Comparison of the Effects of Adenosine, Inosine, and Their Combination as an Adjunct to Reperfusion in the Treatment of Acute Myocardial Infarction

Adenosine and inosine are both key intracellular energy substrates for nucleotide synthesis by salvage pathways, especially during ischemic stress conditions. Additionally they both possess cell protective and cell repair properties. The objective of this study is to detect potential advantages of the combination of adenosine and inosine versus each drug alone, in terms of ventricular function, infarct size reduction and angiogenesis. Myocardial ischemia was created in rodents and treated with adenosine, inosine or their combination. Results of experiments showed that the combination of both drugs significantly reduced infarct size and improved myocardial angiogenesis and ventricular function. The two compounds, while chemically similar, use different intracellular pathways, allowing for complementary biological activities without overlapping. The drug combination at specific 1 : 5 adenosine : inosine dose ratio demonstrated positive cardiologic effects, deserving further evaluation as an adjunct to reperfusion techniques during and after acute coronary syndrome. The association of adenosine and inosine may contribute to reduce myocardial infarction morbidity and mortality rates

Muco-ciliary differentiation of nasal epithelial cells is decreased after wound healing in vitro.: Muco-ciliary differentiation & wound healing

International audienceBACKGROUND: Epithelial damage and modifications of cell differentiation are frequent in airway diseases with chronic inflammation, in which transforming growth factor-beta1 (TGF-beta1) plays an important role. The aim of this study was to evaluate the differentiation of human nasal epithelial cells (HNEC) after wound healing and the potential effects of TGF-beta1. METHODS: Basal, mucus, and ciliated cells were characterized by cytokeratin-14, MUC5AC, and betaIV tubulin immunodetection, respectively. Their expression was evaluated in situ in nasal polyps and in an in vitro model of wound healing in primary cultures of HNEC after wound closure, under basal conditions and after TGF-beta1 supplementation. Using RT-PCR, the effects of TGF-beta1 on MUC5AC and DNAI1 genes, specifically transcribed in mucus and ciliated cells, were evaluated. RESULTS: In situ, high TGF-beta1 expression was associated with low MUC5AC and betaIV tubulin expression. In vitro, under basal conditions, MUC5AC expression remained stable, cytokeratin-14 expression was strong and decreased with time, while betaIV tubulin expression increased. Transforming growth factor-beta1 supplementation downregulated MUC5AC and betaIV tubulin expression as well as MUC5AC and DNAI1 transcripts. CONCLUSION: After a wound, differentiation into mucus and ciliated cells was possible and partially inhibited in vitro by TGF-beta1, a cytokine that may be involved in epithelial remodeling observed in chronic airway diseases

Recommandations pour l'évaluation et la prise en charge de la maladie de Lapeyronie : rapport du comité d'andrologie et de médecine sexuelle de l'AFU

International audienceIntroductionPeyronie's disease is a common cause for consultation in urology. Many controversies surround its treatment. No French Guidelines have been published so far. The Committee of Andrology and Sexual Medicine of the French Association of Urology therefore offers a series of evidence-based recommendations.Materials and methodsThese recommendations are made according to the ADAPTE method, based on European (EAU, ESSM), American (AUA, ISSM) and Canadian (CAU) recommendations, integrating French specificities due to the availability of treatments, and an update of the recent bibliography.ResultsThe assessment of the disease is clinical. Patients with functional impairment or significant psychological repercussions may be offered treatment. The benefits and drawbacks of each treatment should be explained to the patient. Regarding non-surgical treatments, no available treatment has market authorization in France. Vitamin E is not recommended. Analgesic (oral or low-intensity shock waves) or proerectile treatments may be offered as needed, as well as traction therapy. Due to the unavailability of collagenase injections, verapamil injections may be offered. Surgical treatments are to be considered in the stabilized phase of the disease, and consist of performing a plication, an incision-graft or the placement of a penile implant according to the patient's wishes, the curvature and the penis size, as well as erectile function. Combination treatments can be offered.ConclusionThe management of Peyronie's disease is complex, and the levels of evidence for treatments are generally low. The success of treatment will depend on the quality of the initial assessment, the patient's information and understanding of the expected effects, and the practitioner's experience.IntroductionLa maladie de Lapeyronie est un motif fréquent de consultation en urologie, dont le traitement reste sujet à de nombreuses controverses. Elle n’a fait l’objet d’aucune recommandation française jusqu’à présent. Le Comité d’Andrologie et de Médecine Sexuelle de l’Association Française d’Urologie propose donc une série de recommandations basées sur les preuves.Matériels et méthodesCes recommandations sont réalisées selon la méthode ADAPTE, en se basant sur les recommandations européennes (EAU, ESSM), américaines (AUA, ISSM) et canadiennes (CAU), en intégrant les spécificités françaises en raison de la disponibilité des traitements, et une mise à jour de la bibliographie récente.RésultatsL’évaluation de la maladie est clinique. Les patients présentant une gêne fonctionnelle ou un retentissement psychologique important peuvent se voir proposer un traitement. Les bénéfices et inconvénients de chaque traitement devront être explicités au patient. Concernant les traitements non chirurgicaux, aucun traitement disponible n’a l’autorisation de mise sur le marché en France. La vitamine E n’est pas recommandée. Des traitements à visée antalgiques (oraux ou ondes de choc de faible intensité) ou pro-érectiles peuvent être proposée selon le besoin, ainsi qu’une thérapie par traction. En raison de l’indisponibilité des injections de collagénase, les injections de vérapamil peuvent être proposées. Les traitements chirurgicaux sont à considérer en phase stabilisée de la maladie, et consistent en la réalisation d’une plicature, d’une incision-greffe ou de la pose d’un implant pénien en fonction du souhait du patient, de la courbure et de la taille de verge, ainsi que de la fonction érectile. Des traitements combinés peuvent être proposés.ConclusionLa prise en charge de la maladie de Lapeyronie est complexe, et les niveaux de preuve des traitements sont faibles dans l’ensemble. Le succès du traitement dépendra de la qualité de l’évaluation initiale, de l’information du patient et de sa compréhension des effets attendus, et de l’expérience du praticien