[Congenital mucocele of the ventral face of the tongue]. / Mucocèle congénitale de la face ventrale de la langue.

BACKGROUND: Congenital cystic lesions of the oral cavity are an extremely rare occurrence. Their prenatal diagnosis is essential since they can impede respiratory and swallowing functions. We describe a case that was detected prenatally and discuss its management. CASE REPORT: A 21-year-old primigravida patient who was 23 weeks pregnant was referred to our obstetrics and gynecology center after fetal ultrasonography showed a cystic lesion of the oral cavity. She had no family history of any congenital anomalies. Ultrasonography showed a male fetus with an anechoic mass measuring 21×11 mm encompassing the entire oral cavity, evoking either a mucocele or a cystic hygroma. Magnetic resonance imaging (MRI) showed a fetus with a wide-open mouth, due to a well-demarcated protruding cystic mass with no solid component, suggestive of a mucocele. A prenatal sonographically guided percutaneous needle aspiration of mucous fluid was performed at 33 gestational weeks. Although the mucocele decreased significantly in size, it nevertheless continued to expand progressively. After an uncomplicated pregnancy, the patient had spontaneous onset of labor at 39 weeks of gestation. An iterative aspiration was performed in the same manner in utero, resulting in a complete collapse of the mucocele. If needed, intubation could be considered. A 3030-g male was born by vaginal delivery, without respiratory distress. Clinical examination showed the extremely opened mouth and confirmed the presence of a large cystic mass approximately 4 cm in diameter, of sublingual origin and encompassing the entire oral cavity. The continuous protrusion of the tongue was responsible for the infant's inability to close the mouth and be breastfed. After insertion of a feeding tube, the newborn had maxillofacial surgery consisting in marsupialization of the cyst at 2 days of age. The mucocele decreased in size and the postoperative course was uneventful. No recurrence was observed at 6 months' follow-up. DISCUSSION AND CONCLUSION: Congenital mucoceles of the tongue are very rare benign lesions of the oral cavity, resulting from extravasation or retention of mucus from minor salivary glands. Their prevalence is unknown and, to our knowledge, less than ten cases of prenatal diagnosis have been previously reported. Such cystic lesions can cause respiratory distress and swallowing disorders in newborns. They are usually suspected on ultrasonography. MRI highlights the nature of the lesion and its locoregional connections with muscles and blood vessels. It provides a good analysis of the soft tissues and can distinguish between the muscles of the tongue and the pathologic mass. However, the use of CT has been reported when the diagnosis was made after childbirth or in adulthood. Given the risks of interference of the lesion with respiratory and swallowing functions, intrauterine decompression of the mucocele can be an option to prevent respiratory distress at birth and the need for neonatal intubation. Mucoceles provide somewhat confusing and disturbing ultrasonographic appearances, which can be stressful for the medical team and parents. Prenatal diagnosis and early surgical intervention (marsupialization, complete excision of the cyst or the salivary gland) can prevent risks of breathing distress and breastfeeding problems. Therefore, this strategy is essential to offer fast and satisfactory management of this rare but anxiety-producing congenital situation.

Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible caspase inhibitor.

Brain protection of the newborn remains a challenging priority and represents a totally unmet medical need. Pharmacological inhibition of caspases appears as a promising strategy for neuroprotection. In a translational perspective, we have developed a pentapeptide-based group II caspase inhibitor, TRP601/ORPHA133563, which reaches the brain, and inhibits caspases activation, mitochondrial release of cytochrome c, and apoptosis in vivo. Single administration of TRP601 protects newborn rodent brain against excitotoxicity, hypoxia-ischemia, and perinatal arterial stroke with a 6-h therapeutic time window, and has no adverse effects on physiological parameters. Safety pharmacology investigations, and toxicology studies in rodent and canine neonates, suggest that TRP601 is a lead compound for further drug development to treat ischemic brain damage in human newborns.

Sleep and epilepsy: A key role for nitric oxide?

PURPOSE: It has been suggested that nitric oxide (NO) is involved in sleep mechanisms and in the pathophysiology of epilepsy. Data are, however, controversial because it is not clear whether NO facilitates sleep or waking, or whether it exerts pro-or antiepileptic influences. METHODS: The question was considered through NO voltammetric measurements and electroencephalographic recordings performed in GAERS rats (Genetic Absence Epilepsy Rat from Strasbourg): an experimental model of "petit-mal" human disease. Regulatory processes of sleep and epilepsy were studied after administration of a NO synthase inhibitor [l-arginine-p-nitroanilide (l-ANA) 100 mg/kg i.p.], a NO donor (SIN-1 100 ng/2 microl i.c.v.), and the antiepileptic drugs used in clinic [valproate (VPA 200 mg/kg i.p.) and ethosuximide (ESM 100 mg/kg i.p.)]. RESULTS: In GAERS rats, spontaneous circadian organizations of spike-wave discharges and paradoxical sleep (PS) occur in an opposite way; spontaneous NO concentrations are higher during seizures than during wakefulness, slow-wave sleep, and PS, respectively. l-ANA induces a disappearance of NO peak, an epileptic induction, and a loss of PS while SIN-1 induces opposite effects. Antiepileptic effects of VPA and ESM are associated with a PS increase and a significant release of NO. CONCLUSIONS: These results indicate that NO could be, in GAERS rats, a central piece in the reciprocal inhibitory mechanisms regulating the induction of PS and spike-wave discharges. NO could prevent absence epilepsy and act as an antiepileptic substance in facilitating PS. Antiepileptic efficiency of VPA and ESM may work through their ability to release NO. A track for a new treatment of petit-mal disease in children can be envisioned.

Inhibition of lecithin cholesterol acyltransferase by phosphatidylcholine hydroperoxides.

To gain insight into the nature of the lecithin-cholesterol acyltransferase inhibitory factor(s), we separated and collected the oxidation products from oxidized lipoproteins after lipoxygenase treatment. Isolated fractions identified by chemiluminescence, as hydroperoxides of phosphatidylcholine, were found to produce a significant reduction of lecithin-cholesterol acyltransferase activity. The reaction kinetics of lecithin-cholesterol acyltransferase with reconstitued high density lipoproteins were studied in the presence of 0.6 and 1.2 microM hydroperoxides of phosphatidylcholine. No significant changes in the apparent Vmax were observed but a concentration-dependent increase in slope of the reciprocal plots and in the apparent Km values was observed with increasing hydroperoxide concentrations. These results show that the active site of lecithin-cholesterol acyltransferase is not affected by the presence of phosphatidylcholine hydroperoxides. Nevertheless, hydroperoxides of phosphatidylcholine altered the reactivity of lecithin-cholesterol acyltransferase for reconstitued high density lipoproteins suggesting either an alteration of the binding of lecithin-cholesterol acyltransferase to the reconstitued high density lipoproteins or a competitive inhibition mechanism.

The ethological method as a means for evaluating stress in children two to three years of age during a dental examination.

A dental examination could be perceived by small children as an "at-risk" situation. The behaviors observed in these children during a dental examination depend not only on the examination situation but also on other factors, such as the sex of the child or the sex of the accompanying parent. The ethological method provided a means for evaluating behavioral differences due to the sex of the child and that of the accompanying parent. Results showed that girls appeared better able to master the examination situation than did boys, regardless of the sex of the accompanying parent. The girls appeared more secure, and exhibited more exploratory behavior than did the boys. The boys, on the other hand, appeared less secure than did the girls especially when the father was the accompanying parent.

p-Chlorophenylalanine-induced alteration of somatodendritic levels of tryptophan hydroxylase within the rat mesencephalic raphe nuclei.

Tryptophan hydroxylase distribution was examined across the nuclei raphe dorsalis, medianus, and pontis of the adult rat, under basal conditions and 2 days after a single injection of p-chlorophenylalanine, an irreversible tryptophan hydroxylase inhibitor. Tryptophan hydroxylase-expressing cells were numbered in transverse sections processed for immunohistochemistry, and the area of tryptophan hydroxylase distribution was delineated in adjacent sections transferred onto nitrocellulose and processed for immunoautoradiography. Two distinct areas were visualized: an inner zone, corresponding to the area displaying tryptophan hydroxylase-immunoreactive cells (so-called somatic area), and an outer zone, here called perisomatic, devoid of perikarya yet rich in tryptophan hydroxylase-positive neuropil in the histological sections. After treatment with p-chlorophenylalanine, a significant decrease in the number of tryptophan hydroxylase-immunoreactive cells could be observed only in the rostral raphe dorsalis, particularly within its ventromedian and dorsomedian subdivisions. In all raphe nuclei, the topological reconstruction of the somatic area was not modified. Based on the densitometric measurements in the immunoautoradiographs, however, a dramatic decrease in the content, concentration, and volume of expression of tryptophan hydroxylase could be documented in the three raphe nuclei. Detailed analysis of these results led to the conclusion that (a) tryptophan hydroxylase expression is differentially regulated in different serotoninergic cell body subpopulations of the raphe, some of which are more sensitive to p-chlorophenylalanine, and (b) distribution of tryptophan hydroxylase protein is modified also in the somatodendritic area in all raphe nuclei.

Changes in steady-state levels of tryptophan hydroxylase protein in adult rat brain after neonatal 6-hydroxydopamine lesion.

A recently developed technique of immunoautoradiography on nitrocellulose transfers of serial frozen sections was used to determine tryptophan hydroxylase concentration in selected areas of the adult rat brain following neonatal 6-hydroxydopamine destruction of nigrostriatal dopamine neurons. Particular attention was paid to the neostriatum, known to be serotonin-hyperinnervated under these conditions, and to the nucleus raphe dorsalis, containing the cell bodies of origin for these nerve terminals. The hippocampus was also investigated as a territory of structurally intact serotonin innervation arising primarily from the nucleus raphe medianus. Tryptophan hydroxylase protein was measured at successive transverse levels across the entire caudorostral extent of all these regions. Similar measurements of tyrosine hydroxylase protein across the substantia nigra and the neostriatum verified the disappearance of the nigrostriatal dopamine neurons. The average tryptophan hydroxylase tissue concentration in the dorsal third of the serotonin-hyperinnervated neostriatum was up by 36% above control, i.e. significantly less than the number of its serotonin axon terminals or varicosities. This was therefore indicative of a lowering of the tryptophan hydroxylase protein content per serotonin ending. Interestingly, a tight correlation between the respective level-by-level concentrations of tryptophan hydroxylase and tyrosine hydroxylase protein in the control neostriatum allowed the prediction the tryptophan hydroxylase concentration after dopamine denervation with a serotonin hyperinnervation. Tryptophan hydroxylase concentration was also significantly reduced in both the nucleus raphe dorsalis and nucleus raphe medianus, notably at those raphe dorsalis levels known to give rise to the serotonin hyperinnervation of neostriatum. It is hypothesized that the lower steady-state level of tryptophan hydroxylase inside the terminals and cell bodies of hyperinnervating serotonin neurons was the result of a feedback inhibition of the synthesis of the enzyme by its end-product, presumably because of the increased amount of serotonin in these terminals.

Postnatal development of the tyrosine hydroxylase-containing cell population within the rat locus coeruleus: topological organization andphenotypic plasticity.

The cellular phenotypic characteristics of tyrosine hydroxylase (TH) expression have been studied within the rat locus coeruleus (LC) during postnatal development at six different stages: postnatal day 4 (PND4), PND10, PND14, PND21, PND30, and PND42. Coronal brain sections were selected at intervals of 80 microns along the caudorostral extent of the LC and processed for TH immunohistochemistry. At each anatomical level we (1) reconstructed the mean space of the LC delineated by the TH positive cell bodies, (2) enumerated the mean number of these cell bodies, and (3) determined the mean volume circumscribed by these cell bodies and their density. The topological study revealed a steady remodeling of the structure until the third week, with a progressive reducing of a ventral cellular group in the anterior LC, which was no longer observable at PND21, concomitant to the stretch of the structure toward its caudal limit. We have noted invariant and variant cellular phenotypic characteristics of TH expression. At any stage, the LC could be separated into a posterior and an anterior subregion and its total volume remained quite stable during the studied period. At PND14 and PND21, we observed a transient 33% increase in the total number of TH positive perikarya as compared to PND42. Conjoint analysis of the topological reconstruction and the density of TH positive cells suggested there were three distinct and precisely localized subsets of "quiescent" neurons. TH gene expression in these cells would have lowered between PND14 and PND21 inside two subsets and between PND21 and PND30 inside the last one. So topologically defined populations of cells could be involved in specific functions. If they have not definitively lost their TH expression capacity, they could contribute to increasing TH levels in LC occurring in response to physiological perturbations or pharmacological treatments.

Quantitative study of tyrosine hydroxylase protein levels within the somatic area of the rat locus coeruleus during postnatal development.

To date only global dosages of tyrosine hydroxylase (TH) protein have been realized in the locus coeruleus (LC) without discriminating the enzyme contained in the cell body area from the one in the surrounding neuropil. The preceding immunohistochemical study (Bezin et al., 1994) revealed a dramatic plasticity of the cellular expression of TH in the LC during the postnatal development of the rat. It was therefore necessary to develop a quantitative biochemical approach, strengthened by a great anatomical resolution, to follow the developmental evolution of TH levels exactly in the space containing the coerulean TH-immunoreactive perikarya. In the present work two biochemical parameters necessary for precisely defining the phenotypic characterization of TH expression within the rat LC have been established during the postnatal development at six different stages: postnatal day 4 (PND4), PND10, PND14, PND21, PND30, and PND42. TH tissue concentration and content were precisely determined along the caudorostral extent of the LC within the previously (Bezin et al., 1994) defined spaces delimited by the TH-containing perikarya. TH tissue concentration remained quite stable during the postnatal development. TH quantity exhibited few age-related variations with a transient peak at PND10 and followed the same evolution as the volume containing the TH-expressing perikarya. The mean cell contribution to the total quantity of TH measured in the whole LC showed important age-related fluctuations with a dramatic peak at PND10 followed by a drastic decrease until PND21.(ABSTRACT TRUNCATED AT 250 WORDS)

RU24722 induces spatially organized phenotypic plasticity in the locus coeruleus.

The plasticity of tyrosine hydroxylase (TH) expression in rat locus coeruleus (LC) was evaluated after RU24722 TH induction using, as a new parameter of characterization, the quantitative topology of LC defined by TH-positive cells. This new phenotype was spatially organized into cell subpopulations in the medial LC, dorsal and ventro-lateral to the initial perikaryal space. Reserpine and parachlorophenylalanine, which elicited a similar increase in the TH content, failed to induce a significant change in the number of TH-expressing cells. Activation of TH expression is not sufficient to reveal the existence of such a plasticity and some original but still unknown mechanism(s) of control of TH expression is affected by RU24722.

Ontogeny of tyrosine hydroxylase levels in the neuropil close to locus caeruleus.

We aimed to characterize tyrosine hydroxylase (TH) expression within the pericaerulean area (PCA) during postnatal development. Levels of TH along the caudorostral axis of the locus caeruleus (LC) showed a dramatic increase in the PCA beyond day 21. This was due to the extension of the TH-containing area, particularly organized in the ventrolateral and longitudinal directions. As dendrites of LC neurones were observed at long distances within this PCA, such an increase in TH distribution could affect functions related to the LC.

Relationship between tyrosine hydroxylase content and noradrenergic cell reactivity to piperoxane: an in vivo voltammetric approach in the rat locus coeruleus.

A previous electrochemical study showed that the increase in the tyrosine hydroxylase (TH) content of the locus coeruleus (LC) produced by RU24722 administration was associated with a relative decrease in the catecholaminergic metabolic reactivity of this nucleus to a hypotensive stimulus. Since alpha 2 receptors participate in the regulation of the activity of both LC neurons and TH, the aim of the present work was to evaluate the possible involvement of the autoinhibition mediated by alpha 2 autoreceptors in the inverse relationship between the reactivity of the LC and its TH content. Our study was divided into two successive steps: (i) the electrochemical measurement of the in vivo metabolic activation of LC cells in response to alpha 2-adrenergic receptor blockade, and (ii) the evaluation of the quantity of TH every 100 microns along the caudorostral axis in each recorded LC. The capacity of TH protein to be activated was evaluated by the measurement, using differential normal pulse voltammetry, of the in vivo variations of the extracellular 3,4-dihydroxyphenylacetic acid concentrations in response to six cumulated doses of the alpha 2-antagonist piperoxane. The corresponding dose-response curves, determined in control- and RU24722-treated rats, were expressed as a function of the quantity of TH contained either in the whole recorded LC or in the 100 microns-wide coronal interval surrounding the recording site. It was established that the slopes of the dose-response curves were significantly (P < 0.01) and inversely related to the quantity of TH at the level of the recording site. This result suggests that the negative control of the catecholaminergic metabolic reactivity in a restricted area of the LC could be directly or indirectly dependent on the level of expression of TH protein in this particular area.

Somatotopic organization of tyrosine hydroxylase expression in the rat locus coeruleus: long term effect of RU24722.

Tyrosine hydroxylase (TH) tissue concentration was determined by immunostaining of tissue sections directly transferred onto nitrocellulose membranes in the restricted region of the noradrenergic perikarya of the locus coeruleus (LC) along its postero-anterior axis. TH containing cells were systematically counted on adjacent post fixed sections stained by immunohistochemistry. The absolute quantity of TH was estimated in each section and was found to be linearly related to the number of TH immuno-positive cells found in the adjacent section. The ratio between these two parameters was thus used as an index of the cellular concentration of TH in noradrenergic cells. In the LC of control rats, the TH cellular concentration was lower (-39%) in the anterior than in the posterior half of the structure. Three days after an injection of 20 mg/kg of RU24722, an eburnamine derivative known to increase the quantity of TH in the LC, increases in quantities of TH were found in both portions of the LC. Moreover in the posterior LC the increase in the amount of TH resulted from a significant increase in the number of TH-immunopositive cells. In the anterior part, however, it was primarily the result of a significant increase in TH cellular concentration. Throughout the LC there was an increase in the cellular concentration of TH which was inversely proportional to the concentrations found in control animals. TH mRNA content was measured by a quantitative in situ hybridization in sections of both the posterior and anterior LC one day after a single injection of RU24722 at the same dose. The quantity of TH mRNA was significantly increased in both parts. The number of TH mRNA-expressing neurons also increased, especially in the anterior LC. Thus the effects at the level of TH protein and TH mRNA were strikingly parallel though increase in TH protein occurred later than the increase in the TH mRNA. These results suggest that in the rat LC: (1) there is a significant population of 'sleeping cells' in which TH expression is either inactivated or, at a low level of activation; (2) TH cellular concentration could exert a retrocontrol on its own expression in cells of the LC that contained TH and (3) TH expression appears to be regulated by different selective mechanisms in these two different subpopulations of noradrenergic cells within the LC.

Distribution of alpha-1 and alpha-2 binding sites in the rat locus coeruleus.

Precise anatomical distribution of alpha-1 and alpha-2 adrenergic binding sites has been investigated in the rat locus coeruleus (LC) using quantitative radioautography of brain sections incubated with 3H-prazosin or 3H-idazoxan. Distribution patterns of 3H-prazosin (alpha-1 sites) and 3H-idazoxan (alpha-2 sites) were heterogeneous and different along a postero-anterior axis in the LC. Comparison between distribution of alpha-2 binding sites and noradrenergic (NA) cellular density suggests that at least a fraction of these sites might be localized on NA perikarya or dendrites in this structure. Quantitative estimations of the binding parameters along this postero-anterior axis in the LC have revealed that the heterogeneous distributions of alpha-1 and alpha-2 binding sites are due not only to variations in the maximal densities of sites but also to variations in the affinities of these sites for their respective ligand.

Variation of tryptophan-5-hydroxylase concentration in the rat raphe dorsalis nucleus after p-chlorophenylalanine administration. II. Anatomical distribution of the tryptophan-5-hydroxylase protein and regional variation of its turnover rate.

Distribution of tryptophan-5-hydroxylase (TpOH)-containing cells and TpOH protein tissue concentrations were evaluated in the nucleus raphe dorsalis (NRD) of rat brain by immunocytochemistry and direct transfer onto nitrocellulose filters of unfixed adjacent brain sections. This work has demonstrated that: (1) the direct transfer onto nitrocellulose filters could be easily used for the quantitative analysis of TpOH protein distribution; (2) the origin of the TpOH in this brain nucleus was preferentially cellular; (3) classical subdivisions, qualitatively defined from morphometric and topographic observations could be precisely described in terms of cellular density, tissue and cellular concentrations and turnover of TpOH protein. Such differences could imply a physiological control of TpOH gene expression in the serotoninergic neurons.

Direct transfer into nitrocellulose and quantitative radioautographic anatomical determination of brain tyrosine hydroxylase protein concentration.

An improved quantitative immunochemical determination of brain tyrosine hydroxylase (TH) concentrations was designed using direct transfer into nitrocellulose from 20-microns thick brain sections, followed by immunodetection and quantitative radioautography in three reference brain structures (locus ceruleus, substantia nigra, and ventral tegmental area). Results obtained by this methodology were similar to those obtained after extraction and Western blotting of the TH protein in control and reserpine-treated animals. Moreover, this methodology allows the combination of high sensitivity and high anatomical resolution in the study of the distribution of pharmacological effects. The locus ceruleus exhibited a significant posteroanterior distribution of TH protein concentration in control and reserpine-treated animals.