Altered regulation of the 5-HT system in the brain of MAO-A knock-out mice

Genetic deficiency of monoamine oxidase-A (MAO-A) induces major alterations of mood and behaviour in human. Because serotonin (5-HT) is involved in mood regulation, and MAO-A is responsible for the catabolism of 5-HT, we investigated 5-HT mechanisms in knock-out mice (2-month-old) lacking MAO-A, using microdialysis, electrophysiological, autoradiographic and molecular biology approaches. Compared to paired wild-type mice, basal extracellular 5-HT levels were increased in ventral hippocampus (+202%), frontal cortex (+96%) and dorsal raphe nucleus (DRN, +147%) of MAO-A mutant mice. Conversely, spontaneous firing rate of 5-HT neurons in the DRN (recorded under chloral hydrate anaesthesia) was approximately 40% lower in mutants. Acute 5-HT reuptake blockade by citalopram (0.2 and 0.8 mg/kg i.v.) produced a much larger increase in extracellular 5-HT levels (by approximately 4 fold) and decrease in DRN neuronal firing (with a approximately 4.5 fold decrease in the drug's ED50) in MAO-A knock-out mice, which expressed lower levels of the 5-HT transporter throughout the brain (-13 to -34% compared to wild-type levels). The potency of the 5-HT1A agonist 8-OH-DPAT to produce hypothermia and to reduce the firing of DRN serotoninergic neurons was significantly less in the mutants, indicating a desensitization of 5-HT1A autoreceptors. This was associated with a decreased autoradiographic labelling of these receptors (-27%) in the DRN. Altogether, these data indicate that, in MAO-A knock-out mice, the enhancement of extracellular 5-HT levels induces a down-regulation of the 5-HT transporter, and a desensitization of 5-HT1A autoreceptors which allows the maintenance of tonic activity of 5-HT neurons in the DRN.     

Vestibular functions in patients with tinnitus only

Objective: Tinnitus is the perception of sound in the ears or head without any external or internal acoustic stimulation, and it is usually associated with hearing loss. In addition, it has been reported that there is a relationship between vestibular problems and sensorineural hearing loss. The aim of this study was to evaluate the vestibular function in patients with tinnitus without hearing loss.

Methods: A total of 32 patients who complained only of tinnitus without hearing loss and 30 control subjects without tinnitus or hearing loss were included in this study. Oculomotor and caloric tests were performed on all subjects with videonystagmography. The tinnitus handicap inventory questionnaire, side and duration of tinnitus were recorded in all patients.

Results: The caloric test was abnormal in 13 of 32 (40.6%) patients in the tinnitus group and was normal in all of the control group. Abnormal caloric responses in patients with severe tinnitus were more frequent than in patients with mild or moderate tinnitus. There was a statistically significant difference in the optokinetic gain values between the tinnitus and control groups.

Conclusion: A relationship between tinnitus and abnormal caloric responses was determined. Tinnitus may be the first symptom of vestibular dysfunction.     

Cholangiographic features in fibrosis and cirrhosis of the liver

The cholangiographic features of intrahepatic bile ducts associated with cirrhosis or fibrosis are not well known. In order to achieve a radiological—pathological correlation, we studied nine livers with fibrosis or cirrhosis excised at autopsy. Cholangiograms were obtained within 24 hr after death from the nonfixed liver and multiple tissues samples were taken for histologic examination. Radiological data were interpreted by two independent investigators blinded to the clinical and histological findings. Cirrhosis (alcoholic in 4, posthepatitis in two) was observed in six livers, fibrosis (alcoholic in 2, posthepatitis in one) in three. No liver with fibrosis had cholangiographic abnormalities. In contrast, cholangiography of all livers with cirrhosis was abnormal. Abnormalities were a diminished arborization, a decrease of the distal opacification, an irregularity of caliber, and a tortuous course of the bile ducts. Histological study showed that the irregular and tortuous course were due to compression of the bile ducts by regenerative nodules. Furthermore, a thick fibrosis was organized around the bile ducts. In conclusion, fibrosis alone was not associated with cholangiographic abnormalities. In cirrhotic livers, intrahepatic bile ducts showed an irregular and tortuous course, a diminished arborization and a decrease of the distal opacification. These abnormalities were secondary to the presence of regenerative nodules and fibrosis organized around the bile ducts.     

Destruction of noradrenergic cell bodies by intracerebral 6-hydroxydopamine in the newborn rat

Intracerebral injections of 6-hydroxydopamine directly in the nucleus locus coeruleus were performed in 4-day-old rats. The effects of such treatment on the subsequent development of this nucleus were analyzed and compared to those obtained in vehicle-injected age-paired controls. The 3 histological techniques used (Nissl, Glenner reaction, and histochemical fluorescence) indicated in the experimental group a progressive disappearance of the coerulean perikarya within 7 days postinjection. This lesion was permanent and did not induce any noradrenergic sprouting.     

Sleep of preterm neonates under developmental care or regular environmental conditions

Sleep is the main behavioral state of the premature infant. In adult intensive care units, sleep deprivation has been reported as one of the major stressors. Developmental care (DC) aims to decrease stressful events in neonatal intensive care unit and support well-being. AIM: To assess whether DC is accompanied by changes in sleep in preterm neonates. METHODS: A prospective cross-over study included 33 preterm neonates [mean (S.D.): gestational age: 29.3 (1.8) weeks; birth weight: 1245 (336) g]. Polysomnography was performed in two randomly ordered 3-h periods with and without DC. A blinded electrophysiologist analyzed sleep. The total sleep time (TST) was the primary outcome, duration of active (AS), quiet (QS) and indeterminate sleep, and latency before sleep were the secondary outcomes. Non-parametric Wilcoxon tests and ANOVA were used. RESULTS: In DC condition vs. control: TST increased [in minutes, mean (S.E.M.): 156.2 (2.9) vs. 139.2 (4.6), p=0.002], with increase in AS [86.6 (3.7) vs. 77.0 (4.2), p=0.024] and in QS [47.1 (4.1) vs. 36.9 (4.2), p=0.015], and sleeping latency decreased (2.1 (0.7) vs. 10.5 (2.0), p=0.0005]. CONCLUSION: DC promoted sleep in our study. The impact of DC on the neuro-behavioral outcome needs futures studies.     

Decrease in left ventricular ejection time on digital arterial waveform during simulated hypovolemia in normal humans

BACKGROUND: Left ventricular ejection time (LVET) measured in central arteries is modified during hypovolemia. We compared modifications of the pulse wave in a central artery (carotid) and in a peripheral artery (digital) during central hypovolemia induced by lower body negative pressure (LBNP) in conscious volunteers. METHODS: Hypovolemia was simulated with progressive LBNP (baseline, -10, -20, and -30 mm Hg) in nine young healthy volunteers. The carotid arterial pressure waveform was recorded using a Millar tonometric method. The digital pulse wave was measured with a volume-clamp method (Finapres) and the stroke volume with a thoracic impedance method (Biomed). RESULTS: Mean arterial pressure did not change during LBNP. Compared with baseline values, heart rate increased significantly at the -30 mm Hg level (68 +/- 13 beats/min vs. 59 +/- 11 beats/min), and stroke volume decreased as soon as -10 mm Hg was achieved (113 +/- 41 mL vs. 127 +/- 35 mL). Both carotid and digital LVET decreased significantly at the -10 mm Hg level (337 +/- 26 and 339 +/- 24 ms vs. 360 +/- 35 and 361 +/- 24 ms, respectively). CONCLUSION: Peripheral LVET could reflect variation of central LVET during LBNP and be a reliable noninvasive parameter for monitoring hypovolemia.     

New methods and software tools for high throughput CDR3 spectratyping. Application to T lymphocyte repertoire modifications during experimental malaria

Immune repertoires of T or B cells are very often studied by Complementary Determining Region 3 (CDR3) spectratyping. However, data obtained with this method is usually subject to a biased eye analysis. We developed recently the ISEApeaks software package to retrieve and handle peak data from automated sequencers, from which CDR3 spectratype data is obtained. We describe a general strategy for CDR3 spectratype analysis based on two new specific modules and multivariate statistics. The first module addresses the crucial problem of peak smoothing. The second is a toolbox for the analysis of CDR3 spectratypes, which includes perturbation computation, recurrent peak finding, expansion assessment and datamining. To illustrate our approach, we assessed the complex TCRB repertoire modifications induced by Plasmodium berghei ANKA (PbA) infection. This global and exhaustive repertoire analysis approach is of general interest for T- and B-lymphocyte repertoire studies and is currently used in human cohorts in various pathologies and during clinical trials.     

Trisomie 21 et autisme : double diagnostic, évaluation et intervention

Autism is recognized as an additional diagnosis possible in people with Down syndrome. This pathology is still rarely detected and treated in this population in France. This article is a review of the English literature and of studies led during the last fifteen years. Studies have identified the expression of autism clinical signs in children with Down syndrome and the sensitivity and specificity of diagnostic instruments for autism in this population despite their cognitive impairments. This paper emphasizes authors’ recommendations about intervention taking into account the dual diagnosis: they encourage the identification of autism as well as early and appropriate intervention for those children whose needs differ from their peers without comorbid disorder. These results show the need to educate professionals about the importance of the detection of autism in children with Down syndrome, and the prevention that could follow.