Early Diagnosis and Management of Klebsiella Pneumonia Induced Panophthalmitis - A Case Report

Endophthalmitis is an inflammatory condition involving the intraocular cavities, including the Uveal tissue and retina. Panophthalmitis includes the sclera and Tenon’s capsule. Endophthalmitis may be classified as Infective and Sterile endophthalmitis. Infective causes can be further subdivided into Exogenous, Endogenous and Secondary infections from surrounding structures. Exogenous forms arise from perforating injuries or postoperatively. Endogenous endophthalmitis may develop as a result of seeding from a distant focus of infection in the body. Depending on the causative organism, it may be bacterial or fungal.Diabetes mellitus may accentuate the condition. Endophthalmitis can lead to serious complications such as visual loss and Phthisis bulbi. Hence if not managed adequately and early, enucleation may be required.

Structural Mapping of Inhibitors Binding Sites on P-glycoprotein: Mechanism of Inhibition of P-Glycoprotein by Herbal Isoflavones.

Understanding the pattern of inhibitors binding to p-glycoprotein (Pgp). Study Design: Pgp is an ATP dependent transporter protein, responsible for multi-drug resistance in metastatic tumors. It removes toxins by exporting a variety of structurally unrelated compounds outside the cells, which make Pgp a promising target for designing anti cancer supplementary therapeutic molecules. Isoflavones are present in soyabean and other herbal extracts. The idea was to explore inhibitor binding sites on Pgp to find hotspots which eventually may prove useful in designing compounds with higher specificity and affinity. Place and Duration of Study: School of Biotechnology, Gautam Buddha University, Greater Noida, between February 2012 and December 2012. Methodology: The biochemical nature of binding of isoflavones to Pgp has been extensively studied, but the atomic details of their interactions were not understood. Therefore, we have used in silico methods to study binding of eleven isoflavones to Pgp. The docking studies were performed using grid-based ligand docking with energetic (GLIDE). Results: Isoflavones binds at two slightly distinct sites perpendicular to each other, present in the large hydrophobic cavity of Pgp. Three isoflavones bind to site 1, whereas eight isoflavones bind to site 2 by forming van der Waals and H-bonded interactions. Both the sites are highly hydrophobic in nature and are contributed mainly by side chain of non polar residues present on twelve transmembrane -helices. Site 1 has minimum dimension of 7.5Å and maximum as 22Å whereas, site 2 is wider and deeper than site1. One sidewall of the site 2 is formed by polar amino acid residues of helix H12, which makes several hydrogen bonds with ligands. Conclusion: Structure analysis revealed that addition of polar group to hydrophobic ligand may enhance its binding affinity for Pgp, which may be used for designing potent inhibitors to find lead compounds for drug design.

Celecoxib mitigates cigarette smoke induced oxidative stress in mice.

Cigarette smoke (CS) is a rich source of radicals, predisposing the cell to oxidative stress resulting in inflammation. Chronic inflammation is a recognized risk factor for carcinogenesis. Cyclooxygenase-2 (COX-2) is a mediator of inflammatory pathway and may, therefore, contribute to carcinogenesis. There are several reports that suggest the association between CS and COX-2 associated risk to cancer. In the present study, we examined the role of celecoxib (a selective COX-2 inhibitor) in modulating the oxidative stress caused by CS inhalation in mice. CS exposure for a period of 10 weeks caused oxidative stress in the pulmonary and hepatic tissues, as evident from the increase in lipid peroxidation levels (LPO) and decrease in reduced glutathione (GSH) levels. Celecoxib (125 mg/kg body weight for 8 weeks) administration to CS inhaling mice reduced the oxidative stress by decreasing the LPO levels and enhancing the GSH levels in comparison to the CS-exposed group. CS exposure repressed the enzymatic antioxidant defense system, as evident from the decrease in catalase (CAT) and superoxide dismutase (SOD) activities. Co-adminstration of celecoxib considerably reversed the changes in the enzymatic antioxidant defense system. Histopathological studies of lungs showed that CS exposure induced alveolar wall destruction and air space enlargement. In co-treated group, the alveolar septa were thicker than normal with apparent infiltration of inflammatory cells. In CS-exposed group, hepatic tissue exhibited vacuolization and macrophage infiltration. Co-treatment with celecoxib restored the normal histoarchitechture in hepatic tissues of CS inhaling mice. Thus, the present study demonstrated that celecoxib adminstration reduced the oxidative stress-mediated risk to carcinogenesis, due to its ability to boost the antioxidant defense system.

Celecoxib administration exhibits tissue specific effect on 3H-benzo(a)pyrene-DNA adduct formation in cigarette smoke inhaling mice.

In the present study, cigarette smoke (CS) exposure significantly enhanced 3H-B(a)P-DNA adduct formation in both the pulmonary and hepatic tissues. Mice co-treated with CS and celecoxib (a specific COX-2 inhibitor) exhibited a significant decrease in hepatic carcinogen-DNA adduct formation in comparison to the smoke exposed group, however the lungs of the co-treated animals exhibited a significant increase in carcinogen-DNA adduct formation when compared to the control group and smoke exposed group. CS exposure enhanced the activity of carcinogen activation enzymes in both the tissues and decreased the activity of carcinogen detoxification enzymes in the hepatic tissue only, when compared to the control group. Celecoxib administration to CS inhaling mice modulated the carcinogen biotransformation considerably when compared to the CS exposed group. Celecoxib administration to CS inhaling mice produced a low index of carcinogenesis in the hepatic tissue but increased the index of carcinogenesis in the pulmonary tissue. These observations seem to be critical and tissue specific when related to carcinogenesis.