[The French Armed Forces Biomedical Research Institute (IRBA) and wastewater-based epidemiology: Applicability and relevance in armed forces]. / L'Institut de recherche biomédicale des armées (IRBA) et l'épidémiologie des eaux usées : intérêt pour les forces armées.

The French Armed Forces Biomedical Research Institute (IRBA) deeply involved in research on SARS-COV-2, participated in the creation of the Obépine sentinel network in charge of detecting, qualifying and quantifying the virus genome in wastewater in France. During this pandemic, wastewater-based epidemiology has proven to be a first class public health tool for assessing viral dynamics in populations and environment. Obépine has also conducted research demonstrating the low infectivity of faeces and wastewater and allowed for early detection of epidemic waves linked to new variants. The IRBA has adapted this powerful tool to the monitoring of viral infections on board the aircraft carrier Charles-de-Gaulle in order to get an operational system for anticipation after the first local outbreak in 2020. The presence of this surveillance and anticipation tool has allowed a better management of SARS-CoV-2 contingent introductions on board during stopovers or crewmembers entries. The combination of a mandatory vaccination protocol and the surveillance of viral circulation in black waters has made it possible to identify and locate cases, and thus to continue the operational mission in the COVID-19 environment while limiting the spread and preserving the health of the crew. This innovative tool can easily be redirected to the search for any other pathogens in blackwater or even, in the long term, to ensure health surveillance of any military establishment, at sea or on land, in France or on overseas bases.

Cardiac Coherence Training to Reduce Anxiety in Remitted Schizophrenia, a Pilot Study.

Health care that addresses the emotional regulation capacity of patients with schizophrenia confronted with daily stress may contribute to a less anxious life. A psycho-physiological training [cardiac coherence training (CCT)] focusing on emotion regulation is known to decrease anxiety for healthy individuals. We performed a pilot cross sectional survey to explore the benefits of CCT for clinically stable patients with schizophrenia. Ten patients were enrolled in the program consisting of twelve weekly 1-h session programs monitored over a 2-month period. Standardised questionnaires were used before and after the intervention to assess anxiety, well-being outcomes, and how patients deal with stress and stressors. Results showed that this quite-well accepted intervention improved (or tended to improve) well-being outcomes, state-anxiety, and emotional stressors evaluation. The successful transformations were higher for patients with the highest clinical and emotional suffering. Thus, this pilot study revealed that CCT may help patients with schizophrenia to deal with anxiety in daily life.

[How to assess mindfulness? Problems and future]. / Comment mesurer la mindfulness ? Problèmes et perspectives.

INTRODUCTION: The concept of mindfulness is characterized by awareness and acceptance of experiences; flexible regulation of attention; an objective receptivity to experience and an orientation to the here-and-now. Interest in 'mindfulness' and 'mindfulness meditation' is recent and growing both at the levels of research and of clinical practice in the West as mindfulness is associated with health and well-being. It (mindfulness) is attained by the practice of certain types of meditation. One of the current key challenges is to evaluate and measure the level of mindfulness of a subject and its evolution. OBJECTIVES: The paper proposes a reflexion on the concept of mindfulness with a view to improving the operational evaluation of mindfulness level for clinical and non-clinical subjects. METHODS: First, the problems with the use of existing self-report questionnaires assessing mindfulness level are discussed. Second, an analysis of the cognitive processes that come into play in mindfulness acquisition (by meditation) can highlight the significance of certain cognitive tools in a more accurate evaluation of the level of mindfulness of individuals. CONCLUSION: Self-regulation of attention, and orientation to lived experience could be operational candidates for assessing the level of mindfulness. The pertinence of well-known paradigms evaluating self-regulation of attention and orientation to experience are discussed.

[The history of Mindfulness put to the test of current scientific data: unresolved questions]. / L'histoire de la Mindfulness à l'épreuve des données actuelles de la littérature: questions en suspens.

The first part of this paper describes the long history of the concept of Mindfulness. Contrary to the belief that Mindfulness only has Buddhist and Hindu origins, it is also rooted in Jewish, Islamic and Christian religions. Furthermore, western philosophers have described a mindful path to become more aware of thoughts, feelings, and bodily sensations. Mindfulness can be considered as a universal human ability embodied to foster clear thinking and open-heartedness. As such, this form of being requires no particular religious or cultural belief system. The current acceptance of what a mindful path is, refers to a psychological quality that involves bringing one's complete attention to present experience on a moment-to-moment basis, in a particular way: in the present moment, and nonjudgmentally. Although such a definition is well accepted in France, the French translation for Mindfulness is not easy to use: being conscious and being aware are translated with the same French word. The French language fails to clearly separate the dimensional attributes of a mindful subject from the ways for developing mindfulness through formal meditation practice. In line with this conception, stability and assessments of Mindfulness mainly were examined. How this disposition allows the development of concentration, attention and acceptance moment by moment in a nonjudgmental way is described in the second part. Particular attention is paid to its positive effects in several aspects of mental and physical health. In particular, positive effects on the ability to cope with stress are described from a physiological point of view. Third, this article intends to present neurobiological aspects currently proposed to explain the benefits of Mindfulness meditation. Modifications of cerebral networks and neurobiological functioning are described in relation to expertise in meditation practice. The hypothesis of the role of meditation on neuroplasticity is also discussed. Furthermore, the specific impact of Mindfulness meditation practice on these mechanisms will be considered in comparison with relaxation techniques. With the increasing growth of well-designed and well-controlled meditation research, however, future studies will be needed to compare between different meditation techniques. This will enable researchers to outline the effects of the technique-specific differences on behavior, cognitive function, underlying physiology and neurobiology and clinical effectiveness. Finally, the most recent data on the changes in functioning of a resting brain (Brain Default Mode) induced by a Mindfulness practice, demonstrate differences in the default-mode network that are consistent with decreased mind-wandering. That is a way to better understand possible neural mechanisms of meditation for health benefits of Mindfulness.

Posture analysis in predicting fall-related injuries during French Navy Special Forces selection course using machine learning: a proof-of-concept study.

INTRODUCTION: Injuries induced by falls represent the main cause of failure in the French Navy Special Forces selection course. In the present study, we made the assumption that probing the posture might contribute to predicting the risk of fall-related injury at the individual level. METHODS: Before the start of the selection course, the postural signals of 99 male soldiers were recorded using static posturography while they were instructed to maintain balance with their eyes closed. The event to be predicted was a fall-related injury during the selection course that resulted in the definitive termination of participation. Following a machine learning methodology, we designed an artificial neural network model to predict the risk of fall-related injury from the descriptors of postural signal. RESULTS: The neural network model successfully predicted with 69.9% accuracy (95% CI 69.3-70.5) the occurrence of a fall-related injury event during the selection course from the selected descriptors of the posture. The area under the curve value was 0.731 (95% CI 0.725-0.738), the sensitivity was 56.8% (95% CI 55.2-58.4) and the specificity was 77.7% (95% CI 76.8-0.78.6). CONCLUSION: If confirmed with a larger sample, these findings suggest that probing the posture using static posturography and machine learning-based analysis might contribute to inform risk assessment of fall-related injury during military training, and could ultimately lead to the development of novel programmes for personalised injury prevention in military population.

How do we fight COVID-19? Military medical actions in the war against the COVID-19 pandemic in France.

'We are at war', French President Emmanuel Macron said in an address to the nation on 16 March 2020. As part of this national effort, the French Military Medical Service (FMMS) is committed to the fight against COVID-19. This original report aimed to describe and detail actions that the FMMS has carried out in the nationwide fight against the COVID-19 pandemic in France, as well as overseas. Experts in the field reported major actions conducted by the FMMS during the COVID-19 pandemic in France. In just few weeks, the FMMS developed ad hoc medical capabilities to support national health authorities. It additionally developed adaptive, collective en route care via aeromedical and naval units and deployed a military intensive care field hospital. A COVID-19 crisis cell coordinated the French Armed Forces health management. The French Military Centre for Epidemiology and Public Health provided all information needed to guide the decision-making process. Medical centres of the French Armed Forces organised the primary care for military patients, with the widespread use of telemedicine. The Paris Fire Brigade and the Marseille Navy Fire Battalion emergency departments ensured prehospital management of patients with COVID-19. The eight French military training hospitals cooperated with civilian regional health agencies. The French military medical supply chain supported all military medical treatment facilities in France as well as overseas, coping with a growing shortage of medical equipment. The French Armed Forces Biomedical Research Institute performed diagnostics, engaged in multiple research projects, updated the review of the scientific literature on COVID-19 daily and provided expert recommendations on biosafety. Finally, even students of the French military medical academy volunteered to participate in the fight against the COVID-19 pandemic. In conclusion, in an unprecedented medical crisis, the FMMS engaged multiple innovative and adaptive actions, which are still ongoing, in the fight against COVID-19. The collaboration between military and civilian healthcare systems reinforced the shared objective to achieve the goal of 'saving the greatest number'.

Cinnamon improves insulin sensitivity and alters the body composition in an animal model of the metabolic syndrome.

Polyphenols from cinnamon (CN) have been described recently as insulin sensitizers and antioxidants but their effects on the glucose/insulin system in vivo have not been totally investigated. The aim of this study was to determine the effects of CN on insulin resistance and body composition, using an animal model of the metabolic syndrome, the high fat/high fructose (HF/HF) fed rat. Four groups of 22 male Wistar rats were fed for 12 weeks with: (i) (HF/HF) diet to induce insulin resistance, (ii) HF/HF diet containing 20 g cinnamon/kg of diet (HF/HF + CN), (iii) Control diet (C) and (iv) Control diet containing 20 g cinnamon/kg of diet (C + CN). Data from hyperinsulinemic euglycemic clamps showed a significant decrease of the glucose infusion rates in rats fed the HF/HF diet. Addition of cinnamon to the HF/HF diet increased the glucose infusion rates to those of the control rats. The HF/HF diet induced a reduction in pancreas weight which was prevented in HF/HF+CN group (p<0.01). Mesenteric white fat accumulation was observed in HF/HF rats vs. control rats (p<0.01). This deleterious effect was alleviated when cinnamon was added to the diet. In summary, these results suggest that in animals fed a high fat/high fructose diet to induce insulin resistance, CN alters body composition in association with improved insulin sensitivity.

[Intravenous thrombolysis with rt-PA in stroke: experience of the French military hospital of Toulon from September 2003 to June 2009]. / Expérience de la thrombolyse intraveineuse des infarctus cérébraux à l'hôpital d'instruction des armées Sainte-Anne de Toulon de septembre 2003 à juin 2009.

INTRODUCTION: Since 2003, intravenous thrombolysis with rt-PA for stroke victims has been largely developed in the military hospital of Toulon. We report the results of our practice and compare them with the literature. We also sought to identify predictive factors of favorable outcome after thrombolysis. METHODS: All patients treated with rt-PA for a stroke in the carotid territory between September 2003 and June 2009 were prospectively included. Disability was assessed at 3 months with the modified Rankin Scale (m-RS); outcome was considered unfavorable if m-RS score was above 2. Multivariate analysis was then performed to identify parameters correlating with poor and favorable outcome at 3 months follow-up. RESULTS: One hundred and one patients were included in this study (mean initial National Institute of Health Stroke Scale [NIHSS]: 15.2). 53.4% had a Rankin score higher than 2 at 3 months follow-up. The absence of diabetes mellitus, low NIHSS score on admission, short time from stroke onset to treatment, and prior statin use were identified as independent predictive factors of favorable functional outcome. CONCLUSIONS: After 6 years of activity, our stroke unit has results that appear similar to those of the French and international trials in terms of safety and efficacy. Efficacy of rt-PA in our series is poor for strokes caused by large-vessel atherothrombotic changes and cervical artery dissection due to high incidence of internal carotid thrombosis in these cases. Our studies also suggest that prior statin use may be an independent predictive factor of favorable outcome after thrombolysis.

Acute emotional stress and high fat/high fructose diet modulate brain oxidative damage through NrF2 and uric acid in rats.

Studies focusing on the interaction of dietary and acute emotional stress on oxidative stress in cortex frontal and in brain mitochondria are scarce. Dietary-induced insulin resistance, as observed in Western diets, has been associated with increased oxidative stress causing mitochondrial dysfunction. We hypothesized that acute emotional stress could be an aggravating factor by impacting redox status in cortex and brain mitochondria. Thus, the aim of the present study was to evaluate the combination of an insulin resistance inducing high-fat/high-fructose (HF/HFr) diet and acute emotional stress on brain oxidative stress in rats. We measured several oxidative stress parameters (carbonyls, FRAP, TBARS assays, GSH, GSSG, oxidized DNA, mRNA expression of redox proteins (Nrf2), and uric acid). The HF/HFr diet resulted in increased oxidative stress both in the brain mitochondria and in the frontal cortex and decreased expression of the Nrf2 gene. The emotional stress induced an oxidative response in plasma and in brain mitochondria of the control group. In the HF/HFr group it triggered an increase expression of the redox transcription factor Nrf2 and its downstream antioxidant genes. This suggests an improvement of the redox stress tolerance in response to an enhanced production of reactive oxygen species. Accordingly, a blunted oxidative effect on several markers was observed in plasma and brain of HF/HFr-stressed group. This was confirmed in a parallel study using lipopolysaccharide as a stress model. Beside the Nrf2 increase, the stress induced a stronger UA release in HF/HFr which could take a part in the redox stress.

Emotional overactivity in patients with irritable bowel syndrome.

BACKGROUND: Negativity is often observed in patients with irritable bowel syndrome (IBS). No study has examined their emotional expressiveness as a marker of emotional reactivity. We investigated IBS patients' vulnerability to an emotional load by associating their expressiveness with psychological and neurophysiological assessments. We hypothesized that IBS would be characterized by a lack of expressiveness coupled with high scores in psychological and neurophysiological parameters. METHODS: We assessed the emotional facial expressions (EMFACS), psychological (anxiety, depression, alexithymia), and neurophysiological (cortisol, heart rate variability (HRV)) parameters of 25 IBS patients and 26 healthy controls (HC) while they watched fear-eliciting movie extracts. KEY RESULTS: Overall, the task elicited an increase in state anxiety and consistent HRV responses. However, IBS patients differed from HC as they displayed more sadness and tended to display more rage. Contrary to HC, IBS patients showed an increase in heart rate and a decrease in parasympathetic regulation, reflecting an enhanced responsiveness corroborated by higher scores in depression and state anxiety. Consistent with their higher difficulty in identifying feelings, a component of alexithymia positively correlated with their expressions of rage, they were not aware of their increase in anxiety during the task, whereas HC were. No linear relationship between patients' expressions and their neurophysiological responses was found. CONCLUSIONS & INFERENCES: Irritable bowel syndrome patients displayed greater emotional expressiveness with negative prevalence. This reflects an emotional vulnerability potentially related to low regulation skills and underscores the importance of considering the central dysregulation hypothesis in IBS as a promising avenue of research.

Decreased heat tolerance is associated with hypothalamo-pituitary-adrenocortical axis impairment.

When rats are exposed to heat, they adapt themselves to the stressor with a wide inter-individual variability. Such differences in heat tolerance may be related to particularities in the hypothalamo-pituitary-adrenocortical (HPA) axis activation. To further this hypothesis, 80 rats instrumented with a telemetric device for abdominal temperature (Tabd) measurement were separated into two groups. Sixty-eight rats were exposed during 90 min at an ambient temperature of 40 degrees C, and 12 rats to an ambient temperature of 22 degrees C. Heat-exposed rats were then divided into three groups using the a posteriori k-means clustering method according to their Tabd level at the end of heat exposure. Heat tolerant rats (Tol, n=30) exhibiting the lowest Tabd showed a slight dehydration, a moderate triglyceride mobilization, but the highest plasma adrenocorticotropic-hormone (ACTH) and corticosterone levels. Conversely, heat exhausted rats (HE, n=14) presented the highest Tabd, a higher degree of dehydration, a greater metabolic imbalance with the lowest plasma triglyceride level and the highest lactate concentration, as well as a lowest plasma corticosterone and ACTH levels. The fact that the proopiomelanocortin (POMC) mRNA content within the pituitary was low despite of a high c-fos mRNA level is also relevant. Current inflammatory processes in HE rats were underlined by lower inhibitory factor kappaBalpha (IkappaBalpha) mRNA and higher tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mRNA. In conclusion, data show that intolerance to heat exposure is associated to an HPA axis impairment, possibly related to changes occurring in the IkappaBalpha and TNF-alpha mRNA levels.

High-frequency stimulation of the hippocampus blocks fear learning sensitization and return of extinguished fear.

Patients with post-traumatic stress disorder (PTSD) present hippocampal (HPC) dysfunction, which may facilitate fear-related phenomena such as fear learning sensitization (i.e. potentiation of fear acquisition by initial fear conditioning (FC1)) and fear return (i.e. reactivation of extinguished fear). Fear return is sensitive to HPC high-frequency stimulation (HFS) in rats. The goal of the present study was to examine whether fear learning sensitization is also sensitive to HPC HFS in rats. We found in control conditions that, after FC1 (with 15 shock administrations) and extinction, conditioning in a different context with one shock administration was potentiated (proactive effect) and associated with fear return in the initial context (retroactive effect). Both phenomena were prevented by HPC HFS applied before the second conditioning. We also found that the effect of HPC HFS on fear learning sensitization required initial extinction. These findings suggest a pivotal role of the HPC in preventing proactive and retroactive effects of successive fear conditionings. These data also support the concept that HPC deactivation may be involved in fear learning sensitization and fear return in PTSD patients.

Differences in prefrontal cortex GABA/glutamate ratio after acute restraint stress in rats are associated with specific behavioral and neurobiological patterns.

In patients suffering from stress-related pathologies and depression, frontal cortex GABA and glutamate contents are reported to decrease and increase, respectively. This suggests that the GABA and/or glutamate content may participate in pathological phenotype expression. Whether differences in frontal cortex GABA and glutamate contents would be associated with specific behavioral and neurobiological patterns remains unclear, especially in the event of exposure to moderate stress. We hypothesized that an increase in prefrontal cortex GABA/glutamate ratio would be associated with a blunted prefrontal cortex activation, an enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activation and changes in behavior. Rats being restrained for 1-h were then tested in an open-field test in order to assess their behavior while under stress, and were sacrificed immediately afterward. The GABA/glutamate ratio was assessed by (1)H high-resolution magic angle spinning magnetic resonance spectroscopy ((1)H-HRMAS-MRS). The neurobiological response was evaluated through prefrontal cortex mRNA expression and plasma corticosterone levels. The stressed rats were distributed into two subgroups according to their high (H-G/g) or low (L-G/g) GABA/glutamate ratio. Compared to the L-G/g rats, the H-G/g rats exhibited a decrease in c-fos, Arc, Npas4, Nr4a2 mRNA expression suggesting blunted prefrontal cortex activation. They also showed a more pronounced stress with an enhanced rise in corticosterone, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), creatine kinase (CK) and lactate dehydrogenase (LDH) levels, as well as behavioral disturbances with decreased locomotion speed. These changes were independent from prefrontal cortex energetic status as mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) pathway activities were similar in both subpopulations. The differences in GABA/glutamate ratio in the frontal cortex observed in the stressed animals may participate in shaping individual differences in psychophysiological reactions.

Effects of MPTP on lever-pressing for light extinction in rats.

Rats were daily treated for seven days with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) at a dose of 20 mg/kg/day, i.p. Seven days after treatment withdrawal, the rats were individually tested in a brightly lit apparatus containing two levers: an active lever allowing periods of darkness, and an inactive one. The test was performed over two consecutive days, in 20-min sessions. While control rats had a higher number of total active lever pressings than inactive lever pressings, this was not the case for MPTP-treated rats. Control rats decreased their useless active lever pressings and inactive lever pressings across the two sessions, but MPTP-treated rats did not do either. The absence of the differential effect in rats injected with MPTP may be due to a reduction in reinforcement mechanisms caused by the mild depletion of dopamine in the striatum.

NMDA receptors are involved in dithiothreitol-induced hypothermia.

Sulfhydryl-reducing agents, such as dithiothreitol, modulate glutamate N-methyl-D-aspartate (NMDA) receptors. Since these receptors are involved in thermoregulatory processes, we studied the effects of their positive modulation, through a dithiothreitol-induced reduction of the receptor redox site, on thermoregulation in rats maintained at an ambient temperature of 20-22 degrees C. Given intraperitoneally at the dose of 25 and 50 mg x kg(-1), dithiothreitol induced dose-dependent hypothermia. The prior administration of 0.5 mg x kg(-1) of (+/-)-dizocilpine maleate (MK801), a non-competitive glutamate NMDA receptor antagonist, blocked most of the dithiothreitol-induced hypothermia. MK801 given alone was followed by slight transient hyperthermia. This confirms the involvement of NMDA receptors in thermoregulation and suggests that they might be under redox modulation.

Dopamine involvement in thermoregulatory responses to heat in rats.

The role of dopamine in thermoregulatory challenges was studied in rats exposed to thermoneutrality then to heat with pretreatment by SCH23390 (i.p., D1/D5 receptor antagonist), sulpiride (i.p., D2 receptor antagonist) or piribedil (i.p., D2/D3 receptor agonist). Heat exposure leads to a rise in rectal temperature followed by a steady plateau ending with a terminal increase. The duration of both heat exposure and the plateau increased largely after SCH23390 and rose slightly after sulpiride. Piribedil was ineffective on these parameters but lowered rectal temperature at thermoneutrality. It is suggested that the thermoregulatory failure observed in heat-exposed rats may implicate dopamine through D1/D5 and in a lesser extent through D2 receptors. The inefficacy of piribedil suggests that dysregulations in synaptic transmission may exist.

Inhibition of different types of nitric oxide synthase: effect on thermoregulation in the rat exposed to high ambient temperature.

Vascular and immunological mechanisms are both likely to be involved in heatstroke, this condition being preceded by a decrease in cerebral blood flow and an increase in brain cytokine concentrations. As the two mechanisms involve a nitridergic step, we analysed their respective role in heat tolerance by exposing vigil rats to heat after treatment with nitric oxide synthases (NOS) antagonists: non-specific inhibitors N(omega)-nitro-L-arginine (LNA) and N-nitro-L-arginine-methyl-ester (L-NAME); 7-nitroindazol (neuronal NOS inhibitor) and aminoguanidine (AG) (inducible NOS inhibitor). Heat exposure was interrupted when clinical signs occurred or when colonic temperature reached 43 degrees C. LNA and L-NAME dramatically reduced heat tolerance, while AG did not modify it. These results suggest the involvement of constitutive NOS in heat tolerance. Inducible NOS does not seem to be involved in the occurrence of heatstroke.

Voltametric assessment of brain nitric oxide during heatstroke in rats.

Anesthetized rats exposed to a high ambient temperature develop heatstroke with brain ischemia. Since nitric oxide (NO) plays an important role during normothermic ischemia, its cortical and cerebellar production were continuously assessed in pentobarbital anesthetized rats exposed to heat by using differential pulsed voltammetry. After 60 min at thermoneutrality, the rats were submitted to an ambient temperature of 40 degrees C until death. After 60 min in the heat, the rats were injected intraperitoneally with saline, MK801 (1 mg.kg(-1)), an antagonist of N-methyl-D-aspartate (NMDA) receptors, or L-arginine p-nitroanilide (L-ANA; 100 mg.kg(-1)), an inhibitor of NO synthase. Just before death, a 70% increase in NO production was observed in both the cerebellum and the cortex of saline-treated rats. The cortical increase in NO was not modified by MK801 while the NO signal was suppressed by L-ANA.

Clinical follow-up in the rat experimental model of African trypanosomiasis.

Animal models of Human African Trypanosomiasis (HAT) have been developed to understand the pathogenic mechanisms leading to the passage into the neurological phase, most of them referring to histological aspects but not clinical or behavioral data. Our study aimed at defining simple clinical and/or behavioral markers of the passage between the hemolymphatic phase and the meningo-encephalitic stage of the disease. Sprague-Dawley rats (n=24) were infected with Trypanosoma brucei brucei AnTat 1.1E. Food intake and body weight were measured daily from the day of infection until death. Hematocrit was measured twice a week. Behavioral disturbances were evaluated through an Open-field test. A sudden weight loss occurred on the twelfth day after infection, due to a significant drop of food intake starting two days before. The rats developed an anemic state shown by the hematocrit measurements. The Open-field test showed them to be less active and reactive as soon as the second week after infestation. A complementary histological study observed trypanosomes and inflammatory cells in the choroid plexus at the same period. These results are in favor of central nervous system functional disturbances. The observed weight loss is discussed as being a parameter of the entry in the meningo-encephalitic phase. The rat model reproduces neurological symptoms observed in the human disease and may prove to be useful for further neurohistological and therapeutic studies.

Heat stress, even extreme, does not induce penetration of pyridostigmine into the brain of guinea pigs.

Stress due to forced swimming was recently shown to allow penetration of pyridostigmine (PYR) into the brain of mice. Accordingly, it was suggested that in troops exposed to emotional stress under conditions of war, as during the Gulf War, the BBB may have unexpectedly become permeable to PYR thus leading to an increased frequency of CNS symptoms. In this study, the entry of PYR into the brain was investigated in guinea pigs subjected to different heat stress levels. In a first group, guinea pigs were maintained at room temperature for 2 hours, their core temperature remaining stable at about 39.8 degrees C. In a second group, animals were placed in a climatic chamber in order to keep their core temperature at 41.5 degrees C for 2 hours. In a third group, animals were subjected to a high ambient temperature (42.6 degrees C) during about 2 hours and developed heatstroke symptoms, their core temperature progressively increasing and reaching around 44.3 degrees C. In each group, the stress of the animals was assessed by measuring the increase of plasma cortisol level. PYR (0.2 mg/kg, s.c.) was injected 90 minutes after beginning the experiment. Penetration of the drug into the brain was examined by measurement of acetylcholinesterase (AChE) activity in the cortex, the striatum and the hippocampus of the animals 30 minutes after PYR administration. A passage of this drug into the brain was also evaluated autoradiographically after i.v. injection of tritiated PYR 90 minutes after the beginning of the experiment (100 microCi/animal). Whatever the group examined, no entry of PYR into the CNS could be detected. Exposure to an ambient temperature at 42.6 degrees C for 2 hours resulted by itself in a partial inhibition of cerebral AChE activity. Our results, which agree with previous data obtained in humans exposed to heat stress, are opposite to the recent research showing a central passage of PYR in mice following a forced swim stress test. This demonstrated that the penetration of PYR into the brain of rodents under stress depends on the experimental conditions used (animal species, nature of the stressor, etc.). Extrapolations to humans of results primarily obtained in rodents about central passage of a drug under stress must thus be done very carefully.