SYNDROME DE LA FENTE MEDIANE A PROPOS D’UN CAS

The median cleft syndrome is a complex facial dysmorphism. it may be associated with other malformations incompatible to life. Prenatal diagnosis is of major interest to prepare parents and to accept the child's disability. Through an observation collected in pediatric ophthalmology department, we present the characteristics of this disease. This is an infant of 5 months, the sole of his family,from a non-consanguineous marriage and consults for a facial dysmorphism. The ophthalmology test note a cyst dermoid bilateral interest blade, the conjunctiva, 2 / 3 of the cornea uncomfortable viewing eyes. The CT cranio-orbital showed a hypoplastic orbits with cerebral atrophy. The heart-ultrasound showed a perished ventricular , restrictive intercomminication. The caryotype study was normal. The ophthalmological treatement consisted to a surgical cure of both dermoid cysts. We discuss the clinical et paraclinical, etiopathogenic aspects of the slots medians and we stress the importance of antenatal diagnosis of this condition.Le syndrome de la fente médiane est une dysmorphie faciale complexe pouvant rentrer dans un cadre polymalformatif incompatible avec la vie. Le diagnostic anténatal revêt un intérêt majeur pour préparer les parents et l’entourage à l’accueil de l’enfant et son handicap. À travers une observation colligée au service d’ophtalmologie pédiatrique, nous présentons les caractéristiques de cette affection. Il s’agit d’un nourrisson de 5 mois unique de sa famille, issu d’un mariage non consanguin et consultant pour une dysmorphie faciale. L’examen ophtalmologique a noté un kyste dermoïde bilatérale intéressant le limbe, la conjonctive, les 2/3 de la cornée gênant la visualisation des yeux. Le bilan malformatif a montré à la TDM cranio-orbitaire une hypoplasie des orbites avec atrophie cérébrale. L’écho-coeur a montré une communication inter ventriculaire péri membraneuse restrictive. L’étude du caryotype était normale. La prise en charge ophtalmologique a consisté en une cure chirurgicale des deux kystes dermoïdes. Nous discutons les aspects cliniques, para cliniques, étiopathogéniques des fentes médianes et nous insistons sur l’importance du diagnostic anténatale de cette affection

Manifestations ophtalmologiques du lupus chez l’enfant

Le lupus  à début pédiatrique est une maladie souvent sévère, dont la morbidité à long terme est importante. Ses manifestations ophtalmologiques sont variées et peuvent être révélatrices.  Elles sont  représentées par les nodules cotonneux avec ou sans hémorragies intra rétiniennes. Les auteurs rapportent l'observation d'un enfant  ayant un lupus érythémateux disséminé qui a présenté une vascularite  rétinienne

Inter-α-Inhibitor Blocks Epithelial Sodium Channel Activation and Decreases Nasal Potential Differences in ΔF508 Mice

Increased activity of lung epithelial sodium channels (ENaCs) contributes to the pathophysiology of cystic fibrosis (CF) by increasing the rate of epithelial lining fluid reabsorption. Inter-α-inhibitor (IαI), a serum protease inhibitor, may decrease ENaC activity by preventing its cleavage by serine proteases. High concentrations of IαI were detected in the bronchoalveolar lavage fluid (BALF) of children with CF and lower airway diseases. IαI decreased amiloride-sensitive (IENaC) but not cAMP-activated Cl− currents across confluent monolayers of rat ATII, and mouse nasal epithelial cells grew in primary culture by 45 and 25%, respectively. Changes in IENaC by IαI in ATII cells were accompanied by increased levels of uncleaved (immature) surface α-ENaC. IαI increased airway surface liquid depth overlying murine nasal epithelial cells to the same extent as amiloride, consistent with ENaC inhibition. Incubation of lung slices from C57BL/6, those lacking phenylalanine at position 508 (∆F508), or CF transmembrane conductance regulator knockout mice with IαI for 3 hours decreased the open probability of their ENaC channels by 50%. ∆F508 mice had considerably higher levels the amiloride-sensitive fractions of ENaC nasal potential difference (ENaC-NPD) than wild-type littermates and only background levels of IαI in their BALF. A single intranasal instillation of IαI decreased their ENaC-NPD 24 hours later by 25%. In conclusion, we show that IαI is present in the BALF of children with CF, is an effective inhibitor of ENaC proteolysis, and decreases ENaC activity in lung epithelial cells of ∆F508 mice

K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport

<p>Abstract</p> <p>Background</p> <p>Lung epithelial Na⁺channels (ENaC) are regulated by cell Ca²⁺signal, which may contribute to calcium antagonist-induced noncardiogenic lung edema. Although K⁺channel modulators regulate ENaC activity in normal lungs, the therapeutical relevance and the underlying mechanisms have not been completely explored. We hypothesized that K⁺channel openers may restore calcium channel blocker-inhibited alveolar fluid clearance (AFC) by up-regulating both apical and basolateral ion transport.</p> <p>Methods</p> <p>Verapamil-induced depression of heterologously expressed human αβγ ENaC in <it>Xenopus </it>oocytes, apical and basolateral ion transport in monolayers of human lung epithelial cells (H441), and <it>in vivo </it>alveolar fluid clearance were measured, respectively, using the two-electrode voltage clamp, Ussing chamber, and BSA protein assays. Ca²⁺signal in H441 cells was analyzed using Fluo 4AM.</p> <p>Results</p> <p>The rate of <it>in vivo </it>AFC was reduced significantly (40.6 ± 6.3% of control, <it>P </it>< 0.05, n = 12) in mice intratracheally administrated verapamil. K_Ca3.1(1-EBIO) and K_ATP(minoxidil) channel openers significantly recovered AFC. In addition to short-circuit current (Isc) in intact H441 monolayers, both apical and basolateral Isc levels were reduced by verapamil in permeabilized monolayers. Moreover, verapamil significantly altered Ca²⁺signal evoked by ionomycin in H441 cells. Depletion of cytosolic Ca²⁺in αβγ ENaC-expressing oocytes completely abolished verapamil-induced inhibition. Intriguingly, K_V(pyrithione-Na), K _Ca3.1(1-EBIO), and K_ATP(minoxidil) channel openers almost completely restored the verapamil-induced decrease in Isc levels by diversely up-regulating apical and basolateral Na⁺and K⁺transport pathways.</p> <p>Conclusions</p> <p>Our observations demonstrate that K⁺channel openers are capable of rescuing reduced vectorial Na⁺transport across lung epithelial cells with impaired Ca²⁺signal.</p

Lipopolysaccharide modifies amiloride-sensitive Na+ transport processes across human airway cells: role of mitogen-activated protein kinases ERK 1/2 and 5

Bacterial lipopolysaccharides (LPS) are potent inducers of proinflammatory signaling pathways via the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK), causing changes in the processes that control lung fluid homeostasis and contributing to the pathogenesis of lung disease. In human H441 airway epithelial cells, incubation of cells with 15 µg ml−1 LPS caused a significant reduction in amiloride-sensitive Isc from 15 ± 2 to 8 ± 2 µA cm−2 (p = 0.01, n = 13) and a shift in IC50 amiloride of currents from 6.8 × 10−7 to 6.4 × 10−6 M. This effect was associated with a decrease in the activity of 5 pS, highly Na+ selective, amiloride-sensitive <1 µM channels (HSC) and an increase in the activity of ∼18 pS, nonselective, amiloride-sensitive >10 µM cation channels (NSC) in the apical membrane. LPS decreased αENaC mRNA and protein abundance, inferring that LPS inhibited αENaC gene expression. This correlated with the decrease in HSC activity, indicating that these channels, but not NSCs, were comprised of at least αENaC protein. LPS increased NF-κB DNA binding activity and phosphorylation of extracellular signal-related kinase (ERK)1/2, but decreased phosphorylation of ERK5 in H441 cells. Pretreatment of monolayers with PD98059 (20 µM) inhibited ERK1/2 phosphorylation, promoted phosphorylation of ERK5, increased αENaC protein abundance, and reversed the effect of LPS on Isc and the shift in amiloride sensitivity. Inhibitors of NF-κB activation were without effect. Taken together, our data indicate that LPS acts via ERK signaling pathways to decrease αENaC transcription, reducing HSC/ENaC channel abundance, activity, and transepithelial Na+ transport in H441 airway epithelial cells