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Production of nitric oxide (NO) in nonobese diabetic islets of diabetic female mice is attributed to immunological diabetogenic events. Pharmacological function of the drug aminoguanidine, an inactivator of NO synthase during the diabetic process, is investigated. Inhibitory role of aminoguanidine is a function of inhibitor levels and quantity of spleen cells transported during the diabetic process. The action of the drug leads to a decline in the formation of NO, and postpones the onset of diabetes by three to eight days.

Pregnant nonobese diabetic (NOD) mice were treated with lymphotoxin-beta receptor immunoglobulin fusion protein (LTbetaR-Ig) or control human immunoglobulin on days embryonic day 11 (E11) and E14, and offspring were followed for the development of anti-beta-cell antibodies, islet pathology, and hyperglycemia. The development of anti-beta-cell surface antibodies was abrogated in treated mice compared with controls. Autopsy examination of the mice at 30 weeks of age revealed normal development of secondary lymphoid structures in the control animals; however, mice treated with LTbetaR-Ig had no axillary, inguinal, popliteal, or peripancreatic lymph nodes. Histological examination of the pancreata of the control mice revealed a severe and destructive mononuclear cellular infiltrate in the islets, whereas the islets of the LTbetaR-Ig-treated mice were devoid of any insulitis. None of the LTbetaR-Ig-treated mice (n = 22) developed diabetes; in contrast, 80% of the control mice (n = 46) developed diabetes at 1 year of age. The LTbetaR-Ig-treated mice did not contain diabetogenic T-cells. However, the treated mice developed diabetes upon inoculation with diabetogenic T-cells. In this model of spontaneous autoimmune diabetes, secondary lymphoid structures, most likely the peripancreatic lymph nodes, were essential for the development of pathologic anti-beta-cell autoimmunity. [ABSTRACT FROM AUTHOR]

A blended material composed of beta-tricalcium phosphate (beta-TCP) and fumaric acid (FA) was prepared using a mechanochemical process. The structure and properties of the TCP-FA material was probed using particle size analysis, infrared, (31)P and (13)C solid-state nuclear magnetic resonance (NMR) spectroscopy, powder X-ray diffraction and calcium bioavailability. NMR studies showed that orthophosphate environments within beta-TCP remain largely unaffected in the presence of FA during mechanochemical processing; alternately, (13)C data indicated the carboxylic groups of FA are strongly affected during processing with beta-TCP. X-ray results reveal beta-TCP diffraction plane shifting with lattice contractions likely arising at the C(3) symmetry site. While milled beta-TCP (mTCP) produces a higher flux of bioavailable calcium relative to native beta-TCP, the mechanochemical conditioning of TCP-FA generates more than seven times the level of ionic calcium relative to mTCP. Collectively, the results from these studies indicate FA interfaces with calcium oxide polyhedra of the beta-TCP hexagonal crystal lattice, especially with the underbonded CaO(3) cluster manifested within the C(3) symmetry site of the beta-TCP motif. An in vitro remineralization/demineralization pH cycling dental model was then used to assess the potential of the TCP-FA material in reversing early stage non-cavitated enamel lesions. Characterization of the remineralization via surface and longitudinal microhardness measurements demonstrated that the TCP-FA material provides statistically superior remineralization relative to milled and native beta-TCP., (Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)