Pharmacokinetic interaction between itraconazole and ceftriaxone in Yucatan miniature pigs.

Since ceftriaxone and itraconazole are highly protein bound, are excreted via a biliary pathway, and are in vitro modulators of the efflux pump P glycoprotein, a pharmacokinetic interaction between these antimicrobial agents can be hypothesized. Therefore, we evaluated the pharmacokinetics of itraconazole and ceftriaxone alone and in combination in a chronic model of catheterized miniature pigs. Itraconazole does not influence ceftriaxone kinetic behavior. The mean areas under the concentration-time curve (AUC) were 152.2 microg x h/ml (standard deviation [SD], 22.5) and 129.2 microg x h/ml (SD, 41.2) and the terminal half-lives were 1.1 h (SD, 0.3) and 0.9 h (SD, 0.2) when ceftriaxone was given alone and combined with itraconazole, respectively. Regarding itraconazole kinetics, ceftriaxone was shown to alter the disposition of the triazole. Contrary to what was expected, the AUC (from 0 to 8 h) decreased from 139.3 ng h/ml with itraconazole alone to 122.7 ng h/ml with itraconazole and ceftriaxone combined in pig 1, from 398.5 to 315.7 ng x h/ml in pig 2, and from 979.6 to 716.6 ng x h/ml in pig 3 (P of <0.01 by analysis of variance).

Ventromedial hypothalamic lesions prevent the fasting-induced changes in day-night pattern of locomotor activity.

The time-course of day-night organization of running wheel activity during prolonged fasting was studied in rats, with or without electrolytic lesions in the ventromedial hypothalamus (VMH). For each individual, dates were referenced to the metabolic transition from lipid to protein utilization in late fasting; this was estimated by daily weighing. In fasted sham-operated controls, daytime activity increased progressively over the fast. This fasting-induced rise in diurnal activity was not due to daily handling, since it was observed also in non-handled (fasted) controls. The pattern of the increase in sham-operated rats differed between 2-hour periods (8-10 h to 18-20 h). The distribution of nocturnal activity was also modified during food deprivation: nocturnal activity in late fasting increased in the 20-22 h period and concomitantly decreased in the two 4-6 h and 6-8 h periods. By contrast, VMH lesions markedly limited and delayed the rise in diurnal running activity, irrespective of the 2-hour period. They prevented any significant change in nocturnal activity pattern over the fast. In fasted sham-operated rats, the data may be interpreted as a phase-advance of the nocturnal pattern of locomotor activity, concomitant with the increase of activity during daytime. These changes were suppressed by the VMH lesions. This suggests that the fasting-induced changes in the day-night pattern of locomotor activity are centrally mediated by a neuronal circuit involving the ventromedial hypothalamus.

[Study by questionnaire of the influence of weather conditions, particularly fog, on the symptomatology of asthmatic subjects]. / Etude par questionnaire de i'influence des conditions météorologiques, en particulier du brouillard sur la symptomatologie des sujets asthmatiques.

The role of fog in the symptomatology in asthmatic subjects has been assessed by a questionnaire concerning respiratory complaints linked to meteorological conditions and to non-specific irritant factors. In a population of 121 asthmatics (59 men and 62 women) 74.4% complained that fog was a factor aggravating their symptoms while only 3% of a group of 30 non-asthmatic subjects expressed discomfort during episodes of fog. The chemical analysis of fog during 32 episodes of local fog (pH, chloride, nitrate, sulphate, sodium, ammonia, potassium, magnesium, calcium) has shown a greater concentration of pollutants and greater acidity in the smaller particles (2-6 microns) which are able to penetrate the bronchial tree. This acidity could explain the role of fog in respiratory physiology. Certain authors have suggested that the aggravation of respiratory symptoms observed during peaks of pollution could be induced by aerosols containing sulphuric acid while others have described effects on respiratory function at the time of exposure to acid aerosols in asthmatic subjects but the results of the different studies have not all been concordant. Putting aside the role of the susceptible individual, other factors may intervene at the time inhalation of pollutants, notably the ambient humidity, the neutralising effect of endogenous ammonia and the synergystic effect between acid aerosols and atmospheric pollutants.

[Childhood psychoses and organic pathology: results of a study of 144 cases]. / Psychoses infantiles et pathologie organique: résultats d'une étude sur 144 cas.

The records of 144 patients of Child Psychiatry Units of Alsace (France), with childhood psychosis (CP) or pervasive developmental disorders (PDD) have been systematically screened for previous or associated pathological events. Half of the children studied have been or are still affected by severe somatic disorders, but none of the diagnostic subcategories (referring to DSM III or CFTMEA) appeared significantly more frequently affected. In our population, the severity of organic disorders was positively correlated with: the age of the mother: more severe cases were reported when the mother was younger than 20 or older than 40 at the moment of childbirth; pathological events during pregnancy; early mother-child separation during the first year of life. The most frequent associated disorders however (neonatal pathology 45% of the cases, epilepsy 17% of the cases, neurological or neurosensorial pathology 15% of the cases) were associated neither with a specific diagnostic nor with a clinical and social specific pattern. The only statistically significant correlation was found between neurological pathology and a relatively low level of cognitive and social functioning. All these results were confirmed by multivariate statistical analysis. A main component analysis integrating all quantified data concerning organic pathology was performed: it emphasizes the independence of the different pathological events reported. The factorial analysis including the clinical, diagnostical and somatic event-related data failed to show any statistical profile associating functional features of the children with any particular previous or existing somatic disorders. Our results suggest that a history of organic pathological events is frequent not only in autistic disorders but in any kind of PDD or early CP - associated with moderate to severe mental retardation, in most cases of our study. However, this does not demonstrate that this type of pathological events constitute the direct and unique cause of PDD and CP: the concept of the aetiology of these severe diseases must take account of other factors - such as relational disruption -, also frequently seen in these children.

Search for rhythmicity during hibernation in the European hamster.

Temporal patterns of hibernation were studied by continuous monitoring of body temperature by radiotelemetry over 6 months in European hamsters, Cricetus cricetus, at constant temperature and photoperiod. Entrances into hibernation occurred mostly at the end of the night (0000-0800 hours), while arousals were randomly distributed between day and night. This is at variance with a control of bout duration by a clock with a period of 24 h. Consequently, the timing of entrances implies a phase-resetting of the circadian clock on each arousal. Persistence of circadian rhythmicity with a period different from 24 h during deep hibernation was investigated examining whether the durations of torpor bouts were integer multiples of a constant period. A non-parametric version of the classical contingency test of periodicity was developed for this purpose. Periods ranging from 21 to 29 h were tested. Nine animals out of ten showed at least one significant period in this range (P < 0.01), either below 24 h (21.8 +/- 0.5 h, n = 4) or above (27.3 +/- 0.5 h, n = 7). However, we have found a theoretical model of bout durations for which the contingency test of periodicity sometimes gives false significant results. This indicates that the power of the test is weak. With this reservation our results suggest that a circadian oscillator controls the duration of a bout of hibernation, which would occur after an integer, but variable and possibly temperature-dependent number of cycles.

Electron microscopic study of yeast RNA polymerase A: analysis of single molecular images.

The structural features of the yeast DNA-dependent RNA polymerase A (I) were examined by Scanning Transmission Electron Microscopy. The enzyme was absorbed in its monomeric form and negatively stained prior to digital image acquisition at low dose. The signal to noise ratio of single particle images was improved through averaging of a large number of previously aligned and partitioned images. Six classes of images were obtained reproducibly which corresponded to different projections of the enzyme. The enzyme structure was characterized by its presence of two curved arms which defined a longitudinal cleft. By analogy with the Escherichia coli enzyme, these arms could correspond to the two large subunits A135 and A190.