University of Medicine and Dentistry of New Jersey

About: University of Medicine and Dentistry of New Jersey is a based out in . It is known for research contribution in the topics: Population & Poison control. The organization has 14634 authors who have published 19610 publications receiving 1041794 citations.

Adenosine promotes alternative macrophage activation via A2A and A2B receptors

Abstract: Adenosine has been implicated in suppressing the proinflammatory responses of classically activated macrophages induced by Th1 cytokines. Alternative macrophage activation is induced by the Th2 cytokines interleukin (IL)-4 and IL-13; however, the role of adenosine in governing alternative macrophage activation is unknown. We show here that adenosine treatment of IL-4- or IL-13-activated macrophages augments the expression of alternative macrophage markers arginase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and macrophage galactose-type C-type lectin-1. The stimulatory effect of adenosine required primarily A2B receptors because the nonselective adenosine receptor agonist 5′-N-ethylcarboxamidoadenosine (NECA) increased both arginase activity (EC50=261.8 nM) and TIMP-1 production (EC50=80.67 nM), and both pharmacologic and genetic blockade of A2B receptors prevented the effect of NECA. A2A receptors also contributed to the adenosine augmentation of IL-4-induced TIMP-1 release, as both adenosine and NECA were less efficacious in augmenting TIMP-1 release by A2A receptor-deficient than control macrophages. Of the transcription factors known to drive alternative macrophage activation, CCAAT-enhancer-binding protein β was required, while cAMP response element-binding protein and signal transducer and activator of transcription 6 were dispensable in mediating the effect of adenosine. We propose that adenosine receptor activation suppresses inflammation and promotes tissue restitution, in part, by promoting alternative macrophage activation.—Csoka, B., Selmeczy, Z., Koscso, B., Nemeth, Z. H., Pacher, P., Murray, P. J., Kepka-Lenhart, D., Morris S. M., Jr., Gause, W. C., Leibovich, S. J., Hasko, G. Adenosine promotes alternative macrophage activation via A2A and A2B receptors.

Is Prehypertension a Risk Factor for Cardiovascular Diseases

Abstract: Background and Purpose— The Joint National Committee on High Blood Pressure identified a new category of blood pressure in adults termed prehypertension. Our objective was to determine the long-term risk of cardiovascular diseases associated with this new category in a well-defined cohort of adults. Methods— We evaluated the association of prehypertension (120 to 139/80 to 89 mm Hg) and hypertension (>140/90 mm Hg) with the incidence of atherothrombotic brain infarction (ABI), all strokes, myocardial infarction (MI), and coronary artery disease (CAD) using pooled repeated measures and Cox proportional hazards analyses during follow-up after adjusting for age, gender, obesity, diabetes mellitus, hypercholesterolemia, cigarette smoking, and study period in a cohort of 5181 persons who participated in the Framingham Study. Results— Among the 11 116 person observations with a mean follow-up period of 9.9±1.0 years, prehypertension was not associated with an increased risk for ABI (relative risk [RR], 2.2; 95%...

Induction of neuronal apoptosis by camptothecin, an inhibitor of DNA topoisomerase-I: evidence for cell cycle-independent toxicity.

Abstract: Camptothecin is an S-phase-specific anticancer agent that inhibits the activity of the enzyme DNA topoisomerase-I (topo-I). Irreversible DNA double-strand breaks are produced during DNA synthesis in the presence of camptothecin, suggesting that this agent should not be toxic to nondividing cells, such as neurons. Unexpectedly, camptothecin induced significant, dose-dependent cell death of postmitotic rat cortical neurons in vitro; astrocytes were more resistant. Aphidicolin, an inhibitor of DNA polymerase alpha, did not prevent camptothecin-induced neuronal death, while death was prevented by actinomycin D and 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole as well as cycloheximide and anisomycin, inhibitors of RNA and protein synthesis, respectively. Camptothecin-induced neuronal death was apoptotic, as characterized by chromatin condensation, cytoplasmic shrinking, plasma membrane blebbing, and fragmentation of neurites. DNA fragmentation was also confirmed by the use of the in situ DNA end labeling assay. In addition, aurintricarboxylic acid, an inhibitor of the apoptotic endonuclease, partially protected against camptothecin-induced neuronal death. The toxicity of stereoisomers of a camptothecin analogue was stereospecific, demonstrating that toxicity was a result of inhibition of topo-I. The difference in sensitivity to camptothecin between neurons and astrocytes correlated with their transcriptional activity and level of topo-I protein expression. These data indicate important roles for topo-I in postmitotic neurons and suggest that topo-I inhibitors can induce apoptosis independent of DNA synthesis. We suggest a model based on transcriptionally mediated DNA damage, a novel mechanism of action of topo-I poisons.