Cyclooxygenase-2 Expression Increases with the Stage and Grade in Transitional Cell Carcinoma of the Urinary Bladder

Objectives: Experimental models of carcinogenesis show that non-steroidal anti-inflammatory drugs (NSAIDs) increase apoptosis, inhibit angiogenesis and reduce metastases. A linkage between the activity of prostaglandin synthase enzyme cyclooxygenase-2 (COX-2), a known mediator of inflammation, and cancer angiogenesis is implicated. We investigated the expression of COX-2 in bladder cancer tissue specimens using immunohistochemistry. Methods: The immunohistochemical expression of COX-2 in bladder cancer was evaluated by scoring the intensity of immunoreactivity from 0 to 3. Further, the degree of COX-2 expression was correlated with the tumor grade and depth of invasion (T stage). Result: Fifty eight percent patients (n=22) had superficial bladder tumors, while 42% (n=16) were invasive bladder cancers. Overall, COX-2 immuno-positivity was seen in 84.2% (32/38) patients. COX-2 expression was positive in 76.4% (13/17) cases with pTa tumors, 100% (5/5) of pT1 tumors, 86.6% (13/15) of pT2 tumors and in 100% (1/1) of pT3 tumor. The higher stage tumors stained more intensely; this correlation wassignificant(p=0.01987; χ2=19.6977). With reference to the grade of tumors, a positive expression was seen in 81.25% (13/16) of the low-grade tumors and 89% (17/19) of the high-grade tumors. The differential COX-2 expression relative to the grade of tumor was found to be statistically significant (p=0.05; χ2=15.8612). Conclusion: The degree of COX-2 expression is significantly increased with advancing grade and T stage of disease (p < 0.05).     

Experience with similar biologic rituximab in 77 patients of granulomatosis with polyangiitis—a real-life experience

Clinical Rheumatology - To present single centre experience on the efficacy and safety of similar biologic of rituximab in patients with granulomatosis with polyangiitis (GPA). This was a...     

Contribution of free radicals to Pseudomonas aeruginosa induced acute pyelonephritis

Pyelonephritis induces an inflammatory process in the renal parenchyma, which may occur as a result of excessive reactive nitrogen intermediates (RNI) and reactive oxygen species (ROS) and/or impaired antioxidant capacity. In the present investigation, contribution of free radicals to the development of acute pyelonephritis induced by planktonic and biofilm cells of Pseudomonas aeruginosa was studied. Increase in production of RNI and ROS in urine, bladder and renal tissue following infection with P. aeruginosa was observed which correlated with bacterial load, neutrophil recruitment and malondialdehyde (MDA). Evaluation of the data revealed that excessive production of free radicals causes tissue damage leading to bacterial persistence in host's tissues. Treatment of mice with N-acetylcysteine (NAC), a potent antioxidant, lead to significant amelioration of oxidative stress and subsequent decrease in bacterial titer, neutrophil influx, MDA as well as tissue pathology highlighting important role of free radicals in P. aeruginosa induced pyelonephritis. Results of the present study bring out that production of RNI and ROS contributes to the pathophysiology of pyelonephritis. These findings may be relevant for the better understanding of host–parasite interactions and may be of clinical importance in the development of preventive intervention against P. aeruginosa induced pyelonephritis.     

Posterior reversible encephalopathy syndrome in a patient with hepatitis B induced type 1 membranoproliferative glomerulonephritis

Posterior reversible encephalopathy syndrome (PRES) is a rare complication of nephrotic syndrome and corticosteroid therapy. Here, we discuss an 18 year old man with type 1 membranoproliferative glomerulonephritis (MPGN) secondary to hepatitis B infection who developed posterior leukoencephalopathy while on therapy with lamivudine and prednisone. He developed seizures and vision loss. He also had hypertension, but no sudden elevation was recorded at any time. Magnetic resonance imaging revealed patchy areas of altered signal intensity involving cortical gray and subcortical white matter in the bilateral frontoparietal regions, occipital cortices, temporal cortices and cerebellar hemispheres, and hyperintensity on T2W and FLAIR sequences. Tapering of prednisone and controlling hypertension resulted in clinical improvement within a few days, and in a month MRI was normal. Diagnosing PRES requires a high index of suspicion when treating similarly susceptible patients. PRES as a complication during the treatment of MPGN secondary to hepatitis B has, to our knowledge, never been reported previously in the literature.     

Extracellular Laccase from a Newly Isolated Psychrotolerant Strain of <Emphasis Type="Italic">Cladosporium</Emphasis> <Emphasis Type="Italic">tenuissimum</Emphasis> (NFCCI 2608)

A newly isolated psychrotolerant fungus from cold desert in Indian Himalaya has been investigated for laccase production. Based on phenotypic and genotypic characters, the fungus has been identified as Cladosporiumtenuissimum. The fungus could grow between 4 and 30 °C (optimum 24 °C). In ABTS plate assays, the efficiency for enzyme production was relatively higher at low temperature. In quantitative estimations, the laccase activity was recorded almost twice (15.10 ± 0.78 UL^?1) at 14 °C in comparison to the activity (8.05 ± 0.94 UL^?1) at 24 °C. Optimum pH for fungal growth as well as laccase production was 5.5. The molecular mass of laccase determined by native PAGE was approximately 48 kDa. Km and Vmax values of the enzyme were determined as 0.21 mM and 0.38 mM min^?1, respectively. Addition of carbon and nitrogen sources and organic solvents (supplements) affected enzyme activity significantly; ethanol being the best enhancer.     

Lysosomal leakage and lack of adaptation of hepatoprotective enzyme contribute to enhanced susceptibility to ethanol-induced liver injury in female rats

BACKGROUND: Women exhibit greater liver damage than men after chronic alcohol consumption. Similar findings are reported in animal models. Here, we determined whether differential liver injury occurred in male and female rats after feeding these animals liquid diets containing either ethanol or isocaloric dextrose with fish oil as the sole source of lipid. METHODS: Control and ethanol liquid diets containing fish oil were pair-fed to male and female rats for 8 weeks. Liver damage was evaluated by triglyceride accumulation, lipid peroxide formation, serum transaminases, histological evaluation, and the activities of selected lysosomal and hepatoprotective enzymes. RESULTS: Fatty liver was detected after ethanol feeding in both genders, but in female rats, triglyceride levels were 60% higher, lipid peroxides were 2-fold higher, and inflammatory cells were more evident than in males. A 2-fold elevation of cathepsin B in hepatic cytosol fractions, indicating lysosomal leakage, was detected in ethanol-fed female rats but no such elevation was observed in males. The basal activity of the hepatoprotective enzyme, betaine-homocysteine methyltransferase was 4-fold higher in livers of control male rats than females, and the enzyme activity was further elevated in ethanol-fed male rats but not in females. CONCLUSIONS: Thus, female rats given ethanol in a diet containing fish oil exhibited more severe liver damage than males. We propose that this difference results, in part, from a greater tendency by females to accumulate hepatic fat, thereby enhancing the potential for oxidative stress, which in turn leads to hepatic inflammation. In addition, our findings indicate that female rats have a higher susceptibility to liver damage because of a reduced capacity for hepatoprotection.     

The changing landscape of interventional cardiology: A survival guide in the era of health system consolidation

Practice environments for interventional cardiologists have evolved dramatically and now include small independent practices, large cardiology groups, multispecialty groups, and large integrated health systems. Increasingly, cardiologists are employed by hospitals or health systems. Data from MedAxiom and the American College of Cardiology (ACC) demonstrate an exponential increase in the percentage of cardiologists in employed positions from 10% in 2009 to 87% in 2020. This white paper explores these profound changes, considers their impact on interventional cardiologists, and offers guidance on how interventional cardiologists can best navigate this challenging environment. Finally, the paper offers a potential model to improve the employed physician experience through greater physician involvement in decision making, which may increase jobs satisfaction.