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.
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.
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