[Health status and its effects on the work of national education nurses]. / Santé ressentie et implication au travail des infirmier(e)s de l'Education nationale.

This study presents a pedagogical work carried out with a group of 13 school nurses of the Academy of Rennes, as part of a course in survey methodology. A descriptive survey aiming to achieve a better understanding of experienced health status of nurses, and of its repercussions on the execution of their missions, was implemented during the course, as a result of the demand and the expertise of the participants. Overall, nurses report to be in good health. However, one can not underestimate the existence of a group at risk (5% of the sample) that often suffers somatic troubles accompanied by sleep disorders and anxiety, as these risks concern primarily permanent staff nurses working in boarding establishments, with half of them falling into this category. A demand for regular monitoring of their health was clearly expressed through the study. This may be the object of a subsequent study by an academic team.

Partial inhibition of brain succinate dehydrogenase by 3-nitropropionic acid is sufficient to initiate striatal degeneration in rat.

Chronic inhibition of succinate dehydrogenase (SDH) by systemic injection of the selective inhibitor 3-nitropropionic acid (3NP) has been used as an animal model for Huntington's disease (HD). However, the mechanisms by which 3NP produces lesions in the striatum are not fully characterized. A quantitative histochemical method was developed to study the level of regional SDH inhibition resulting from intraperitoneal injection of 3NP or chronic intoxication using osmotic pumps. The results showed that (a) 3NP was an irreversible SDH inhibitor in vivo, (b) the level of SDH inhibition in the striatum (the brain region most vulnerable to 3NP) was similar to that observed in other brain regions not affected by the toxin, such as the cerebral cortex, and (c) the neurotoxic threshold of SDH inhibition in the brain was 50-60% of control levels. The present study demonstrates that the selective degeneration in the striatum observed after chronic 3NP administration cannot be ascribed to a preferential inhibition of SDH in this particular brain region. This work also suggests that the partial decrease in the activity of the respiratory chain complex II-III reported in HD patients may be sufficient to induce the selective striatal degeneration observed in this disorder.

Riluzole protects from motor deficits and striatal degeneration produced by systemic 3-nitropropionic acid intoxication in rats.

The putative neuroprotective effect of riluzole was investigated in a rat model of progressive striatal neurodegeneration induced by prolonged treatment (three weeks, intraperitoneal) with 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase. Quantitative analysis of motor behaviour indicated a significant protective effect (60%) of riluzole (8 mg/kg/day) on 3-nitropropionic acid-induced motor deficits as assessed using two independent motor tests. Furthermore, quantitative analysis of 3-nitropropionic acid-induced lesions indicated a significant 84% decrease in the volume of striatal damage produced by 3-nitropropionic acid, the neuroprotective effect apparently being more pronounced in the posterior striatum and pallidum. In addition, it was checked that this neuroprotective effect of riluzole against systemic 3-nitropropionic acid did not result from a decreased bioavailability of the neurotoxin or a direct action of riluzole on 3-nitropropionic acid-induced inhibition of succinate dehydrogenase. We found that riluzole significantly decreased by 48% the size of striatal lesions produced by stereotaxic intrastriatal injection of malonate, a reversible succinate dehydrogenase inhibitor. Furthermore, the inhibition of cortical and striatal succinate dehydrogenase activity induced by systemic 3-nitropropionic acid was left unchanged by riluzole administration. The present results, consistent with a beneficial effect of riluzole in amyotrophic lateral sclerosis, suggest that this compound may be useful in the treatment of chronic neurodegenerative diseases.

Riluzole reduces incidence of abnormal movements but not striatal cell death in a primate model of progressive striatal degeneration.

Riluzole has been shown recently to increase life expectancy in patients with amyotrophic lateral sclerosis. A number of experimental studies also suggest that this compound may be a neuroprotectant. We have investigated in baboons whether riluzole would protect striatal neurons from a prolonged 3-nitropropionic acid (3NP) treatment and ameliorate the associated motor symptoms. In animals receiving 3NP and the solvent of riluzole, 12 weeks of high-dose 3NP treatment resulted in the appearance of persistent leg dystonia and significant increases in the incidence of three categories of abnormal movements and in the dyskinesia index in the apomorphine test (0.5 mg/kg i.m.). Quantitative assessment of these behavioral deficits using a video movement analysis system demonstrated a significant decrease in locomotor activity and peak tangential velocity in 3NP-treated animals compared to controls. Histological analysis showed the presence of severe, bilateral, striatal lesions, localized in both caudate and putamen. Cotreatment with riluzole (4 mg/kg i.p., twice daily) significantly reduced the dyskinesia index (-35%, P < 0.02) in the apomorphine test. In the quantitative behavioral analysis, riluzole significantly ameliorated the decrease in peak tangential velocity (P < 0.02) but not the decrease in locomotor activity observed after 3NP. Comparative histological analysis of the two groups of treated animals did not demonstrate a clear neuroprotective effect of riluzole. The present study suggests that one potential therapeutic interest for riluzole in neurodegenerative disorders may reside in the reduction of motor symptoms associated with striatal lesions.

Quantifiable bradykinesia, gait abnormalities and Huntington's disease-like striatal lesions in rats chronically treated with 3-nitropropionic acid.

Impairment in energy metabolism is thought to be involved in the aetiology of Huntington's disease. In line with this hypothesis, chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid to rats and monkeys produces selective striatal lesions similar to Huntington's disease. The present study examined whether rats treated with varying regimen of 3-nitropropionic acid could present motor abnormalities reminiscent of Huntington's disease symptomatology, correlated with Huntington's disease specific striatal symptomatology. Subacute 3-nitropropionic acid treatment (15 mg/kg per day intraperitoneally for 10 days) produced dramatic motor symptoms associated with extensive neuronal loss and gliosis in the lateral striatum as well as severe hippocampal degeneration in 50% of the cases. In contrast, chronic 3-nitropropionic acid treatment (10 mg/kg per day subcutaneously for one month) led to more subtle excitotoxic-like lesions, selective for the dorsolateral striatum and more closely resembling Huntington's disease striatal pathology. Animals with these Huntington's disease-like lesions showed spontaneous motor symptoms including mild dystonia, bradykinesia and gait abnormalities, which were barely detectable on visual inspection but could be readily identified and quantified by computerized video analysis. In these chronic animals, the degree of striatal neuronal loss was significantly correlated with the severity of spontaneous motor abnormalities, as is the case in Huntington's disease. The present study demonstrates that chronic low-dose 3-nitropropionic acid treatment in rats results in a valuable model of both the histological features and motor deficits which occur in Huntington's disease. Despite the interanimal variability in terms of response to 3-nitropropionic acid treatment, this rat model may be particularly useful for evaluating the functional benefits of new therapeutic strategies for Huntington's disease, particularly those aiming to reduce the severity of motor symptoms.

Chronic 3-nitropropionic acid treatment in baboons replicates the cognitive and motor deficits of Huntington's disease.

We showed recently that chronic administration of the mitochondrial inhibitor 3-nitropropionic acid (3NP) in primates produces various dyskinetic movements and dystonic postures associated with selective striatal lesions displaying many similarities with the pathological features of Huntington's disease (HD). In the present study, we examined whether such a toxic treatment could also induce frontal-type deficits similar to those observed in HD patients. Cognitive performances of 3NP-treated and control baboons were compared using the object retrieval detour task (ORDT), a test designed to assess the functional integrity of the frontostriatal pathway in human and nonhuman primates. During the same time, the motor function of each animal was assessed under spontaneous "no drug" conditions, and time-sampled neurological observations were used after apomorphine administration. A significant impairment in the ORDT was observed in the 3NP animals after 3-6 weeks of treatment, occurring in the absence of spontaneous abnormal movements by in the presence of apomorphine-inducible dyskinesias. Prolonged 3NP treatment resulted in the progressive appearance of spontaneous abnormal movements. Histological evaluation of these animals showed selective bilateral caudate-putamen lesions with sparing of the cerebral cortex, notably the prefrontal cortex. The present study demonstrates that chronic 3NP treatment replicates in primates the basic pathophysiological triad of HD, including spontaneous abnormal movements, progressive striatal degeneration, and a frontostriatal syndrome of cognitive impairment.

In vivo metabolites of N omega-nitro-L-arginine methyl ester: methanol and N omega-nitro-L-arginine.

N omega-nitro-L-arginine methyl ester (L-NAME) is commonly used as a selective inhibitor for in vivo studies of brain nitric oxide (NO) synthase. We aimed to study the fate of N omega-nitro-L-arginine [11C]methyl ester ([11C]L-NAME) using positron emission tomography in monkey and high performance liquid chromatography methods in dogs and rats. We found that [11C]L-NAME was rapidly (t1/2 = 2 min) metabolized into N omega-nitro-L-arginine (L-NA) and [11C]methanol which both had a slow rate of elimination. Although, in vivo, L-NAME administration leads to long-lasting NO synthase inhibition by L-NA, methanol which is a potent neurotoxin in primate may produce detrimental effects unrelated to NO synthase inhibition.