Effects of systemic 3-nitropropionic acid-induced lesions of the dorsal striatum on cannabinoid and µ-opioid receptor binding in the basal ganglia

Systemic administration of 3-nitropropionic acid (3NPA) in experimental animals produces bilateral striatal lesions similar to those seen in Huntington’s disease (HD) caudate and putamen. [³H]-CP55,940 binding to cannabinoid receptors in human basal ganglia nuclei has been shown to be highly susceptible to the earliest pathological changes in the HD brain. In this study, to assess further the suitability of 3NPA-induced striatal lesions as a model for HD neuropathology, we examined the effects of striatal lesions induced by the systemic administration of 3NPA on the binding of [³H]-CP55,940 to pre- and postsynaptic cannabinoid receptors in striatum, globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata and also the effect of 3NPA-induced striatal lesions on the binding of [³H]-DAMGO to μ-opioid receptors in striatal striosomes. Systemic administration of 3NPA induced bilateral and symmetrical lesions in dorsolateral striatum. Within the lesion core, [³H]-CP55,940 and [³H]-DAMGO binding density was reduced to background levels. Beyond the immediate borders of the central core of the 3NPA-induced lesion, striatal binding density was not significantly different from that measured in unlesioned rats. [³H]-CP55,940 binding in globus pallidus, entopeduncular nucleus and substantia nigra in 3NPA-lesioned rats was significantly reduced compared to controls, and the individual decreases were similar for each site. However, these reductions were statistically marginal. These data suggest that, while producing striatal lesions which bear some similarity to those seen in HD, the consequences of 3NPA for striatopallidal and striatonigral efferent projections do not reflect the reported neurodegenerative changes seen in the HD brain. Received: 18 November 1998 / Accepted: 12 July 1999     

Effects of indomethacin and polyunsaturated fatty acid diet on exercise-induced hypoxaemia in master athletes

We have previously reported a reduction in exercise-induced hypoxaemia following polyunsaturated fatty acid supplementation (PUFA). Although this might have been explained by increases in membrane fluidity, a clear explanation could not be provided due to potentially confounding influences of series-2 prosta- glandin mediated effects resulting from PUFA. In this investigation, ten master athletes [mean age 48.1 (SEM 6) years, maximal oxygen uptake (V˙O_{2 max} ) 3.39 (SEM 0.21) l?·?min^?1] completed a maximal cycling test (Ctrl) which was repeated after the administration of 150 mg of indomethacin to inhibit prostaglandin synthesis, both before and after 6 weeks of 3.66-g PUFA?·?day^?1. Cardiorespiratory parameters were obtained simultaneously with brachial arterial blood sampling for partial pressure of oxygen in arterial blood (P _aO₂), partial pressure of carbon dioxide in arterial blood (P _aCO₂), pH, oxygen saturation in arterial blood and lactate concentration determinations. A significant decrease in P _aO₂ (mmHg) from rest [93 (SEM 1.5)] was observed for exercise intensities of more than 40% V˙O_{2 max} in Ctrl reaching 75.9 (SEM 2.1) at V˙O_{2 max} . PUFA resulted in a 5.0 (SEM 0.68) mmHg upward shift (P?P _aO₂–oxygen uptake relationship, reducing the difference in partial pressure of oxygen between alveolar air and arterial blood (P _(A?a)O₂) at V˙O_{2 max} [Ctrl 36 (SEM 1.6) vs PUFA 33 (SEM 2.2) mmHg] while P _aCO₂, remained unchanged. Indomethacin had no effect on either P _aO₂, ideal partial pressure of oxygen in alveolar gas or P _(A?a)O₂ in either Ctrl or after PUFA. In contrast, the fall in pH was significantly reduced after indomethacin while V˙CO₂, P _aCO₂ and lactacidaemia remained unchanged. These observations confirm an effect of PUFA on exercise P _aO₂ behaviour which does not appear to be mediated by the influence of a series-2 prostaglandin.     

Exercise-induced hypoxaemia in master athletes: effects of a polyunsaturated fatty acid diet

Exercise-induced hypoxaemia (EIH) has been associated with an oxygen diffusion limitation. Because polyunsaturated fatty acids (PUFA) administration can modify cell membrane fluidity, we hypothesized that the importance of EIH could be reduced after a 6-week PUFA diet. Resting pulmonary functions and a maximal cycling test were performed before and after the diet, in eight master athletes [48 (SD 6 years)]. The partial pressure. of O₂ in arterial blood (PaO₂), alveolar ventilation ( ) and ideal alveolar-arterial oxygen partial pressure difference (P(A _i–a)O₂) were obtained at each exercise intensity. The extent of EIH at maximal exercise was significantly lower after PUFA [P_aO₂ –17.2 (SEM 1.9) vs –12.9 (SEM 2.2)]. Before PUFA, accounted for 50% of the variance in the fall inP(A _i–a) for intensities below 80% maximal oxygen uptake ( ) andP(A _i–a)O₂ for 60% between 70% and 100% . After PUFA, the reduction in EIH was highly correlated (r ² = 0.85;P < 0.001) to resulting changes inP(A_ii–a)O₂ and resting pulmonary diffusing capacity but not with changes in ideal alveolar partial pressure of oxygen. The improvement in EIH following PUFA could be related to an increase in alveolar-arterial oxygen conductance following improved pulmonary diffusion.     

Platelets and bronchospasm

The intrathoracic accumulation of radiolabelled platelets and concomitant changes in airway resistance have been recorded continuously in anaesthetised guinea pigs. Platelet-activating factor (PAF-acether) and antigen (in sensitised animals) elicited dose-related intrathoracic accumulation of platelets that could be associated with an increase in airway resistance. Maximal increases in airway resistance preceded maximal increases in platelet accumulation. Low doses of antigen could elicit substantial platelet accumulation, without detectable changes in lung function. It is concluded that physical obstruction of the pulmonary vasculature is not the sole determinant of platelet-dependent bronchoconstriction.     

A longitudinal study of gamma-interferon production by peripheral blood mononuclear cells from breast- and bottle-fed infants.

Production of gamma-interferon (gamma-IFN) in vitro by peripheral blood mononuclear cells (PBMC) from 15 breast-fed and 15 bottle-fed infants has been studied from birth to 9 months of age and compared with production by adult cells. Using a Terasaki plate microculture system with serum-free medium, PBMC were stimulated with staphylococcal enterotoxin A (SEA) and gamma-IFN production was assessed by an immunoradiometric assay. Cord blood mononuclear cells (CBMC) and PBMC from all infants secreted large quantities of gamma-IFN. The levels secreted did not change significantly with age over the 9 months of the study, nor did they differ from the levels secreted by adult cells. Cells from the bottle-fed infants secreted slightly more gamma-IFN than cells from breast-fed infants, but this difference was not significant. These results indicate that the potential for PBMC to secrete gamma-IFN in vitro is fully developed at birth in full-term infants and cannot therefore be further influenced by subsequent breast- or bottle-feeding. In addition, the greater susceptibility of infants than adults to certain bacterial and viral infections cannot be attributed to a deficiency in the potential of infant cells to secrete gamma-IFN in vitro.     

Clinical characterization of 42 oligospermic or azoospermic men with microdeletion of the AZFc region of the Y chromosome,and of 18 children conceived via ICSI

BACKGROUND: Severe spermatogenic compromise may be the result of a Y-chromosomal deletion of the AZFc region. Prior studies are limited to relatively small numbers of AZFc-deleted men. In this study, we have fully characterized 42 infertile men with a Y chromosome microdeletion strictly confined to the AZFc region, and we report on 18 children conceived through the use of ICSI. METHODS: A total of 42 oligospermic or azoospermic men had AZFc deletions. History, physical examination, karyotype, FSH, LH, testosterone, testis histology and results of ICSI using ejaculated or testis sperm were retrospectively accumulated in two academic clinical practices. RESULTS: All men were somatically healthy. Karyotypes were 46,XY in all but two men. FSH, LH, testosterone and testis histology could not differentiate those with oligospermia or azoospermia, nor could they predict whether sperm could be found in harvested testis tissue. Paternal age was not increased. Sperm production appeared stable over time. The results of ICSI were not affected by the AZFc deletion. All but one of the offspring were healthy. The sons inherited the AZFc deletion with no increase in length. CONCLUSIONS: AZFc-deleted men are somatically healthy, will most likely have useable sperm, will have stable sperm production over time and will have a good chance to experience biological paternity, but their sons will also be AZFc-deleted.