Catastrophic gastrointestinal injury due to battery acid ingestion.

BACKGROUND: Acids account for 20% of all chemical exposures through various routes. Caustic acids such as hydrochloric and sulfuric acid are common ingredients in many household and industrial products. Due to the corrosive properties of these substances, tissue injury caused by oral exposure can lead to severe esophageal and gastrointestinal burns. CASE REPORT: We report a case of a patient presenting with severe acidosis, who required multiple laparoscopic evaluations to assess various gastrointestinal tract injuries and who ultimately underwent total gastrectomy. The diagnosis was made primarily based on the arterial blood gas and esophagogastroduodenoscopy findings, as well as the pathological examinations of various biopsied and resected tissues showing hemorrhagic necrosis of the esophagus, stomach, and small bowel. This patient eventually admitted to having ingested an unspecified amount of battery acid. CONCLUSIONS: Collaborative efforts by Emergency Medicine, Pathology, and General Surgery services are required for timely diagnosis, treatment, and management of patients after caustic acid exposures.

A novel multimeric form of FasL modulates the ability of diabetogenic T cells to mediate type 1 diabetes in an adoptive transfer model.

Activation induced cell death (AICD) via Fas/FasL is the primary homeostatic molecular mechanism employed by the immune system to control activated T-cell responses and promote tolerance to self-antigens. We herein investigated the ability of a novel multimeric form of FasL chimeric with streptavidin (SA-FasL) having potent apoptotic activity to induce apoptosis in diabetogenic T cells and modulate insulin-dependent type 1 diabetes (IDDM) in an adoptive transfer model. Diabetogenic splenocytes from NOD/Lt females were co-cultured in vitro with SA-FasL, SA control protein, or alone without protein, and adoptively transferred into NOD/Lt-Rag1(null) recipients for diabetes development. All animals receiving control (Alone: n=16 or SA: n=17) cells developed diabetes on average by 6 weeks, whereas animals receiving SA-FasL-treated (n=25) cells exhibited significantly delayed progression (p<.001) and decreased incidence (70%). This effect was associated with an increase in CD4(+)CD25(+) T cells and correlated with FoxP3 expression in pancreatic lymph nodes. Extracorporeal treatment of peripheral blood lymphocytes using SA-FasL during disease onset represents a novel approach that may alter the ability of pathogenic T cells to mediate diabetes and have therapeutic utility in clinical management of IDDM.

Ex vivo expansion of CD4+CD25+FoxP3+ T regulatory cells based on synergy between IL-2 and 4-1BB signaling.

Naturally occurring CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells require three distinct signals transduced via TCR, CD28, and IL-2R for their development and maintenance. These requirements served as the basis for several recently developed ex vivo expansion protocols that relied on the use of solid support-bound Abs to CD3 and CD28 in the presence of high dose IL-2. We report in this study that Treg cells up-regulate the expression of inducible costimulatory receptor 4-1BB in response to IL-2, and stimulation using this receptor via a novel form of 4-1BB ligand (4-1BBL) fused to a modified form of core streptavidin (SA-4-1BBL) was effective in expanding these cells up to 110-fold within 3 wk. Expanded cells up-regulated CD25, 4-1BB, and membranous TGF-beta, suppressed T cell proliferation, and prevented the rejection of allogeneic islets upon adoptive transfer into graft recipients. Importantly, SA-4-1BBL rendered CD4(+)CD25(-) T effector cells refractive to suppression by Treg cells. This dual function of signaling via 4-1BB, vis-à-vis Treg cell expansion and licensing T effector cells resistant to Treg cell suppression, as well as the up-regulation of 4-1BB by IL-2 may serve as important regulatory mechanisms for immune homeostasis following antigenic challenge. Stimulation using a soluble form of SA-4-1BBL represents a novel approach to expand Treg cells with potential therapeutic applications in autoimmunity and transplantation.

Prophylactic fenbendazole therapy does not affect the incidence and onset of type 1 diabetes in non-obese diabetic mice.

Fenbendazole (FBZ) is a common, highly efficacious broad-spectrum anthelmintic drug used to treat and limit rodent pinworm infections. However, the effect of its prophylactic use on the immune response of rodents is largely undefined. The non-obese diabetic (NOD) mouse is a model commonly used to study type 1 diabetes (T1D). Parasitic infections will inhibit diabetes development in NOD mice; thus, in the presence of contamination, prophylactic treatment with anthelmintics must be considered to maintain experimental research. Herein, we investigated the prophylactic use of FBZ in NOD mice to determine its effect on the incidence and onset of diabetes, lymphocyte sub-populations and T cell proliferative responses. NOD mice were separated into control and treatment groups. The treatment group received a diet containing FBZ. Animals were monitored for the incidence and onset of T1D. At matched time points, diabetic and non-diabetic mice were killed and splenic lymphocytes analyzed for various cell sub-populations and mitogen-induced proliferative responses using flow cytometry. Treated and control mice were monitored >23 weeks with no detectable effects on the incidence or onset of diabetes. Moreover, no significant differences were detected in lymphocyte sub-populations and mitogen-induced CD4(+) and CD8(+) proliferative responses between control and treatment groups. These results suggest that prophylactic FBZ treatment does not significantly alter the incidence or onset of diabetes in NOD mice. The prophylactic use of FBZ, therefore, presents a viable approach for the prevention of pinworm infection in precious experimental animals with substantial scientific and economic benefits.