After an initial screening of ingredients and production methods, nanoemulsions for ocular administration of timolol containing the drug as maleate (TM) or as ion-pair with AOT (TM/AOT) were prepared. The physico-chemical characterization of nanoemulsions, regarding mean diameter, pH, zeta potential, osmolarity, viscosity and surface tension, underlined their feasibility to be instilled into the eyes. Single components and emulsions were tested ex vivo on rabbit corneas to evaluate corneal irritation, that was measured according to opacity test. A marked decrease in corneal opacity was observed using the drug formulated in nanoemulsions rather than in aqueous solutions. Drug permeation and accumulation studies were performed on excised rabbit corneas. An increase in drug permeation through and accumulation into the corneas were observed using TM-AOT compared to TM due to an increase of lipophilicity of the drug as ion-pair. The introduction of chitosan (a positive charged mucoadhesive polymer) into emulsions allowed to increase TM permeation probably due to the interaction of chitosan with corneal epithelial cells.

Cannabis has long been regarded as a recreational substance in the Western world. The recent marketing authorization of some medicinal products of industrial origin and the introduction onto the market of inflorescences for medical use mean that medical doctors can now prescribe Cannabis-based medicines in those countries which allow it. Nevertheless, there is still considerable controversy on this topic in the scientific community. In particular, this controversy concerns: the plant species to be used; the pathologies that can be treated and consequently the efficacy and safety of use; the routes of administration; the methods of preparation; the type and dosage of cannabinoids to be used; and, the active molecules of interest. As such, although medical Cannabis has been historically used, the results of currently completed and internationally published studies are inconclusive and often discordant. In light of these considerations, the aim of this work is to analyse the current legislation in countries that allow the use of medical Cannabis, in relation to the impact that this legislation has had on clinical trials. First of all, a literature search has been performed (PubMed and SciFinder) on clinical trials which involved the administration of Cannabis for medical use over the last 3 years. Of the numerous studies extrapolated from the literature, only about 43 reported data on clinical trials on medical Cannabis, with these mainly being performed in Australia, Brazil, Canada, Denmark, Germany, Israel, Netherlands, Switzerland, the United Kingdom and the United States of America. Once the reference countries were identified, an evaluation of the legislation in relation to Cannabis for medical use in each was carried out via the consultation of the pertinent scientific literature, but also of official government documentation and that of local regulatory authorities. This analysis provided us with an overview of the different legislation in these countries and, consequently, allowed us to analyse, with greater awareness, the results of the clinical trials published in the last 3 years in order to obtain general interest indications in the prosecution of scientific research in this area.

Headache disorders are considered the second leading cause of years lived with disability worldwide, and 90% of people have a headache episode at least once a year, thus representing a relevant public health priority. As the pharmacist is often the first and only point of reference for people complaining of headache, we carried out a survey in a nationwide sample of Italian pharmacies, in order to describe the distribution of migraine or non-migraine type headaches and medicines overuse among people entering pharmacies seeking for self-medication; and to evaluate the association, in particular of migraine, with socio-demographic and clinical characteristics, and with the pathway of care followed by the patients. A 14-item questionnaire, including socio-demographic and clinical factors, was administered by trained pharmacists to subjects who entered a pharmacy requesting self-medication for a headache attack. The ID Migraine^™ Screener was used to classify headache sufferers in four classes. From June 2016 to January 2017, 4424 people have been interviewed. The prevalence of definite migraines was 40%, significantly higher among women and less educated people. About half of all headache sufferers and a third of migraineurs do not consider their condition as a disease and are not cared by any doctor. Among people seeking self-medication in pharmacies for acute headache attacks, the rate of definite or probable migraine is high, and a large percentage of them is not correctly diagnosed and treated. The pharmacy can be a valuable observatory for the study of headaches, and the first important step to improve the quality of care delivered to these patients.

Pyridoxamine, a structural analog of vitamin B6 that exerts antiglycative effects, has been proposed as supplementary approach in patients with initial diabetic nephropathy. However, the molecular mechanism(s) underlying its protective role has been so far slightly examined. C57Bl/6J mice were fed with a standard diet (SD) or a diet enriched in fat and fructose (HD) for 12 weeks. After 3 weeks, two subgroups of SD and HD mice started pyridoxamine supplementation (150 mg/kg/day) in the drinking water. HD fed mice showed increased body weight and impaired glucose tolerance, whereas pyridoxamine administration significantly improved insulin sensitivity, but not body weight, and reduced diet-induced increase in serum creatinine and urine albumin. Kidney morphology of HD fed mice showed strong vacuolar degeneration and loss of tubule brush border, associated with a drastic increase in both advanced glycation end products (AGEs) and AGEs receptor (RAGE). These effects were significantly counteracted by pyridoxamine, with consequent reduction of the diet-induced overactivation of NF-kB and Rho/ROCK pathways. Overall, the present study demonstrates for the first time that the administration of the antiglycative compound pyridoxamine can reduce the early stages of diet-dependent kidney injury and dysfunction by interfering at many levels with the profibrotic signaling and inflammatory cascades.