Abrogation of recurrent autoimmunity in the NOD mouse: A critical role for host interleukin 4

BACKGROUND: We previously established a clinically relevant strategy to abrogate recurrent autoimmunity and enable long-term islet graft survival, involving antilymphocyte serum (ALS)-depletion of recipient T cells and intraportal administration of donor pancreatic lymph node cells (PLNCs) along with islet grafts. In this study, we investigated whether Th2 cytokines were required for the tolerizing ability of ALS/PLNC treatment in islet transplantation. METHODS: ALS-treated diabetic NOD recipient mice, and NOD recipient mice deficient in interleukin 4 (IL-4-/-) or 10 (IL-4/10-/-) were transplanted with NOR or NOD.scid islets intraportally along with donor PLNC. Blood glucose levels were monitored to access graft function, sections of graft-bearing livers were histologically examined, and ELISPOT assays were used to assess cytokine profile and frequency of islet-reactive CD4 T cells. RESULTS: We found that ALS/PLNC was not effective in prolonging islet graft survival in diabetic NOD hosts deficient in either IL-4 (NOD.IL-4-/-) or in IL-4 and IL-10 (NOD.IL4-/-/10-/-) (mean survival time, 36 days), contrasting the long-term survival of islet grafts in wild-type NOD mice (mean survival time, > 80 days). In contrast, PLNC deficient in IL-4 promoted long-term graft survival in wild-type NOD hosts similar to that in wild-type PLNC. In wild-type NOD recipients of either wild-type PLNC or IL-4-/- PLNC, the host autoantigen-specific CD4 T cells produced predominately IL-4 coincident with long-term graft survival, whereas, in NOD.IL-4-/- recipients with rejected grafts, the autoreactive T cells produced interferon gamma and low amounts of IL-4. CONCLUSIONS: These data demonstrate that abrogation of recurrent autoimmunity requires host IL-4 and that manipulation of the autoreactive cytokine profile in long-term diabetes may be an effective strategy for islet transplant therapies.     

Color Doppler Visualization of Intramyocardial Coronary Arteries Using a New Echo System: Effect of Contrast Enhancement and Vasodilation

Utilizing a new echocardiographic system, intramyocardial coronary arteries could be demonstrated by color Doppler in a small number of open chest animals. Both intravenous and intracoronary injections of a contrast agent (Levovist) resulted in significant enhancement of color flow signals with an increase in the length, width, and the number of these vessels. Similar results were obtained with intravenous infusion and direct intracoronary injections of a vasodilator (adenosine).     

Correlation between symptoms and external characteristics of cracked teeth: Findings from The National Dental Practice-Based Research Network

Background

Cracked teeth are ubiquitous in the adult dentition. The objective of this study was to determine which patient traits and behaviors and external tooth and crack characteristics correlate with cracked teeth being symptomatic.

Decompensated heart failure: is there a role for the outpatient use of nesiritide?

Heart failure (HF) management has seen enormous advances in the past two decades, including publication of HF management guidelines targeted at further reduction of morbidity and mortality. Nonetheless, the morbidity of HF has steadily increased and now represents one of the largest health care expenditures in this country. Because hospitalization for HF is most likely for patients with more advanced HF, they share a disproportionate burden of the hospitalization costs and will require treatment regimens beyond the current guidelines, if this burden is to be alleviated. In June 2004, a group of investigators who helped establish the natriuretic peptide treatment paradigm, met to discuss the potential role of nesiritide as an outpatient treatment option for patients with symptomatic HF who were at high risk for repeated admissions, a syndrome now described as "chronic decompensated HF." This report presents their considerations on the contribution of natriuretic peptide physiology to the amelioration of progressive left ventricular dysfunction, the therapeutic use of B-type natriuretic peptide, and its potential application to the outpatient management of acute and chronic decompensated HF. The use of outpatient IV nesiritide was considered a promising treatment option for symptomatic chronic decompensated HF patients that merits further investigation. Such an approach, once validated, should be integrated into an evidence-based HF disease management program.     

State of the art: using natriuretic peptide levels in clinical practice

Natriuretic peptide (NP) levels (B-type natriuretic peptide (BNP) and N-terminal proBNP) are now widely used in clinical practice and cardiovascular research throughout the world and have been incorporated into most national and international cardiovascular guidelines for heart failure. The role of NP levels in state-of-the-art clinical practice is evolving rapidly. This paper reviews and highlights ten key messages to clinicians: