Decreased inflammation and augmented expression of trophic factors correlate with MOG-induced neuroprotection of the injured nigrostriatal system in the murine MPTP model of Parkinson's disease.

The response of the immune system during injury of the central nervous system may play a role in protecting neurons. We have previously reported that immunization with MOG 35-55 prior to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced injury of the dopaminergic system promotes less dopamine depletion and less dopaminergic damage of neurons in mice. In this study, we evaluate the influence of MOG immunization on the inflammatory reaction that occurs at the place of injury. C57Bl male mice, 2 and 12 months old, received i.p. injections of MPTP (40 mg/kg) and some groups animals also received an additional injection with myelin oligodendrocyte glycoprotein (MOG) 35-55 in CFA 6 days before MPTP administration. MPTP caused a common inflammatory reaction characterized by microglial activation, infiltration of T cells into the substantia nigra and striatum and increased expression of mRNA encoding pro-inflammatory cytokines (IL-1 beta, TNFalpha, INF gamma) and trophic factors (TGFbeta, GDNF). MOG immunization prior to MPTP administration significantly diminished the microglial reaction and reduced the levels of infiltrating CD8+ lymphocytes. The number of CD4+ T cells remained at the same level as in the MPTP group. Expression of pro-inflammatory cytokines was diminished. The mRNA expression of GDNF was significantly higher in the MOG pretreated mice relative to the MPTP group, both in the 2 month old and 12 month old groups. Since MOG immunization prior to MPTP intoxication appears to prevent nigrostriatal injury, the observed decrease of inflammation and increase of GDNF mRNA expression in the injured areas might represent one of the mechanisms of observed neuroprotection.

The impact of preconception counseling on pregnancy outcomes. The experience of the Maine Diabetes in Pregnancy Program.

OBJECTIVE: To determine if a noncentralized, statewide program could be established to educate health-care providers and women with pregestational diabetes on available strategies to prevent adverse outcomes in pregnancies complicated by diabetes. Characteristics of women who participated in the program and the outcomes of their pregnancies are evaluated. RESEARCH DESIGN AND METHODS: A network of regional providers caring for pregnant women with diabetes was developed. Continuing education sessions were delivered to both providers and women with existing diabetes on the importance of preconception counseling. RESULTS: Maine health-care providers collaborated on the development and adoption of three patient-care guidelines that address preconception counseling, prenatal care, and contraception for women with established diabetes. A total of 185 pregnancies among 160 women with pregestational diabetes reporting estimated delivery dates between 1 January 1987 and 31 December 1990 were identified. Of the total pregnancies, 62 (34%) occurred in women who received preconception counseling: among these 62 pregnancies were one major congenital defect (1.6%) and four fetal or neonatal deaths (6.4%). Among the 123 (66%) pregnancies occurring in women that had not received preconception counseling, 8 (6.5%) infants were born with congenital abnormalities, and 26 (21.1%) fetal or neonatal deaths were documented. CONCLUSIONS: A program promoting preconception counseling can be implemented on a statewide basis by using various health-care providers to deliver the program. Participation in such a program appears to be related to improved pregnancy outcomes among women with pregestational diabetes.

Self-reported data: reliability and role in determining program effectiveness.

This study was conducted to assess the reliability of self-reported hospitalization data, as well as the appropriateness of using self-reported data in evaluating the effectiveness of the Maine Ambulatory Diabetes Education and Follow-Up (ADEF) program. A Maine Blue Cross/Blue Shield (BC/BS) inpatient claims file was used as the reference source to verify self-reported hospitalization data. For a sample of 99 BC/BS subscribers who attended the ADEF program, 77% of the study participants accurately self-reported hospitalization patterns over a 12-mo time period before attending the education program, and 81% of the participants accurately self-reported hospitalization patterns during a posteducation follow-up time period. The reference BC/BS claims data documented a reduction in hospitalizations for the study participants similar to that reported using the ADEF self-reported hospitalization data. The Maine Diabetes Control Project used the self-reported hospitalization data in combination with selected reference claims data to secure third-party reimbursement for the Maine ADEF Program.

Interdependence of Na+ and Cl- transport in dog tracheal epithelium.

Previous studies showed active transport of Cl- toward and of Na+ away from the luminal surface of dog tracheal epithelium. The possible interdependence of Cl- and Na+ fluxes has not been explored fully in this preparation. The purpose of the present study is to investigate the relationship between these fluxes. Substituting choline for Na+ in the media bathing dogs tracheal epithelium reduced net Cl- transport toward the lumen from 1.86 +/- SE 0.27 to 0.49 +/- SE 0.20 mueq.cm-2.h-1. Substituting SO4(2-) For Cl- decreased net Na+ flux toward the lumen from -1.05 +/- SE 0.20 to -1.78 +/- SE 0.36 mueq.cm-2.h-1. Acetylcholine (5 x 10(-4) M) and terbutaline (10(-5) M) increased and furosemide (10(-3) M) decreased net Cl- transport toward the lumen in control, but not in Na+ free bathing media. Acetylcholine increased net Na+ flux toward the lumen in control, but not in Cl- free bathing media. Thus this study showed that 1) in media lacking Na+, net Cl- flux toward the lumen is decreased, and vice versa, 2) the increases in Cl- transport toward the lumen due to acetylcholine and terbutaline and the decrease due to furosemide required Na+ and 3) in the increase in Na+ flux toward the lumen due to acetylcholine required Cl-. These findings indicate that there is an interdependence of Cl- and Na+ fluxes in dog tracheal epithelium.

Effect of calcium on ion transport and electrical properties of tracheal epithelium.

Active transport of Cl- toward the tracheal lumen and Na+ away from the lumen creates an electrical potential difference across dog tracheal epithelium. This study examined in vitro the effect of varying calcium concentration in the bathing media on the ion transport and electrical properties of dog tracheal epithelium. In six pairs of epithelia, changing calcium concentration from 1.9 to 0 mM resulted in a significant decrease in electrical resistance, from 318 +/- 36 to 214 +/- 24 omega.cm2. Short-circuit current and net Cl- and Na+ fluxes measured under short-circuit conditions were not changed significantly. Changing calcium concentration from 1.9 to 10 mM resulted in no significant change from control in the electrical properties nor in net Cl- and Na+ fluxes (short-circuit conditions). Histamine (10(-4) M) produced a significantly smaller increase in short-circuit current in 0 than in 1.9 mM Ca2+ (+5 +/- 2 vs. +12 +/- 2 microamperemeter/cm2). However, electrical changes were not significantly different in 1 or 10 mM Ca2+. These results indicate that calcium lack increased permeability of tracheal epithelium and that the increase in short-circuit current due to histamine depended in part on calcium.