Recurrent pneumonia post atrial fibrillation ablation: do not forget to look for pulmonary vein stenosis.

A man in his 50s presented with persistent chest pain, haemoptysis, cough and dyspnoea 5 months after undergoing catheter ablation for atrial fibrillation (AF). Several chest CT scans suggested pneumonia. Despite adequate treatment for recurrent pneumonia, symptoms persisted. While reviewing the initial chest CT, a partial venous infarction of the left lower lobe associated with severe left inferior pulmonary vein stenosis (PVS) was diagnosed. Stenting of the left inferior pulmonary vein with a vascular bare metal stent was performed, guided by fluoroscopy and transoesophageal echocardiography. Dual antiplatelet therapy (aspirin/clopidogrel) was introduced for 3 months, followed by long-term aspirin monotherapy. The treatment resulted in relief of his symptoms and the resolution of pulmonary opacities on chest CT. Despite low frequency, AF ablation remains the most common cause of acquired PVS. As highlighted in this case, symptoms are not specific and include recurrent pulmonary infection with delayed management.

[Euglycemic ketoacidosis : a complication of SGLT2 inhibitors]. / Acidocétose euglycémique : une complication des inhibiteurs du SGLT2.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a new category of oral antidiabetics recently indicated for the treatment of type 2 diabetes. Their mechanism of action (inhibition of renal reabsorption of glucose) and the fact that they do not induce hypoglycemia (as monotherapy) make their clinical use interesting. Various adverse events have however been reported regarding these drugs with the euglycemic ketoacidosis being the most serious. In this article we aim to review the possible mechanism of this side effect and recommendations for use of SGLT2 inhibitors by means of a case report.

Les inhibiteurs du SGLT2 (sodium-glucose cotransporter 2) sont une nouvelle catégorie d'antidiabétiques oraux recommandés récemment pour le traitement du diabète de type 2. Leur mécanisme d'action (inhibition de la réabsorption du glucose au niveau rénal) et le fait qu'ils n'induisent pas d'hypoglycémie (en monothérapie) rendent leur profil intéressant. Cependant, plusieurs effets indésirables ont été décrits depuis leur apparition, dont le plus grave est une acidocétose euglycémique. Dans cet article, nous revoyons à la lumière d'un cas les mécanismes probables de cet effet secondaire et les recommandations d'utilisation des inhibiteurs du SGLT2.

MEK-ERK signaling in adult newt retinal pigment epithelium cells is strengthened immediately after surgical induction of retinal regeneration.

Adult newt retinal pigment epithelium (RPE) cells are mitotically quiescent in the physiological condition, but upon a traumatic injury of the neural retina (NR) they re-enter the cell-cycle and eventually regenerate the missing NR. Here, to understand the mechanism underlying the cell-cycle re-entry of RPE cells following NR injury, we first investigated changes in MEK-ERK signaling activity in RPE cells upon removal of the NR (retinectomy) from the eye of living animals, and found that ERK-mediated signaling activity is elevated quickly (in 30 min) upon retinectomy. In addition, we found, in in vitro analyses, that immediate early activation of MEK-ERK signaling may occur in RPE cells upon NR injury, intensifying the MEK-ERK signaling itself through up-regulation of the expression of constituent molecules in the pathway, and that 1-h blockade of such early MEK-ERK signaling interferes with the cell-cycle re-entry, which occurs 5-10 days later. Together, these results provide us with insight that elevation of MEK-ERK signaling activity upon NR injury may be a key process for mitotically quiescent RPE cells to re-enter the cell-cycle, leading to retinal regeneration.

Metamorphosis inhibition: an alternative rearing protocol for the newt, Cynops pyrrhogaster.

The newt is an indispensable model animal, of particular utility for regeneration studies. Recently, a high-throughput transgenic protocol was established for the Japanese common newt, Cynops pyrrhogaster. For studies of regeneration, metamorphosed animals may be favorable; however, for this species, there is no efficient protocol for maintaining juveniles after metamorphosis in the laboratory. In these animals, survival drops drastically after metamorphosis as their foraging behaviour changes to adapt to a terrestrial habitat, making feeding in the laboratory with live or moving foods more difficult. To elevate the efficiency of laboratory rearing of this species, we examined metamorphosis inhibition (Ml) protocols to bypass the period (four months to two years after hatching) in which the animal feeds exclusively on moving foods. We found that approximately 30% of animals survived after 2-year Ml, and that the survivors continuously grew, only with static food while maintaining their larval form and foraging behaviour in 0.02% thiourea (TU) aqueous solution, then metamorphosed when returned to a standard rearing solution even after 2-year-MI. The morphology and foraging behavior (feeding on static foods in water) of these metamorphosed newts resembled that of normally developed adult newts. Furthermore, they were able to fully regenerate amputated limbs, suggesting regenerative capacity is preserved in these animals. Thus, controlling metamorphosis with TU allows newts to be reared with the same static food under aqueous conditions, providing an alternative rearing protocol that offers the advantage of bypassing the critical period and obtaining animals that have grown sufficiently for use in regeneration studies.

MEK-ERK and heparin-susceptible signaling pathways are involved in cell-cycle entry of the wound edge retinal pigment epithelium cells in the adult newt.

The onset mechanism of proliferation in mitotically quiescent retinal pigment epithelium (RPE) cells is still obscure in humans and newts, although it can be a clinical target for manipulating both retinal diseases and regeneration. To address this issue, we investigated factors or signaling pathways involved in the first cell-cycle entry of RPE cells upon retinal injury using a newt retina-less eye-cup culture system in which the cells around the wound edge of the RPE exclusively enter the cell cycle. We found that MEK-ERK signaling is necessary for their cell-cycle entry, and signaling pathways whose activities can be modulated by heparin, such as Wnt-, Shh-, and thrombin-mediated pathways, are capable of regulating the cell-cycle entry. Furthermore, we found that the cells inside the RPE have low proliferation competence even in the presence of serum, suggesting inversely that a loss of cell-to-cell contact would allow the cells to enter the cell cycle.