Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HP's antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low-hyperforin-content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P-glycoprotein, of which many drugs are substrates and which are the main origin of HP-drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP-drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP.

Introduction:Spontaneous reporting of adverse drug reactions (ADRs) is the basis of pharmacovigilance. In fact, ADRs are associated with a high degree of morbidity and mortality. However, underreporting by all healthcare professionals remains the major problem in Italy and in the rest of the world. The dissemination of pharmacovigilance knowledge among Italian healthcare professionals, and the new pharmacovigilance regulations may promote the early detection and reporting of ADRs. This review examines the legislative framework concerning the pharmacovigilance in Italy.Materials and Methods:The information was collected from scientific articles and the websites of the Italian Ministry of Health and the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA).Results:The pharmacovigilance system, both in Italy and Europe, has undergone profound changes. European legislation on pharmacovigilance has been changed in 2010 according to the EU Regulation 1235/2010 and Directive 2010/84/EU. Basically, the changes tend to increase the efficiency, speed and transparency of pharmacovigilance activities. The new Regulation (1235/2010) and the Directive (2010/84/EU) aim to strengthen the system of pharmacovigilance, establish more precisely who is obliged to do what, and allow faster and easier circulation and retrieval of information about ADRs.Conclusion:A greater knowledge on what is the Italian pharmacovigilance legislation will be useful to improve the status of ADRs reporting and spread the culture of spontaneous reporting.

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With the further tightening of emission regulations and the introduction of real driving emission tests (RDE), the simulative prediction of emissions is becoming increasingly important for the development of future low-emission internal combustion engines. In this context, gas-exchange simulation can be used as a powerful tool for the evaluation of new design concepts. However, the simplified description of the combustion chamber can make the prediction of complex in-cylinder phenomena like emission formation quite challenging. The present work focuses on the prediction of gaseous pollutants from a spark-ignition (SI) direct injection (DI) engine with 1D–0D gas-exchange simulations. The accuracy of the simulative prediction regarding gaseous pollutant emissions is assessed based on the comparison with measurement data obtained with a research single cylinder engine (SCE). Multiple variations of engine operating parameters – for example, load, speed, air-to-fuel ratio, valve timing – are taken into account to verify the predictivity of the simulation toward changing engine operating conditions. Regarding the unburned hydrocarbon (HC) emissions, phenomenological models are used to estimate the contribution of the piston top-land crevice as well as flame wall-quenching and oil-film fuel adsorption-desorption mechanisms. Regarding CO and NO emissions, multiple approaches to describe the burned zone kinetics in combination with a two-zone 0D combustion chamber model are evaluated. In particular, calculations with reduced reaction kinetics are compared with simplified kinetic descriptions. At engine warm operation, the HC models show an accuracy mainly within 20%. The predictions for the NO emissions follow the trend of the measurements with changing engine operating parameters and all modeled results are mainly within ±20%. Regarding CO emissions, the simplified kinetic models are not capable to predict CO at stoichiometric conditions with errors below 30%. With the usage of a reduced kinetic mechanism, a better prediction capability of CO at stoichiometric air-to-fuel ratio could be achieved.

The development and validation of detailed simulation models of incylinder combustion, emission formation mechanisms and reaction kinetics in the exhaust system are of crucial importance for the design of future low-emission powertrain concepts. To investigate emission formation mechanisms on one side and to create a solid basis for the validation of simulation methodologies (e.g. 3D-CFD, multidimensional in-cylinder models, etc.) on the other side, specific detailed measurements in the exhaust system are required. In particular, the hydrocarbon (HC) emissions are difficult to be investigated in simulation and experimentally, due to their complex composition and their post-oxidation in the exhaust system.In this work, different emission measurement devices were used to track the emission level and composition at different distances from the cylinder along the exhaust manifold, from the exhaust valve onwards. A fast-FID (FFID) was used to measure the cycle-resolved total-HC (THC) emissions and an ion molecule reaction massspectrometer (IMR-MS) to determine the average concentration of some selected HC components. Conventional exhaust analyzers were used additionally to measure the average levels of the important exhaust gas components (THC, NOx, CO, CO2, O2).The measurements were conducted on a 0.4 l single-cylinder sparkignited (SI) research engine. The effects and cross-effects on emissions of several relevant operating parameters were evaluated. Different result patterns are observed in the different measuring positions. In this work, selected results on the effect of air-to-fuel ratio and spark timing are presented. For the air-fuel-ratio variation, the FFID results show that the THC quenching increases with lean operating condition and the IMR-MS that this increase corresponds to an increase in fuel-HC and a reduction in non-fuel-HC. In the spark timing variation, the trends of THC in the exhaust port and in the exhaust runner suggest the presence of HC oxidation in the exhaust port, due to higher exhaust temperature with retarded combustion. Additionally, the IMR-MS confirm the presence of late and incomplete oxidation with the increase of non-fuel species.

Introduction:Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010.Materials and Methods:We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs.Results:A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar®), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups “41-65” (39.07%) and “over 65” (27.9%) were the most affected.Conclusions:Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed.

Food legumes are at the crossroads of many societal challenges that involve agriculture, such as climate change and food sustainability and security. In this context, pulses have a crucial role in the development of plant-based diets, as they represent a very good source of nutritional components and improve soil fertility, such as by nitrogen fixation through symbiosis with rhizobia. The main contribution to promotion of food legumes in agroecosystems will come from plant breeding, which is guaranteed by the availability of well-characterized genetic resources. Here, we analyze seeds of 25 American and European common bean purified accessions (i.e., lines of single seed descent) for different morphological and compositional quality traits. Significant differences among the accessions and superior genotypes for important nutritional traits are identified, with some lines showing extreme values for more than one trait. Heritability estimates indicate the importance of considering the effects of environmental growth conditions on seed compositional traits. They suggest the need for more phenotypic characterization in different environments over different years to better characterize combined effects of environment and genotype on nutritional trait variations. Finally, adaptation following the introduction and spread of common bean in Europe seems to have affected its nutritional profile. This finding further suggests the relevance of evolutionary studies to guide breeders in the choice of plant genetic resources.