Effets de l’halothane sur la ventilation et les gaz du sang artériel chez le rat avec ou sans paralysie diaphragmatique

Certains patients atteints de paralysie diaphragmatique ou de dysfonctionnement diaphragmatique maintiennent leur ventilation par la mise en jeu d’autres muscles que le diaphragme. L’anesthésie, modifiant le fonctionnement de ces muscles, représente un risque potentiel chez ces patients. Afin d’évaluer ce risque, nous avons étudié les effets de l’halothane sur la ventilation et sur les gaz du sang artériel sur un modèle de paralysie diaphragmatique bilatérale, le rat phrénicectomisé. L’étude a été réalisée sur 43 rats. L’efficacité de la phrénicectomie a été contrôlée par l’observation directe, après laparotomie. La laparotomie n’entraine pas de modification des gaz du sang. Chez 23 rats, une laparotomie a été effectuée et une artère carotide a été cathétérisée. Chez 11 rats témoins, les nerfs phréniques ont été abordés, sans être sectionnés. Chez 12 rats, les phréniques ont été sectionnés. La ventilation a été mesurée par une technique pléthysmographique, chez les rats éveillés, avant et après l’opération, puis chez les mêmes rats anesthésiés avec 1,1%, d’halothane inspiré. Les gaz du sang ont été mesurés après l’opération chez les rats éveillés, puis anesthésiés. Chez les 23 rats opérés on observe, après l’opération, une diminution du poids et de la température centrale, plus importante chez les phrénicectomisés que chez les témoins. Chez les 11 rats témoins, après l’opération, la ventilation augmente, sans modification des gaz du sang. Chez ces rats, l’halothane provoque une diminution de la ventilation minute et de la PaO₂ et une augmentation de la PaCO₂. La phrénicectomie entraine chez les 12 rats, éveillés, une augmentation de la ventilation minute, une hypoxémie et une hypercapnie. Chez ces rats, l’halothane entraine le décès dans trois cas, une diminution de la ventilation minute et une hypercapnie et une hypoxémie importantes chez les neuf autres rats. Les modifications des gaz du sang sont plus importantes que chez les témoins anesthésiés. Chez le rat intact, l’halothane provoque des modifications des gaz du sang comparables à celles observées chez d’autres espèces et chez l’homme. La présente étude confirme les effets de l’halothane sur les muscles respiratoires autres que le diaphragme. Elle met en évidence le risque respiratoire majeur que l’anesthésie peut fair courir aux patients dont la ventilation est maintenue par d’autres muscles que le diaphragme.     

Effect of 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) enantiomers,major metabolites of phenytoin,on the occurrence of chronic-gingival hyperplasia: in vivo and in vitro study

The purpose of this study was to assess the possible role of the (R)- and (S)- enantiomers of the phenytoin metabolite p-HPPH in the pathogenesis of gingival hyperplasia (GH). About 98% of circulating p-HPPH is in the (S)-form. There were significant differences between patients with and without GH in (R)-p-HPPH level (0.055 vs 0.042 g·ml^–1), both enantiomer/racemate level ratios, and R/S enantiomeric ratio (0.0313 vs 0.0232); an increase in serum (R)-p-HPPH level was observed in patients with GH. In separate experiments, the effect of p-HPPH enantiomers on the proliferation of the normal human dermal fibroblast was studied. The in vitro study showed that (R)-p-HPPH selectively stimulated fibroblast growth. The results suggest that the least abundant metabolite, (R)-p-HPPH, is the most toxic with respect to gingival hyperplasia.     

Cardiac effects of contrast media in MR angiography: evaluation in an experimental model of myocardial ischemia

RATIONALE AND OBJECTIVES: The authors evaluated the cardiac tolerability of paramagnetic contrast agents for magnetic resonance (MR) angiography in an in vitro model of ischemic rat heart. MATERIALS AND METHODS: The left anterior descending coronary artery was temporarily occluded in a perfused rat heart model to induce cardiac ischemia and reperfusion. A dose of 0.4 mL of gadobenate dimeglumine, of gadopentetate dimeglumine, or of D-mannitol was injected directly into the aorta both during the ischemia and during the reperfusion period. The left ventricular pressure and heart rate were recorded. RESULTS: Myocardial ischemia resulted in decreased cardiac activity, with a reduction in left ventricular pressure and heart rate. A further decrease in cardiac activity was temporarily induced by injection of contrast medium during both the ischemic and early reperfusion phases. Less marked responses were induced by a hyperosmolal solution of mannitol. CONCLUSION: These results suggest that the transient cardiac effects induced by bolus injection of paramagnetic contrast medium may be regarded as the combined effects of the osmotoxicity of the contrast medium solution and the chemotoxicity of the contrast medium molecule.     

Morbus sacer in Africa: some religious aspects of epilepsy in traditional cultures

Epilepsy when manifested as grand mal seizure provokes strong and ambivalent feelings in those witnessing it. Terms such as morbus sacer, denoting both a sacred and demoniac condition, or folk names indicating divine punishment, have expressed these feelings in European societies from antiquity to the Middle Ages and beyond. An atmosphere of fear, shame and mysticism surrounds epilepsy even in our days in many non-Western and also in Western cultures. In the course of work and studies in Tanzania, where I organized the Mahenge Clinic for Epilepsy in 1960, and in other parts of Africa, I found that epilepsy is conceived of as an "African' affliction, a manifestation of supernatural forces that makes it difficult to reach epilepsy sufferers with modern medical treatment. Epilepsy is traditionally looked on as caused by ancestral spirits or attributed to possession by evil spirits. It is also thought to be due to witchcraft, and "poisoning," and often taken to be contagious. Epilepsy may, under Christian missionary teaching, have come to be considered as due to demoniac possession or divine punishment for sins, in accordance with biblical examples. In many parts of Africa, syncretic amalgamation of indigenous traditions with Judeo-Christian doctrines influenced popular attitudes toward epilepsy. We demonstrated that persistent efforts at health education in the context of organized treatment of epilepsy can result in a change of popular notions about epilepsy and consequently lead to significant improvement in the quality of life of epilepsy sufferers.     

Early postnatal treatment with peptide preparations influences spatial navigation of young and adult rats

The brain derived peptidergic drug Cerebrolysin has been found to support the survival of neurons in vitro and in vivo. Positive effects on learning and memory have been demonstrated in various animal models and also in clinical trials. In the present study the effects of early postnatal administration of Cerebrolysin (Cere, 10 mg/ml peptides) or an enriched peptide fraction of Cere (E021, 80.6 mg/ml peptides) were investigated in young, young adult, and old adult rats. Rat pups received the drugs or saline for control on postnatal days 1–7. The animals were tested in the Morris water maze (MWM) either in the 5th week, in the 3rd or the 16th month of life for 6 consecutive days (test days 1–6), eight trials per day. In order to prevent the chance finding of the hidden platform, the rigid underwater platform was replaced by a collapsible island, resting at the bottom of the pool. The platform was raised when the animal stayed in the target area for 2 s. In the young and young adult rats both Cere and E021 treated rats showed shorter escape latencies than saline treated controls on all 6 test days. No significant differences in the swimming speed were evaluated for the young rats, although in 3-month-old drug-tested animals a moderate increase of the swimming speed was investigated. For 16-month-old animals no significant differences in either escape latencies or swimming speed was found. Summarizing, early postnatal application of Cere or E021 improved the spatial learning and memory of young rats and led to long-lasting behavioural effects at least up to 3 months after treatment.     

Cumulative biochemical effects of repeated subclinical hydrogen sulfide intoxication in mouse brain

Summary Adult female NMRI mice exposed four times to 100 ppm hydrogen sulfide vapour for 2 h at 4-day intervals showed increasing inhibition of the cerebral cytochrome oxidase activity. Cerebral RNA decreased significantly after the fourth exposure. This change was accompanied by the reduced orotic acid uptake in the RNA fraction. At the same time, 2,3-cyclic nucleotide 3-phosphohydrolase activity used as a marker for glia increased. Acetylcholine esterase activity remained unchanged. The initial exposures also caused an increase in the superoxide dismutase activity and an increase in the glutathione concentration. The latter effects were abolished in the third and fourth exposures. The present data seem to indicate that the biochemical effects of repeated subclinical hydrogen sulfide intoxications are cumulative.     

Effect of prenatal and postnatal exposure to therapeutic doses of chlorimipramine on emotionality in the rat

Prenatal administration of high doses of tricyclic antidepressants have been reported to produce teratogenic and behavioral effects in rat offspring. In the present work, behavioral abnormalities are described in offspring of rats treated with therapeutic doses of chlorimipramine (CIM) during pregnancy (CIM-P), lactation (CIM-L) and during the whole pregnancy-lactation period (CIM-PL). CIM-P treatment did not produce teratogenic effects, did not affect number or body weight of pups at birth and did not induce neonatal mortality. At 2 months of age, the CIM-P males showed a significant increase in digging and grooming (familiar environment test), a decrease in exploration (novel environment test) and a decrease in active social interactions (social behavior test). Females were more resistant than males to the prenatal CIM treatment. The results suggest increased emotionality in CIM-P pups. Some behavioral abnormalities were also observed in the tests performed at 4 months of age. CIM-L treatment had minor effects on litter behavior. CIM-PL treatment potentiated the effects of the CIM-P treatment. In the CIM-PL males, impairment of exploration of a novel environment still remained in the tests performed at 4 months of age. It is speculated that when prenatal brain development is altered by CIM, further postnatal treatment may impair compensatory processes occurring in early postnatal life.     

Unaltered insulin sensitivity during calcium channel blockade with amlodipine

Summary The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (S_I). To evaluate the effects of calcium channel blokkade on S_I, glucose homoeostasis and lipid profiles, studies were made of S_I (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal · day^–1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P<0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol·1^–1, respectively) and insulin levels (7.7 vs 7.9 U·ml^–1), S_I (10.5 vs 9.6·10^–4 × min^–1 pro U·ml^–1), serum total Tg, C and lipoprotein C fractions.The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.This work was supported in part by the Swiss National Science Foundation     

Time course of the anti-oedematous effect of O-(β-hydroxyethyl)-rutosides in healthy volunteers

Summary O-(-hydroxyethyl)-rutosides (HR) is used for the treatment of disorders of the venous and microcirculatory systems. In order to evaluate the time course of its activity, the effect of HR on a provocation model of orthostatic oedema in healthy volunteers was used. After a 2 week placebo run-in period, 16 healthy volunteers were randomized to HR (2 tablets of 500 mg/day) of placebo for a further 3 weeks, in a double-blind parallel design. Oedema was provoked by standing motionless for 1 h, with measurement of leg volume before and afterwards. The procedure was undertaken at entry to the study and then weekly during the entire 5 week period.There were no significant differences in the extent of oedema produced by the orthostatic challenge during the 2 week run-in period or in the subjects who continued on placebo (90 arbitrary units i.e. 48 ml). During the 3 week treatment with HR, however, there was a progressive reduction (–1.1, –5.9, and –7.6 arbitrary units after 1, 2, and 3 weeks, respectively) in the volume of induced oedema, which was significant after 2 and 3 weeks of treatment compared to the placebo group.