[Lacrimal system trauma]. / Traumatologie lacrymale.

Among lacrimal system injuries, canalicular lacerations are at the top of the list. Men are more affected than women, but children are most likely to experience such trauma. The cause depends on the patient's age: in young children, there is a higher prevalence of animal bites (dogs and cats); in young adults, fights predominate, since motor vehicle accidents have become less common; in the elderly, falls are among the most frequent causes. Tetanus vaccination is required in all cases, but assessment for rabies exposure is necessary in the case of dog or cat bites. Diagnosis is very simple: it is based on examination or wound probing. Other head, facial, or ocular injuries must be excluded; for example, an injury to the globe must take precedence over a canalicular laceration. In the absence of an ocular injury, the canalicular wound should be managed surgically within 48hours under an operating microscope: identification of both severed ends of the injured canaliculus, suture of the severed canaliculus with monofilament suture, and appropriate lacrimal intubation if indicated. Other trauma to the lacrimal system, such as sharp or blunt trauma to the lacrimal sac or nasolacrimal duct, are much rarer.

Correction to: Ouabain Accelerates Collective Cell Migration Through a cSrc and ERK1/2 Sensitive Metalloproteinase Activity.

The original version of the article unfortunately contained an error in the author group. Dr. Isabel Larré was not submitted and published in the original version.

Ouabain Accelerates Collective Cell Migration Through a cSrc and ERK1/2 Sensitive Metalloproteinase Activity.

Studies made in the Madin-Darby canine kidney (MDCK) epithelial cell line showed that ouabain regulates cell adhesion and cell-adhesion-related biological processes, such as migration. Here, we demonstrated that 10 nM ouabain accelerates collective cell migration and heals wounds in cultured MDCK cell monolayers. Ouabain-induced acceleration of cell migration depends on activation of the cSrc-ERK1/2 signaling cascade, as it was inhibited by the kinase inhibitors PP2 and PD98059. Activation of the cSrc-ERK1/2 signaling cascade increased expression and activation of the extracellular matrix metalloproteinase-2 (MMP-2). Inhibition of MMP activity using the generic inhibitor GM6001 or the potent iMMP-2 inhibitor prevented the accelerative effect of ouabain. Likewise, Focal Adhesion Kinase (FAK) inhibition with the transfection of dominant negative peptide FRNK impaired the effect of ouabain. These results suggest that ouabain binding to the Na+,K+-ATPase accelerates collective migration of MDCK cells through activation of the cSrc-ERK1/2-FAK signaling cascade and promoting secretion and MMP activity.

[Adult orbital tumors]. / Tumeurs de l'orbite de l'adulte.

Orbital tumors are a rather frequent pathology. Their diagnosis and treatment may be difficult. They can be benign or malignant. All the tissues of the orbit can give rise to a tumor, resulting in their large number. Among the benign tumors, we have meningiomas and cavernous hemangiomas, and for the malignant tumors, lymphomas, metastasis, ENT tumors and lacrimal gland tumors in the adult. Usually the signs are nonspecific, with proptosis, oculomotor disturbance, inflammatory signs, pain and sometimes a mass. Imaging (CT, MRI and color Doppler ultrasound) shows the tumor, its location, extent and possible metastases. Biopsy and anatomic and cytopathologic examination confirm the type of benign or malignant tumor. Based on these three elements: clinical appearance, imaging and histology, the tumor will be treated, usually by a surgical approach according to the recommendations of a multidisciplinary tumor conference. Radiation therapy and chemotherapy may supplement the treatment.

[Lacrimal traumatology]. / Traumatologie lacrymale.

Lacrimal system injuries represent a significant part of ocular emergencies and mainly affect males of various ages including very young children. The most frequent presentations are canalicular laceration with a palpebral wound medial to the lacrimal punctum. The inferior canaliculus is the most commonly affected but bilateral injuries or injuries affecting both canaliculi can occur. The main causes are dog bites in children, scuffles in young adults and falls in elderlies. Antitetanic and antirabic measures have to be considered for open cases. The diagnosis is easily made by inspection and can be confirmed by probing. Other lesions can be associated and require proper identification, especially eyeball laceration requiring surgical repair within 6 hours. Otherwise, isolated canalicular wounds are to be repaired within 48 hours by an anastomotic suture with or without mono- or bi-canalicular silicone intubation. Other lacrimal tract injuries involving the lacrimal sac or the nasolacrimal duct are rare, commonly associated with blunt craniofacial trauma or iatrogenic after some surgical procedures.

The emergence of the concept of tight junctions and physiological regulation by ouabain.

The exchange of substances between metazoan and the environment takes place across transporting epithelia that have two fundamental differentiated features: tight junctions (TJ) and apical/basolateral polarity. Usually, reviews of the structure and function of transporting epithelia follow a historical description of major biological findings, but seldom refer to the fact that it also required fundamental theoretical changes in the physics and chemistry involved. We make a brief description of the concatenation of both types of achievements, in which it becomes clear that the major source of conflicts was the enzyme Na(+),K(+)-ATPase (also referred to as "the pump"), because of its intrinsic mechanisms and its asymmetric expression on one side of epithelial cells only (polarity). This enzyme is also the receptor of the newly recognized hormone ouabain, whose chief function is to modulate cell contacts, such as TJs, several types of cell-cell contacts participating in polarization (as gauged through ciliogenesis).

The Na+-K+-ATPase as self-adhesion molecule and hormone receptor.

Thanks to the homeostasis of the internal milieu, metazoan cells can enormously simplify their housekeeping efforts and engage instead in differentiation and multiple forms of organization (tissues, organs, systems) that enable them to produce an astonishing diversity of mammals. The stability of the internal milieu despite drastic variations of the external environment (air, fresh or seawater, gastrointestinal fluids, glomerular filtrate, bile) is due to transporting epithelia that can adjust their specific permeability to H(2)O, H(+), Na(+), K(+), Ca(2+), and Cl(-) over several orders of magnitude and exchange substances with the outer milieu with exquisite precision. This exchange is due to the polarized expression of membrane proteins, among them Na(+)-K(+)-ATPase, an oligomeric enzyme that uses chemical energy from ATP molecules to translocate ions across the plasma membrane of epithelial cells. Na(+)-K(+)-ATPase presents two types of asymmetries: the arrangement of its subunits, and its expression in one pole of the epithelial cell ("polarity"). In most epithelia, polarity consists of the expression of Na(+)-K(+)-ATPase towards the intercellular space and arises in part from the interaction of the extracellular segment of the ß-subunit with another ß-subunit present in a Na(+)-K(+)-ATPase molecule expressed by a neighboring cell. In addition to enabling the Na(+)-K(+)-ATPase to transport ions and water vectorially, this position exposes its receptors to ouabain and analogous cardiotonic steroids, which are present in the internal milieu because these were secreted by endocrine cells.

Control of tight junctional sealing: roles of epidermal growth factor and prostaglandin E2.

Epithelia can adjust the permeability of the paracellular permeation route by regulating the degree of sealing of the tight junction. This is reflected by a transepithelial electrical resistance (TER) ranging from a few tenths to several thousand ohms times square centimeters, depending on the difference in composition between the fluid in the lumen and the interstitial fluid. Although teleologically sound, such correlation requires a physiological explanation. We have previously shown that urine extracts from different animal species increase the TER of Madin-Darby canine kidney (MDCK) monolayers and that these effects are mediated by epidermal growth factor (EGF) contained in the flowing intratubular fluid that eventually reaches the urine. This increase in TER is accompanied by an enhanced expression of claudin-4 (cln-4) and a decrement of cln-2. These changes are transient, peaking at approximately 16 h and returning to control values in approximately 24 h. In the present work we investigated how EGF provokes this transient response, and we found that the activation of extracellular-regulated kinases 1/2 (ERK1/2) by EGF is essential to increase TER and cln-4 content, but it does not appear to participate in cln-2 downregulation. On the other hand, prostaglandin synthesis, stimulated by EGF, functions as a negative feedback, turning off the signal initiated by EGF. Thus, PGE(2) blocks ERK1/2 by a mechanism that involves the G alpha(s) protein, adenylyl cyclase as well as protein kinase A in MDCK cells. In summary, the permeability of a given segment of the nephron depends on the expression of different claudin types, which may be modulated by EGF and prostaglandins.

Na+,K+-ATPase and hormone ouabain:new roles for an old enzyme and an old inhibitor.

Na+,K+-ATPase and its specific inhibitor ouabain entered the 21st century with an entirely new set of properties, that are the focuses of the present review. (i) The adhesive property of the beta-subunit explains why is Na+,K+-ATPase expressed polarizedly on one side of epithelial cells, a crucial property to explain the exchange of substances between higher organisms and the environment; (ii) Ouabain was recently recognized to be a hormone. (iii) Na+,K+-ATPase is known to act as a receptor for hormone ouabain, (iv) binding of ouabain to the Na+,K+-ATPase modifies adhesion: at high concentrations the outcome is total detachment. (v) Ouabain-resistant cells and ouabain-sensitive ones establish a special type of cell-cell interaction, so that sensitive cells withstand the presence of otherwise lethal levels of ouabain. (vi) Hormone ouabain provokes relocalization of specific molecules from the submembrane scaffold to the nucleus, where these bind to promoters of genes involved in proliferation, differentiation, migration, etc. (vii) Finally, ouabain causes a retrieval of Na+,K+-ATPase from the plasma membrane. We speculate that this would reduce the driving force that operates co- and counter-transporters, which are responsible for the exchange of substances across epithelia.

Ouabain binding to Na+,K+-ATPase relaxes cell attachment and sends a specific signal (NACos) to the nucleus.

Abstract. In previous work we described a "P-->A mechanism" that transduces occupancy of the pump ( P) by ouabain into changes in phosphorylation, stimulation of mitogen-activated protein kinase (MAPK), and endocytosis of cell-cell- and cell-substrate-attaching molecules ( A), thereby causing a release of the cell from the monolayer. In the present work we try to understand the mechanism of this effect; whether, in order to trigger the P-->A mechanism, ouabain should block the pumping activity of Na(+),K(+)-ATPase as pump, or whether it would suffice that the drug occupies this enzyme as a receptor. We assay a series of drugs known to act on the pump, such as ouabain, digoxin, digitoxin, palytoxin, oligomycin, strophanthidin, neothyoside-A, proscillaridin-A, etc. We gauge their ability to block the pump by measuring the K(+) content in the cells, and their ability to detach the cells from the monolayer by determining the amount of protein remaining in the culturing well. None of the drugs tested was able to cause detachment without stopping the pump. Ouabain also enhances phosphorylation, yet pump inhibition and signal transduction do not seem to be intimately associated in a causal chain, but to occur simultaneously. To investigate the response of the site of cell attachment, we analyze the position of beta-catenin by fluorescence confocal microscopy, and find that this adherent junction-associated molecule is sent to the nucleus, where it is known to act as a transcriptional cofactor.