Alnus glutinosa (L.) Gaertn. and Alnus cordata (Loisel) Duby as new sources of safe cosmetic and pharmacological anti-melanogenic agents

The genus Alnus (Betulaceae) comprises many species with a long history in traditional medicines. The crude extracts and isolated compounds from Alnus species exhibit a wide spectrum of in vitro and in vivo pharmacological activities (1). Phytochemical investigations revealed the presence of diarylheptanoids, a class of natural products typically found in Alnus genus with two aryl groups joined by a heptane chain in the main skeleton that have drawn attention due to their multiple biological properties and their therapeutic potential (2). A previous study reported that oregonin and other structurally analogous diarylheptanoids isolated from the bark of A. hirsuta showed inhibitory effects on melanogenesis in B16 melanoma cells.(3). Nowadays the discovery of new whitening agents from natural sources is increasing, due to the weak effectiveness and unwanted side effects of currently available compounds. In this context, the aim of this study was to evaluate the skin whitening capabilities of crude extracts (80% aqueous MeOH) obtained from the fresh bark of Alnus glutinosa (L.) Gaertn. and Alnus cordata (Loisel) Duby, an endemic species in the Mediterranean areas (4). As tyrosinase is the rate-limiting enzyme in melanin biosynthesis, the inhibitory effects of A. glutinosa and A. cordata extracts (AGE and ACE, respectively) on mushroom tyrosinase activity were preliminary evaluated. In addition, the anti-melanogenic ability of AGE and ACE was further investigated on the pigmentation of early stage zebrafish at 72 hours post fertilization (hpf) to find new skin whitening agents without cytotoxic concerns. Results of the enzymatic assay showed that ACE was capable to inhibit dose dependently L-DOPA oxidation catalyzed by tyrosinase (IC50 = 77.44 \ub1 0.54 \u3bcg/mL) as compared to the reference inhibitor kojic acid (2.24 \ub1 0.18 \u3bcg/mL). Unlike, AGE exhibited a lower anti-tyrosinase activity (100 \u3bcg/mL reached 28% of inhibition while higher doses showed pro-oxidative effects). Moreover, the zebrafish in vivo assay revealed that ACE (50 \u3bcg/mL) has equivalent inhibitory effects on the pigmentation (76.57%) to that of phenylthiourea (PTU, 30 \u3bcg/mL), used as the reference inhibitor (77.80%), as compared to control, while they did not affect the embryos development and survival. Conversely, the depigmenting effects of AGE were about 10 fold less than ACE (45.28% at 500 \u3bcg/mL). A mild anti-melanogenic activity was also evidenced for the diarylheptanoid oregonin (10% of inhibition at 20 \u3bcg/mL). A preliminary phytochemical screening evidenced that ACE and AGE have a high phenolic content (399.27 \ub1 14.30 and 534.17 \ub1 20.60 mg GAE/g of extract, respectively). However, despite AGE showed the highest phenolic content, the quali-quantitative RP-HPLC-DAD analysis highlighted as it is predominantly composed by oregonin (418.45 \u3bcg/mg of AGE vs 1.23 \u3bcg/mg of ACE) that exhibited a mild anti-melanogenic activity both in vitro and in vivo assays. Further phytochemical investigations are still in progress to identify the bioactive compounds of ACE as to be considered a potential candidate for the treatment of skin disorders due to its bleaching properties and favorable safety profiles

Presupposti epistemologici della valutazione/misurazione

Analisi della nozione di valutazione, in relazione a quella di commisurazione e ai sistemi di (neo)valutazione della ricerca scientifica

Best practices in European restructuring contractualised distress resolution in the shadow of the law. Italian National Findings Italian National Report

The general trend away from traditional, formal insolvency proceedings opens up a vast area to private ordering, with all the associated opportunities and risks. The transition can be less costly if the resulting uncertainty is reduced to a minimum. This presents national legislators with a delicate challenge. They should not be overly prescriptive and should effectively delegate decision-making to stakeholders and expert professionals, who are likely to be better informed and better incentivised. At the same time, the law must provide for information to fow where needed and for the creation of optimal incentives. Against this background, guidance on best practices can be of great value. It may assist policymaking in one jurisdiction by drawing attention to successes and failures in others, and it may allow professionals, advisors, debtors, creditors and courts to fnd common ground in the formulation of high-quality distress resolution plans and in distinguishing viable and non-viable distressed debtors. Based on extensive empirical research in four European Union states, this book takes up the challenge of unearthing and crystallising some of the most critical best practices in the various stages of a distress resolution process. Drawing on these best practices, it provides lawmakers with several \u2018Policy Recommendations\u2019, and other key stakeholders with a set of \u2018Guidelines\u2019. Special attention is given to the particular needs of micro, small and medium enterprises

Phenotyping normal kidney function in elderly patients with type 2 diabetes: a cross-sectional multicentre study

AIMS: Type 2 diabetes (T2D) accelerates the decline in glomerular function; however, some individuals do not develop chronic kidney disease despite advanced age and long-lasting T2D. We aimed to phenotype patients with T2D aged 80 years or older who presented with a fully preserved kidney function. METHODS: From an Italian population of 281,217 T2D outpatients, we collected data on demographics, anthropometrics, diabetes duration, HbA1c, fasting plasma glucose, lipids, liver enzymes, estimated glomerular filtration rate (eGFR), albumin excretion rate (AER), chronic complications, and medication use. We primarily compared patients with a fully preserved kidney function (eGFR\u2009>\u200990 ml/min/1.73 m2 and AER\u2009<\u200930 mg/24 h, or G1A1) with those with mild kidney impairment (eGFR 60-90 ml/min/1.73 m2 and AER\u2009<\u200930 mg/24 h, or G2A1). RESULTS: N\u2009=\u2009113,860 had available data for eGFR and AER, 21,648 of whom were aged\u2009 65\u200980. G1A1 (n\u2009=\u2009278) and G2A1 (n\u2009=\u20096647) patients represented 1.3 and 30.7% of aged T2D patients, respectively, with an average diabetes duration of 16 years. Differences between the G1A1 and G2A1 groups were entered in a multiple logistic regression analysis with and without imputation of missing data. After adjustment and in both imputed and non-imputed datasets, younger age, lower BMI and lower triglycerides were associated with fully preserved versus mildly impaired kidney function. The comparison between G1A1 and G1A2/3 yielded different results. CONCLUSIONS: In a rare population of patients with a fully preserved kidney function despite old age and long-lasting diabetes, lower BMI and triglycerides suggest that protection from lipotoxicity may preserve kidney function over time

Frequency of Left Ventricular Hypertrophy in Non-Valvular Atrial Fibrillation

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention