[Electrophysiologic tests and benzodiazepine hypnosis]. / Tests électrophysiologiques et hypnose aux benzodiazépines.

The effects of a pure benzodiazepine antagonist (Flumazenil) on the responses R1 and R2 of the blink reflex, psychomotor tests, and Event Related Potentials (ERP), in six healthy volunteers sedated with Midazolam have been compared. Measurements were made during each of four successive phases. Phase 0 corresponded to control recordings. Midazolam was administered rapidly during phase 1 and slowly during phase 2. Phase 3 corresponded to spontaneous waking once the administration of Midazolam had been stopped. Flumazenil was administered during phase 2. As the subjects fell asleep, R1 and R2 were the last parameters to disappear. Under the influence of Flumazenil, R1 was the first to reappear, while R2 did not recur until complete waking, and the other tests were unpracticable. During phase 3, R1 reappeared before R2 once more, the psychomotor test responses and ERP returning only later. The modifications of both R1 and R2 of the blink reflex are a good criterion of the presence of BZD in a toxic coma and a good test to indicate the depth of a coma or a sedation with BZD, whilst ERP, since they require the cooperation of the patient, are a test of vigilance and not of awakening.

Lack of activity of amphotericin B in systemic murine fusarial infection.

Systemic fusarial infections have emerged as a significant cause of mortality in cancer patients. Yet, little is known about the management of these infections. The in vivo antifungal activity of amphotericin B in CF1 mice with disseminated fusarial infections was studied. Two pathogenic strains of Fusarium solani were used. Intraperitoneal administration of amphotericin B in daily doses of 0.5, 1, and 2 mg/kg for less than or equal to 10 days did not prolong survival of treated animals. Clearance of F. solani from kidneys was similar in mice treated with 1 mg/kg per day of amphotericin B and in untreated animals. These results are in agreement with the known in vitro and in vivo resistance of Fusarium species to amphotericin B.

Biochemical, immunocytochemical and morphological evidence for an interaction between thyroid hormone and nerve growth factor in the developing cerebellum of normal and hypothyroid rats.

The effects of treatment with L-thyroxine (T4), 2.5 S nerve growth factor (NGF), monoclonal anti-NGF and monoclonal anti-NGF receptor antibodies, separately or together, on the two main processes of cerebellar histogenesis, the disappearance of the external granular layer (egl) and Purkinje cell (PC) morphogenesis, were studied in 10-day-old (1 day after the last injection) and 15-day-old normal and hypothyroid rats. The results provide the following information. (1) Anti-NGF antibodies given to normal rats alter more markedly the growth of PC soma and dendrite than the developmental pattern of egl. In contrast, anti-NGF receptor antibodies mainly delay the disappearance of egl, with minor changes in PC morphogenesis. This is the first evidence for a physiological role of NGF in neuronal maturation in both pre- and postmigratory phases. (2) The delays in the disappearance of egl and hypotrophy of PC due to hypothyroidism are greater than those induced in normal rats by anti-NGF antibodies, and T4 therapy in hypothyroid rats is more effective than that with NGF. The effects of combined T4/NGF treatment on PC size (including soma and dendrite) were approximately the sum of individual effects, with no apparent positive cooperation. Moreover, the effects of NGF treatment, but not those of T4, disappear over the long term. (3) Thyroid deficiency strongly reduces NGF receptor immunoreactivity. Anti-NGF antibodies given to thyroid-deficient rats partly counteract T4 therapy on the cerebellar growth and cortex layering, whereas they potentiate the action of the T4 on the growth of PC nuclei. The PC somas of thyroid-deficient rats assume a normal shape only after T4/NGF treatment. The perisomatic processes of immature PC in thyroid-deficient rats disappear after T4 therapy whereas they grow after NGF treatment. These results strongly suggest that NGF is complementary to thyroid hormone, and that the T4 action is partly mediated and regulated by NGF. Finally, thyroid hormone appears to have a long-term permissive role, while NGF may be a local and short-term limiting neurotrophic factor. Such a balance is essential for ensuring a normal time course of cerebellar histogenesis.

An interaction between thyroid hormone and nerve growth factor promotes the development of hippocampus, olfactory bulbs and cerebellum: a comparative biochemical study of normal and hypothyroid rats.

The effects of treatment with L-thyroxine (T4;20 ng/g body weight, given subcutaneously on days 1, 3, 5, 7 and 9), 2.5 S nerve growth factor (NGF; 2 ng/mg brain weight, given intracerebroventricularly on days 1, 3, 5, 7 and 9), monoclonal anti-NGF (2 ng/mg wet weight, given intracerebroventricularly on days 1, 3, 5, 7 and 9), and monoclonal anti-NGF receptor (192 IgG; 2 ng/mg wet weight, injected daily from day 1 to day 9) antibodies, separately or together, were studied on the biochemical development of hippocampal formation, olfactory bulbs and cerebellum in 10-day-old and 15-day-old normal and hypothyroid rats. The results provide the following information: (1) CNS structures other than the basal forebrain are sensitive to NGF during early development. (2) Both normal and hypothyroid rats are more sensitive to NGF deprivation than NGF supplementation. (3) The effects of anti-NGF antibodies in normal rats are similar to those induced by anti-NGFr antibodies. (4) NGF alone had little or no effect, but interacts with T4 in promoting cell maturation, especially in hypothyroid rats. (5) Hypothyroid rats are more sensitive to T4 and to T4 plus NGF than are normal ones. (6) The synergistic action of both trophic factors, but not that of T4, tend to disappear at long term in hypothyroid rats. (7) The differential sensitivity of the brain areas to T4, NGF, or both trophic factors correlates with their cell acquisition rate, especially in hypothyroid rats. (8) T4 and NGF together act more markedly (but not exclusively) on the cholinergic structures in both normal and hypothyroid rats. (9) RNA appears to be very sensitive to NGF, especially in hypothyroid rats. In close correlation with preliminary morphological observations, the results clearly demonstrate that an interaction between T4 and NGF regulates the ontogeny of a number of neuronal structures in CNS independently of their neurotransmitter phenotype, but with a regional specificity. The possibilities of accounting for this interaction, in particular the major role of thyroxine, are discussed.