Streptozotocin (STZ)-induced diabetes mellitus (DM) offers a very cost effective and expeditious technique that can be used in most strains of rodents, opening the field of DM research to an array of genotypic and phenotypic options that would otherwise be inaccessible. Despite widespread use of STZ in small animal models, the data available concerning drug preparation, dosing and administration, time to onset and severity of DM, and any resulting moribundity and mortality are often limited and inconsistent. Because of this, investigators inexperienced with STZ-induced diabetes may find it difficult to precisely design new studies with this potentially toxic chemical and account for the severity of DM it is capable of inducing. Until a better option becomes available, attempts need to be made to address shortcomings with current STZ-induced DM models. In this paper we review the literature and provide data from our pancreatic islet transplantation experiments using single high dose STZ-induced DM in NCr Athymic Nude mice with hopes of providing clarification for study design, suggesting refinements to the process, and developing a more humane process of chemical diabetes induction.

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Immunosuppression is a known risk factor for B-cell non-Hodgkin lymphoma (NHL), yet mechanisms of tumor-associated immunosuppression remain to be fully characterized. We examined the immunophenotype of 40 NHL patients and 27 age-matched healthy volunteers to better understand systemic immune suppression. NHL peripheral blood mononuclear cells had significantly decreased interferon-␥ production and proliferation. This suppression was not the result of regulatory T cells, interleukin-6 or interleukin-10, as these factors were not different between NHL and healthy volunteers (controls). We were able to restore T-cell proliferation by removing NHL monocytes, suggesting that these monocytes are suppressive. This suppression was mediated in part through arginine metabolism as exogenous arginine supplementation partially overcame monocytes' suppression of T-cell proliferation in vitro and NHL patients had elevated arginase I in their plasma. NHL monocytes had impaired STAT1 phosphorylation and interferon-␣ production to CpG stimulation and a dendritic cell differentia- IntroductionSystemic immune suppression is often seen in cancer patients and is thought to contribute to patient morbidity via tumor-mediated immune evasion. Indeed, patients with compromised immune systems, such as those with HIV infection, or on immunosuppressive medications are at increased risk of developing non-Hodgkin lymphoma (NHL). 1,2 Polymorphisms in host germline immune genes also have been associated with risk of developing NHL 3 as well as survival in NHL patients. 4 Conversely, a small percentage of patients with indolent NHL have spontaneous regression of their disease without any treatment, 5 possibly linked to a host antitumor immune response. The presence of host immune cells in the tumor microenvironment has also been correlated with treatment outcome and survival. [6][7][8][9] Of note, reduction in absolute count of circulating lymphocytes has been identified as a poor prognostic factor for overall survival in newly diagnosed NHL 10,11 as well as a predictor of poor treatment response. 9,12,13 Although evidence for the role of immune suppression in tumor establishment and pathogenesis is unquestionable, the mechanisms and the cellular phenotype of systemic immune suppression in NHL patients remain to be fully characterized.In this study, we investigated the qualitative and quantitative systemic immune suppression in B-cell NHL. We found circulating mononuclear cells had suppressed interferon-␥ (IFN-␥) recall response and proliferative capacity. These suppressed functions were mediated by circulating monocytes and partly mediated via arginine metabolism. These monocytes also had other impaired adaptive immune response including a decreased capacity to generate mature dendritic cells. In addition, the innate immune response of these monocytes to CpG stimulation was impaired as measured by intracellular STAT1 phosphorylation and interferonalpha (IFN-␣) production. These multifactorial suppressive functions of monocytes in NHL were corre...

Advances in percutaneous coronary intervention (PCI) during the past decade have led to more widespread use of these procedures in older and sicker patients. Refinement of periprocedural antithrombotic therapy has played a particularly important role in reducing ischemic complications to very low levels in routine practice. Although the use of more powerful antiplatelet agents has been associated with increased risk of bleeding (especially among the elderly and patients with serious comorbidities), such complications have traditionally been viewed as benign in nature. Recent studies, however, have identified major bleeding after PCI as an important predictor of increased mortality. Whether this relationship between bleeding and risk of death is cause-and-effect, or merely an association based on shared risk factors, remains unclear. In this review, we examine the basis for a possible causal link between post-PCI bleeding and subsequent mortality. Possible mechanisms underpinning such a link are discussed, including a potential adverse role for blood transfusion in this setting. A framework for further clinical evaluation of this issue is presented.