Management of congenital dacryocystocele: report of 3 clinical cases.

This case study describes three newborns referred to our otolaryngologic service for investigating and treating a cystic dilatation of the lacrimal duct. These dilatations corresponded to unilateral or bilateral dacryocystoceles, with or without complications. The first newborn exhibited respiratory distress at birth and received early surgery and endoscopic marsupialization of intranasal and bilateral cysts. The second newborn did not show any signs of complications, and after conservative treatment for a week, the cyst spontaneously resolved. The third newborn was diagnosed in utero with ultrasonography, and the cyst resolved spontaneously during childbirth. These cases provided an opportunity to review the pathophysiology of this rare congenital lacrimal anomaly and to note responses to different therapeutic approaches. Indeed, these three cases illustrated three different management approaches, and allowed us to address the issue of prenatal diagnosis.

[When rhinosinusitis reveals a systemic disease]. / Quand la rhinosinusite révèle une pathologie systémique.

This retrospective analysis is concerned with 10 patients suffering from granulomatosis with polyangitis (GPA, Wegener's disease), who were followed up in a tertiary care Ear, Nose, and Throat (ENT) department. The inaugural events took place in the ENT field (8 patients), the lung (2 patients), the vestibule (1 patient), or the oral cavity (1 patient). The ENT manifestations during the disease evolution involved the rhinologic (osetocartilaginous--6 cases; mucosal--9 cases), the otologic (3 cases), or the laryngeal area (2 cases). Facial pain was noted in 6 cases and residual hyposmia in 5. We observed 5 cases of lung involvement, 3 cases of renal involvement, and 4 cases of ocular involvement. An aseptic meningitis was seen in 1 case and the muscles were affected in 6 cases. The average delay between symptom onset and diagnosis was 26 months. Endoscopy, imaging techniques, and determination of antineutrophil antibodies (ANCA) were used to reach the diagnosis. Sinus biopsies were contributive in 6 cases. The patients were treated with immunosuppressive drugs and/or surgery. After treatment, remission was obtained in 6 patients.

MicroRNAs tune cerebral cortical neurogenesis.

MicroRNAs (miRNAs) are non-coding RNAs that promote post-transcriptional silencing of genes involved in a wide range of developmental and pathological processes. It is estimated that most protein-coding genes harbor miRNA recognition sequences in their 3' untranslated region and are thus putative targets. While functions of miRNAs have been extensively characterized in various tissues, their multiple contributions to cerebral cortical development are just beginning to be unveiled. This review aims to outline the evidence collected to date demonstrating a role for miRNAs in cerebral corticogenesis with a particular emphasis on pathways that control the birth and maturation of functional excitatory projection neurons.

Spatiotemporal antiphase dynamics in coupled extended optical media.

Experimental evidence of spatiotemporal antiphase dynamics is given for an extended system made of two liquid crystal slices that are optically coupled by two equal amplitude counterpropagating pumping beams. Theory and experiments carried out in a transverse one-dimensional configuration show that roll patterns are generated in each slice. These rolls are spatially in-phase or antiphase for a focusing or a defocusing nonlinearity type, respectively. These in-phase or antiphase dynamics remain robust even for complex spatiotemporal regimes such as dislocation regimes.

Symmetry breaking and high-frequency periodic oscillations in mutually coupled laser diodes.

We investigate the dynamical behavior of two laser diodes coupled through mutual injection of their optical fields when placed face to face with a small separation between them. We report symmetry breaking in periodic solutions at low coupling rates. In addition, we demonstrate that at higher coupling rates both lasers exhibit very fast periodic oscillations. The system is of practical interest, since it constitutes a tunable all-optical source of microwave oscillations.

Saddle-node ghost-induced low-frequency fluctuations in an external-cavity laser diode.

We investigate numerically the low-frequency fluctuation regime in a laser diode subject to optical feedback. We demonstrate that a saddle-node ghost can induce this regime.

Bifurcation to polarization self-modulation in vertical-cavity surface-emitting lasers.

Experiments have yielded polarization self-modulation in vertical-cavity surface-emitting lasers (VCSELs) subject to a pi/2 polarization-rotating optical feedback. The phenomenon has been simulated numerically, but its bifurcation has never been explained. We show that polarization self-modulation results from a Hopf bifurcation mechanism that can be analyzed in terms of the laser feedback parameters. Our analysis predicts other bifurcations for low values of the feedback rate, which explain why more-complex time-dependent outputs have been observed as alternatives to polarization self-modulation.

Two types of synchronization in unidirectionally coupled chaotic external-cavity semiconductor lasers.

We study numerically two distant unidirectionally coupled single-mode semiconductor lasers subject to coherent optical feedback. We show that two fundamentally different types of chaotic synchronization can occur depending on the strengths of the coupling and of the feedback of the receiver laser.

Novel inhibitors of the sodium-calcium exchanger: benzene ring analogues of N-guanidino substituted amiloride derivatives.

A series of N-guanidino substituted 2,4-diamino-5-carbonylguanidine molecules related to amiloride were synthesised and evaluated for their ability to inhibit the sodium-calcium exchanger in rat insulinoma cells (RINm5F) and human platelets. Specific chemical pathways were used to prepare the benzene derivatives designed as bioisosteric analogues of the pyrazine derivatives of amiloride. Several so-called 'simplified analogues', where some substituents of amiloride were omitted or replaced, were also prepared and included in the biological evaluation. The inhibitory potency of the sodium-calcium exchanger was screened on both cell types by measuring their effect on 45Ca(2+) uptake. Among the most active compounds, N-(2-amino-5-chloro-4-nitrobenzoyl)-N'-(1-naphtylmethyl)guanidine (IC(50)=3.4 microM) was found more active than amiloride (IC(50)=690 microM) and 3,4-dichlorobenzamil (IC(50)=15.2 microM), the reference inhibitor.

Secure communication scheme using chaotic laser diodes subject to incoherent optical feedback and incoherent optical injection.

We propose a secure communication scheme based on anticipating synchronization of two chaotic laser diodes, one subject to incoherent optical feedback and the other to incoherent optical injection. This scheme does not require fine tuning of the optical frequencies of both lasers as is the case for other schemes based on chaotic laser diodes subject to coherent optical feedback and injection. Our secure communication scheme is therefore attractive for experimental investigation.

Experimental demonstration of suppression of low-frequency fluctuations and stabilization of an external-cavity laser diode.

We demonstrate experimentally all-optical stabilization of a single-mode laser diode subject to external optical feedback operating in the low-frequency fluctuations (LFF) regime, by the technique of applying a second delayed optical feedback. We interpret our results as suppression of LFF through destruction of the antimodes responsible for the LFF crises and stabilization of the laser through creation of new maximum gain modes, in agreement with recent theoretical predictions.

Suppression of low-frequency fluctuations and stabilization of a semiconductor laser subjected to optical feedback from a double cavity: theoretical results.

We demonstrate numerically that low-frequency fluctuations (LFF's) observed in a laser diode subjected to a first optical feedback with a short delay are suppressed by means of an adequate second optical feedback. The general idea of this technique is based on the observation that second feedback can suppress the antimodes that are responsible for the crises in the LFF regime. Furthermore, we observe that the second optical feedback can steer an unstable laser that is biased near threshold into a stable regime.

New dibenzazepine derivatives with disinhibitory and/or antidepressant potential: neurochemical and behavioural study in the open-field and forced swimming tests.

Original bioisosteric analogues of clozapine were evaluated for potential disinhibitory and/or antidepressant effects using the open-field test in the rat and Porsolt's forced swimming test in the mouse. Attempts to relate the behavioural results to the binding affinities for dopamine (D1, D2), serotonin (5-HT(2)) and muscarinic (M) receptors were also undertaken. In the open-field test, two main profiles were observed. The first profile corresponded to disinhibitory molecules resembling diazepam and ritanserin. The second profile corresponded to antipsychotic compounds resembling either typical (haloperidol, clothiapine) or atypical (clozapine) neuroleptics. The results obtained in the forced swimming test confirmed the neuroleptic-like activity of the second group of compounds, while two compounds of the first group (JL 3 and JL 26) showed an antidepressant-like activity, JL 3 being as active as imipramine. While it was not possible to relate the first profile to any binding interaction, a relation could be established among the second group of compounds between the typical or atypical antipsychotic behavioural profile and the 5-HT(2)/D2 ratio.

Peroxidase-catalysed oxidation of different dibenzazepine derivatives.

According to a recent hypothesis suggesting the potential role of free radical formation in the clozapine-induced agranulocytosis, we have evaluated the susceptibility to the peroxidase-mediated oxidation of different dibenzazepine analogues. On the one hand, compounds with an arylamine group such as clozapine or isoclozapine present a high reactivity in the horseradish peroxidase or myeloperoxidase systems and, on the other hand, fluperlapine, though known to induce agranulocytosis, and other dibenzothiazepine and dibenzoxazepine derivatives appear insensitive to oxidation. Consequently, among tricyclic derivatives, the way of diaryloxa- and diarylthiazepine compounds could be an alternative for the development of safer drugs such as antipsychotics.

Modulation of the clozapine structure increases its selectivity for the dopamine D4 receptor.

Clozapine has a more marked affinity for the recently cloned dopamine D4 receptor than for the dopamine D2 receptor. In the search for a selective ligand for the dopamine D4 receptor, useful as a pharmacological tool or as a potent atypical antipsychotic, a pyridobenzodiazepine derivative bioisoster of clozapine, JL 18, 8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido [2,3-b][1,4]benzodiazepine, was found to be the most dopamine D4-selective ligand belonging to the diarylazepine class. Indeed, JL 18 binds to the dopamine D4 receptor with affinity up to 25 times superior to that for the dopamine D2 receptor and presents reduced affinities for other receptors.

Pyridobenzoxazepine and pyridobenzothiazepine derivatives as potential central nervous system agents: synthesis and neurochemical study.

In order to characterize the pharmacological profile of the different chemical classes of pyridobenzazepine derivatives, a series of N-methylpiperazinopyrido[1,4]- and -[1,5]- benzoxa- and benzothiazepine derivatives were prepared. The affinities for D2, D1, 5-HT2, and cholinergic (M) receptors were measured. In comparison to dibenzazepine reference compounds, a strong decrease of the affinities was observed, less pronounced, however, for the substituted analogues. Oxazepine and thiazepine analogues like clozapine (except 8-chloro-6-(4-methylpiperazin-1-yl)-pyrido[2,3-b][1,4]benzoxazepin e (9) and 8-chloro-6-(4-methylpiperazin-1-yl)pyrido[2,3-b][1,4]- benzothiazepine (11)) were found to be inactive against apomorphine stereotypies. In the open-field test in rats, different molecules showed a high disinhibitory activity as observed with anxiolytic drugs. Moreover, 8-chloro-5-(4-methylpiperazin-1-yl)pyrido[2,3-b][1,5]benzoxazepine (14) presented a clozapine-like profile that was confirmed in the behavioral model in dogs and showed most of the behavioral characteristics described for antipsychotic drugs. Its neurochemical profile, in particular the 5-HT2/D2 ratio, was also compatible with atypical antipsychotic activity.

New pyridobenzodiazepine derivatives as potential antipsychotics: synthesis and neurochemical study.

The discovery of a new, safe, atypical antipsychotic remains an important challenge. To achieve this goal, a series of N-methylpiperazinopyrido[2,3-b] [1,4]- and -[1,5]- and -pyrido[4,3-b][1,4]- and -[1,5]- benzodiazepines were synthesized. The dopaminergic (D1, D2), serotonergic (5-HT2), and cholinergic (M) affinities, frequently remarked in the action mechanisms of antipsychotic drugs, were determined using their respective in vitro receptor binding assays. All affinities were reduced for each compound. Optimal substituents were found to be in the 2- or 8-position for the retention of affinities, while substitution at the 5-position by acyl or alkyl groups dramatically diminished binding affinities. Pyridobenzodiazepine derivatives, such as clozapine, were found to be inactive or only weakly effective against apomorphine-mediated stereotypes in rats. In an original and complex behavioral model developed in dogs and successfully used to differentiate distinct classes of psychotropic drugs and to discriminate between typical and atypical neuroleptic drugs, 8-chloro-6-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b] [1,4]benzodiazepine (9), 8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido [2,3-b][1,4]benzodiazepine (12), and 5-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b][1,5]benzodiazepine (16) showed most of the behavioral characteristics previously described for neuroleptics. Their neurochemical profiles, particularly their 5-HT2/D2 pKi ratios, were compatible with an atypical antipsychotic effect. These compounds were selected for further investigation. The proposed modulations could lead to new possibilities for the pharmacochemistry of diarylazepines.

Comparative study of typical neuroleptics, clozapine and newly synthesized clozapine-analogues: correlations between neurochemistry and behaviour.

While neuroleptic therapy with classical compounds has frequently been associated with extrapyramidal side effects, clozapine has revealed an interesting antipsychotic profile without producing any clearcut motor side effects. However, some adverse reactions remained that stimulated the search for improved antipsychotic agents. The aim of this study was to characterize the behavioural and neurochemical profiles of typical neuroleptics (chlorpromazine, haloperidol), clozapine, and four newly synthesized clozapine-analogues. Affinity for dopaminergic (D1,D2), serotonergic (5-HT(2)) and cholinergic (muscarinic) receptors were measured and the ratios of these different binding affinities were determined and correlated with the behavioural effects of the drugs in a complex temporal regulation task in the dog. The four clozapine-analogues showed most of the behavioural characteristics previously described for neuroleptics and their neurochemical profile, particularly their 5-HT(2)/D2 pKi ratio, was compatible with an atypical antipsychotic effect. Among these drugs, JL5 and JL13 showed a high degree of similarity with clozapine. Like clozapine, they did not induce catalepsy and stereotypy/hyperkinesia. Moreover, other motor effects were also reduced (ataxia, akinesia, dystony). and tremor and sialorrhea were completely absent with these two molecules.