Sodium hypochlorite (NaOCl) is the active ingredient in household bleach and is a very common chemical. It has been used in medical and commercial situations dating back to the 18th century for its disinfectant properties, including topical use in medicine as an antiseptic. For this indication, NaOCl is a proven and safe chemical. However, exposure of NaOCl beyond topical use, whether it is intentional or accidental, is associated with significant risks due to its strong oxidizing properties. Potentially damaging scenarios include ingestion, inhalation, deposition into tissue or injection into the bloodstream. All of these scenarios can lead to significant morbidity and even mortality. In this review, we examine the toxicity associated with NaOCl exposure and analyze potential mechanisms of injury, placing special emphasis on the potential for renal toxicity. Due to the extreme ease of access to household bleach products and its use in medicine, it is important for the clinician to understand the potential damage that can occur in NaOCl exposures so that complications can be prevented before they arise.

Dysregulation of β-catenin levels and localization and constitutive activation of β-catenin/TCF (T cell factor)-regulated gene expression occur in many cancers, including the majority of colorectal carcinomas and a subset of ovarian endometrioid adenocarcinomas. Based on the results of microarray-based gene expression profiling we found the insulin receptor substrate 1 (IRS1) gene as one of the most highly up-regulated genes upon ectopic expression of a mutant, constitutively active form of β-catenin in the rat kidney epithelial cell line RK3E. We demonstrate expression of IRS1 can be directly activated by β-catenin, likely in part via β-catenin/TCF binding to TCF consensus binding elements located in the first intron and downstream of the IRS1 transcriptional start site. Consistent with the proposal that β-catenin is an important regulator of IRS1 expression in vivo, we observed that IRS1 is highly expressed in many cancers with constitutive stabilization of β-catenin, such as colorectal carcinomas and ovarian endometrioid adenocarcinomas. Using a short hairpin RNA approach to abrogate IRS1 expression and function, we found that IRS1 function is required for efficient de novo neoplastic transformation by β-catenin in RK3E cells. Our findings add to the growing body of data implicating IRS1 as a critical signaling component in cancer development and progression.

Cancer cells can live and grow if they succeed in creating a favorable niche that often includes elements from the immune system. While T lymphocytes play an important role in the host response to tumor growth, the mechanism of their trafficking to the tumor remains poorly understood. We show here that T lymphocytes consistently infiltrate the primary brain cancer, medulloblastoma. We demonstrate, both in vitro and in vivo, that these T lymphocytes are attracted to tumor deposits only after the tumor cells have interacted with tumor vascular endothelium. Macrophage Migration Inhibitory Factor (MIF)” is the key chemokine molecule secreted by tumor cells which induces the tumor vascular endothelial cells to secrete the potent T lymphocyte attractant “Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES).” This in turn creates a chemotactic gradient for RANTES-receptor bearing T lymphocytes. Manipulation of this pathway could have important therapeutic implications.

A dissatisfaction with obesity-related comorbidities, most notably hypertension and urinary incontinence, was a motivating factor in choosing to undergo bariatric surgery. Patients expected improvement in their comorbid illnesses; however, they still possessed unrealistic weight loss expectations for their intended weight loss procedure.