower urinary small protein (25 kd) concentrations. Improved renal function was concomitant with significantly less pronounced positive nuclear terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin end labeling staining. In a porcine model of suprarenal aortic cross-clamping, intrarenal nimodipine infusion improved postischemia kidney function, most likely as a result of attenuated glomerular apoptosis.     

Expression of p27<Superscript>(Kip1)</Superscript>, cyclin D3 and Ki67 in BPH,prostate cancer and hormone-treated prostate cancer cells

p27^(Kip1), cyclin D3 and Ki67 are the markers of DNA damage and cell proliferation. The goal of the current study was to analyze expression of the markers in benign and malignant prostate cancer tissues. Activity of p27^(Kip1), cyclin D3 and Ki67 was immunohistochemically evaluated in different cells of BPH, prostate cancer (PCa) and hormonally treated prostate cancer (HTPCa) tissues. The tissue samples were derived by means of TURP or radical prostatectomy. Intensity of the expression was compared between the groups, and association was sought with clinical parameters. Total expression of p27^(Kip1) was significantly higher in BPH as compared with PCa. Epithelial marker expression was higher in HTPCa than in PCa. Intensity of the expression in epithelial, vascular and ductal cells was negatively associated with the tumor stage and Gleason grades. Total Ki67 activity was positively correlated with patient age and serum PSA level. There was significantly higher expression in PCa and hormone-escaped PCa (HEPCa) as compared with BPH. Epithelial and vascular marker expression was positively associated with tumor stage and Gleason grades. There was a positive correlation between cyclin D3 and serum PSA level. With the increase of Gleason grades, cyclin D3 expression increased significantly. Expression of p27^(Kip1) negatively correlated with Ki67 and cyclin D3, while the latter two markers correlated positively. p27^(Kip1) is down-regulated, whereas Ki67 and cyclin D3 are up-regulated in PCa. Intensity of the markers’ expression is associated with tumor stage and grades. Hormonotherapy of PCa causes activation of p27^(Kip1). HEPCa is characterized by increased Ki67 expression.