Pharmacogenetics May Prevent Psychotropic Adverse Events in Autism Spectrum Disorder: An Observational Pilot Study.

INTRODUCTION: Up to 73% of individuals with autism spectrum disorder (ASD) and intellectual disability (ID) currently have prescriptions for psychotropic drugs. This is explained by a higher prevalence of medical and psychiatric chronic comorbidities, which favors polypharmacy, increasing the probability of the appearance of adverse events (AEs). These could be a preventable cause of harm to patients with ASD and an unnecessary waste of healthcare resources. OBJECTIVE: To study the impact of pharmacogenetic markers on the prevention of AE appearance in a population with ASD and ID. METHODS: This is a cross-sectional, observational study (n = 118, 72 participants completed all information) in the ASD population. Sociodemographic and pharmacological data were gathered. The Udvalg for Kliniske Undersøgelser Scale (UKU Scale) was used to identify AEs related to the use of psychotropic medication. Polymorphisms of DOP2, ABCB1, and COMT were genotyped and correlated with the AE to find candidate genes. Furthermore, a review of all medications assessed in a clinical trial for adults with autism was performed to enrich the search for potential pharmacogenetic markers, keeping in mind the usual medications. RESULTS: The majority of the study population were men (75%) with multiple comorbidities and polypharmacy, the most frequently prescribed drugs were antipsychotics (69%); 21% of the participants had four or more AEs related to psychotropic drugs. The most common were "Neurological" and" Psychiatric" (both 41%). Statistical analysis results suggested a significant correlation between the neurological symptoms and the DOP2 genotype, given that they are not equally distributed among its allelic variants. The final review considered 19 manuscripts of medications for adults with ASD, and the confirmed genetic markers for those medications were consulted in databases. CONCLUSION: A possible correlation between neurologic AEs and polymorphisms of DOP2 was observed; therefore, studying this gene could contribute to the safety of this population's prescriptions. The following studies are underway to maximize statistical power and have a better representation of the population.

Assessment of the efficacy and tolerance of an innovative regenerative serum on cutaneous regeneration, following fractional laser procedure using Erbium:YAG.

INTRODUCTION: Cutaneous regeneration, fractional laser, medical device, cellular proliferation cutaneous changes linked to photoaging are currently treated with physical treatments, such as fractional laser, which may induce epidermal alteration. OBJECTIVE: To determine the efficacy and safety of a regenerative serum (Matricium® , Laboratoire Bioderma, France) after laser procedure. METHODS: Prospective, double-blind, controlled, and randomized study in subjects with photoaged skin. The regenerative serum of treatment was used after a fractional laser session twice daily for 2 months on 1 side of the face and the placebo on the other side. The main variable to determine efficacy was the improvement of clinical signs and histological and immunological results. RESULTS: A superior quality of epidermal regeneration on the treated side compared to the placebo side was observed. Likewise, a superior and faster clinical improvement on static wrinkles was observed on the hemiface on which the regenerative serum was used. After 60 days, the investigator and the subjects observed a moderate to significant improvement of the skin on the treated side and a mild to moderate improvement on the placebo side. Histological examinations showed a superior thickness of epidermis and higher cellular proliferation rate (Ki67 markers) as well as a superior thickness of dermis with higher increase in elastin density with the regenerative serum compared to placebo. CONCLUSION: The use of the regenerative serum after fractional laser on the face accelerated and improved the cutaneous regeneration on both the clinical and histological level and maximized the benefits of the laser procedure.

Osteotropic polypeptide nanoparticles with dual hydroxyapatite binding properties and controlled cisplatin delivery.

PURPOSE: Nanoparticles with prolonged residence time in bone constitute a valuable strategy for bone disease treatments. The aim of this work was to synthesise a simple nanoparticulate system exhibiting both anticancer and hydroxyapatite binding properties for potential bone cancer applications. METHODS: The amphiphilic copolymer poly(γ-benzyl-glutamate)-block-poly(glutamic acid) (PBLG-b-PGlu) was synthetised by ring opening polymerization and nanoparticles were obtained by a simple nanoprecipitation method. Nanoparticles were characterized in terms of cisplatin interaction, association, and release as well as interaction with hydroxyapatite and their cytoxicity was studied in three prostate cancer cell lines. RESULTS: PBLG-b-PGlu nanoparticles of ~50 nm in size were successfully prepared. They could display for the first time dual hydroxyapatite binding and anticancer properties mediated by the PGlu moiety. They could complex cisplatin at a drug loading content of 6.2% (w/w). Cisplatin release was triggered by physiological concentrations of chloride ions according to an almost zero order kinetics during 14 days. Simultaneously, these nanoparticles showed in vitro hydroxyapatite binding. Finally, they were shown to exert a cytotoxic effect in three prostate cancer cell lines that potentially metastasize to bone. CONCLUSIONS: These properties suggest the potential utility of cisplatin-loaded PBLG-b-PGlu nanoparticles as carrier systems for the treatment of bone metastases.