Browsing by Author "Wadhwani, Aman"
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Item Open Access Correction to: Mycotic aortic aneurysms post-Intravesical BCG treatment for early-stage bladder carcinoma(2019-12-16) Wadhwani, Aman; Moore, Randy D; Bakshi, Darshan; Mirakhur, AnirudhIn the published article [1] the statement under the subheading ‘Consent for publication’ is incorrect.Item Open Access Intracellular Mechanisms Responsible for Trypsin-induced Increase in Transepithelial Resistance in Intestinal Epithelial Cells(2013-01-25) Wadhwani, Aman; MacNaughton, WallaceApical addition of serine proteases like trypsin to intestinal epithelial cell monolayers causes an increase in transepithelial resistance (RTE); however, the underlying mechanism is unknown. One way that proteases regulate cell function is by cleaving and activating the Protease Activated Receptor (PAR) family of G-proteincoupled receptors. In addition, trypsin has been shown to transactivate the epidermal growth factor receptor (EGFR) via activation of PAR2. Others have shown that activation of EGFR results in increased RTE in epithelial cells. Hence, we hypothesized that trypsin increases RTE by activating PARs and/or transactivating EGFR. Apical addition of trypsin caused a 300% increase in RTE. However, desensitization of PARs-1, 2 and 4 did not significantly affect the trypsin-induced ΔRTE. PD153035 or AG879 caused a significant dose-dependent decrease in trypsin-induced ΔRTE via inhibition of EGFR or ErBb2 tyrosine kinase respectively. Anti-transforming growth factor-α antibody reduced trypsininduced ΔRTE. The trypsin-induced ΔRTE was also reduced by the ERK-1/2 kinase inhibitor or PI3-kinase inhibitor but was not affected by Src-kinase inhibitor. The trypsininduced reduction in flux of FITC-dextran was prevented when cells were pre-treated with PD153035 or AG879. Our data suggest that trypsin increases RTE via transactivation of EGFR and ErbB2 independently of PAR activation. The trypsin induced RTE partially depends upon the activation of MAPK and PI3 kinase but not Src-kinase. Serine proteases may strengthen the epithelial barrier to enhance the efficiency of electrolyte, water and nutrient transport and may represent a method of countering barrier deficiencies associated with intestinal disorders.Item Open Access Mycotic aortic aneurysms post-Intravesical BCG treatment for early-stage bladder carcinoma(2018-08-22) Wadhwani, Aman; Moore, Randy D; Bakshi, Darshan; Mirakhur, AnirudhAbstract Background Intravesicular Bacillus Calmette-Guérin (BCG) is an effective adjunctive therapy for superficial bladder cancer that has been shown to delay recurrence and progression of disease. Serious side effects are relatively rare but are difficult to diagnose and are often overlooked. Vascular complications are particularly rare. Case presentation We report two cases of mycotic aortic aneurysms secondary to BCG treatment, one managed with endovascular stent-graft placement and the other with open surgical repair. The present understanding of disseminated BCGosis, including a literature review, will be discussed. Conclusion The incidence of mycotic aneurysms from BCG treatment is rare and very few cases have been reported in the literature. These cases further expand the current knowledge on vascular complications related to BCG treatment. In the absence of formal guidelines, we recommend a multidisciplinary approach involving vascular surgery, diagnostic and interventional radiology, and infectious disease to manage these patients.