[Which alternative to benzodiazepines, Z-pills and other hypnotics for aged people ? Melatonin, valerian, or clomethiazole]. / Quelle alternative aux benzodiazépines, Z-pills et autres hypnotiques pour les personnes âgées ?: Mélatonine, valériane ou clométhiazole.

Sleep disorders are a recurrent complaint in geriatrics. Of multifactorial origin, they have a significant impact on health and quality of life. However, the answer is (too) often the prescription of benzodiazepines or related-drugs (Z-pills), sedative antidepressant, or another psychotropic medication. More recently, melatonin, valerian and, in Switzerland, clomethiazol are widely considered as effective and more suitable alternatives for aged people. We present a systematic review of the literature on the efficacy and tolerance of these molecules, of which the main objective is to demonstrate that non-pharmacological approach must remain the first-line therapy of insomnia in geriatrics.

Les troubles du sommeil sont une plainte récurrente en gériatrie. D'origine multifactorielle, ils ont un retentissement significatif sur la santé et la qualité de vie. Cependant la réponse est (trop) souvent la prescription de benzodiazépines ou apparentés (Z-pills), d'un antidépresseur sédatif ou d'un autre psychotrope. Plus récemment, la mélatonine, la valériane et, en Suisse, le clométhiazole sont largement utilisés car considérés comme des alternatives efficaces et plus adaptées aux personnes âgées. Nous présentons une revue systématique de la littérature sur l'efficacité et la tolérance de ces molécules dont l'objectif principal est de montrer que les mesures non pharmacologiques doivent rester le traitement de première intention des insomnies en gériatrie.

Withanolide D Enhances Radiosensitivity of Human Cancer Cells by Inhibiting DNA Damage Non-homologous End Joining Repair Pathway.

Along with surgery and chemotherapy, radiation therapy (RT) is an important modality in cancer treatment, and the development of radiosensitizers is a current key challenge in radiobiology to maximize RT efficiency. In this study, the radiosensitizing effect of a natural compound from the withanolide family, withanolide D (WD), was assessed. Clonogenic assays showed that a 1 h WD pretreatment (0.7 µM) before irradiation decreased the surviving fraction of several cancer cell lines. To determine the mechanisms by which WD achieved its radiosensitizing effect, we then assessed whether WD could promote radiation-induced DNA damages and inhibit double-strand breaks (DSBs) repair in SKOV3 cells. Comet and γH2AX/53BP1 foci formation assays confirmed that DSBs were higher between 1 and 24 h after 2 Gy-irradiation in WD-treated cells compared to vehicle-treated cells, suggesting that WD induced the persistence of radiation-induced DNA damages. Immunoblotting was then performed to investigate protein expression involved in DNA repair pathways. Interestingly, DNA-PKc, ATM, and their phosphorylated forms appeared to be inhibited 24 h post-irradiation in WD-treated samples. XRCC4 expression was also down-regulated while RAD51 expression did not change compared to vehicle-treated cells suggesting that only non-homologous end joining (NHEJ) pathways was inhibited by WD. Mitotic catastrophe (MC) was then investigated in SKOV3, a p53-deficient cell line, to assess the consequence of such inhibition. MC was induced after irradiation and was predominant in WD-treated samples as shown by the few numbers of cells pursuing into anaphase and the increased amount of bipolar metaphasic cells. Together, these data demonstrated that WD could be a promising radiosensitizer candidate for RT by inhibiting NHEJ pathway and promoting MC. Additional studies are required to better understand its efficiency and mechanism of action in more relevant clinical models.