The Role of PK/PD Analysis in the Development and Evaluation of Antimicrobials

Pharmacokinetic/pharmacodynamic (PK/PD) analysis has proved to be very useful to establish rational dosage regimens of antimicrobial agents in human and veterinary medicine. Actually, PK/PD studies are included in the European Medicines Agency (EMA) guidelines for the evaluation of medicinal products. The PK/PD approach implies the use of in vitro, ex vivo, and in vivo models, as well as mathematical models to describe the relationship between the kinetics and the dynamic to determine the optimal dosing regimens of antimicrobials, but also to establish susceptibility breakpoints, and prevention of resistance. The final goal is to optimize therapy in order to maximize efficacy and minimize side effects and emergence of resistance. In this review, we revise the PK/PD principles and the models to investigate the relationship between the PK and the PD of antibiotics. Additionally, we highlight the outstanding role of the PK/PD analysis at different levels, from the development and evaluation of new antibiotics to the optimization of the dosage regimens of currently available drugs, both for human and animal use.This research was funded by the Department of Education of the Basque Government (PIBA 2019-57) and by the University of the Basque Country UPV/EHU (GIU 17/32)

Effects of Biodanza on Stress, Depression, and Sleep Quality in University Students

Background: The existing literature shows dance to be an innovative and successful form of stress management. Previous research indicates that Biodanza is able to increase well-being and personal resources and prevent stress. However, Biodanza has not yet been empirically tested as a possible therapy for application outside the clinical context in young adults with perceived stress. Objectives: This study aimed to determine the effectiveness of Biodanza in reducing symptoms of perceived stress and depression and in promoting sleep quality in young adults, comparing the changes with those observed in a control group. Design: Randomized controlled trial. Settings/Location: This study was carried out at the Faculty of Health Sciences of the University of Almería. Subjects: One hundred and twenty-one university students with perceived stress were randomly placed into either a Biodanza group or a wait-list control group. Intervention: Study participants attended Biodanza sessions for 90 min a week, over a period of 4 weeks. Outcome measures: Depression, perceived stress, and sleep quality were assessed both before and after intervention. Results: Ninety-five participants completed the program and were included in the statistical analysis. Significant differences in perceived stress [t (93) = 2.136; p = 0.015] and depression [t (93) = 2.738; p = 0.000] were observed after the Biodanza period. Pre/post analysis found that Biodanza also had a significant effect on depression (Cohen d = 1.88; p < 0.05) and perceived stress (Cohen d = 0.79; p < 0.05). Conclusion: The Biodanza program is an effective stress management strategy for students. The results of this study showed Biodanza to have a positive effect on perceived stress and depression in young adults. This demonstrates how artistic, collaborative, and psychophysical interventions are an effective means of preventing and managing these problems in university students

Proteins reversibly oxidized in cysteines in endothellial cells in response to acute hypoxia

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The relevance of music therapy in paediatric and adolescent cancer patients: a scoping review

Background: Music therapy is an emerging and useful methodology to improve the quality of life of children and adolescents with cancer. Objectives: The objective of this scoping review was to examine the available literature and offer an analysis of the relevance of music therapy in paediatric oncology. We considered the effects of music therapy on children and adolescents with cancer as well as the perception of this population, their families, music therapists, and health professionals regarding the music therapy sessions conducted. Finally, we analysed the characteristics of the distinct types of music therapy interventions reported in the literature. Methods: In this review, we applied the methodology proposed by Arksey and O’Malley. After performing a comprehensive academic literature database search, 522 articles were identified of which, 27 met the inclusion criteria. Results: The results shed light on the use of music therapy as a means to facilitate self-esteem, to improve the physical, emotional, and cognitive aspects related to disease and, to a lesser extent, alleviate their physiological symptoms. Both children and adolescents with cancer were represented in the academic literature. The most prevalent findings described in these studies were the benefits of music therapy in terms of improved psychological well-being and social relationships in this population. Conclusions: Music therapy interventions are generally well received, not only by children and adolescents with cancer, but also by their families, music therapists, and health professionals. Nevertheless, several gaps were identified in some of the studies we considered, including a lack of specificity regarding the results obtained or music therapy intervention methods used

Testing edible mushrooms to inhibit the pancreatic lipase activity by an in vitro digestion model

This is the peer reviewed version of the following article: Palanisamy, M. Testing edible mushrooms to inhibit the pancreatic lipase activity by an in vitro digestion model (2012) International Journal of Food Science and Technology, 47 (5), pp. 1004-1010., which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2621.2011.02934.x. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archivingOne of the strategies in prevention or treatment of obesity is altering metabolism of lipids by inhibition of dietary fat absorption. The extracts obtained with methanol, water and methanol:water (1:1) from 21 mushroom species were screened as potential sources of pancreatic lipase (PL) inhibitors using a standardised in vitro test. Lepiota procera methanol:water (1:1) extracts showed the highest inhibition activity closely followed by Grifola frondosa, Pleurotus eryngii and Lyophyllum shimeji. Other mushroom strains such as Morchella conica, Marasmius oreades, Lentinula edodes, Amanita ponderosa and Boletus edulis also showed a certain inhibitory activity. However, when the PL inhibitory activity was evaluated using an in vitro digestion model mimicking gut conditions, none of the selected mushroom extracts were able to inhibit PL activity. On the contrary, stimulation of the lipase activity levels was observed and it was not due to endogenous mushroom lipases activitiesThe research was supported by the European Union within the 7th framework programme (7FM-PEOPLE-2009-IIF project 251285), ALIBIRD-CM S2009 ⁄AGR-1469 regional program from the Community of Madrid (Spain) and AGL2010-21537 national R+D program from the Spanish Ministry of Science and Innovatio

Pharmacokinetic/pharmacodynamic analysis as a tool for surveillance of the activity of antimicrobials against Pseudomonas aeruginosa strains isolated in critically ill patients

Introduction: To evaluate the changes in the susceptibility of Pseudomonas aeruginosa overtime (2000–2017) against antimicrobials used in an intensive care unit of a Spanish tertiaryhospital, and to compare them with the antimicrobial activity considering theoretical pharmacoki-netic/pharmacodynamic (PK/PD) criteria. The influence of the method for handling duplicate isolatesto quantify susceptibility rates was also evaluated.Methods: The susceptibility was studied considering the Clinical and Laboratory Standards Institute (CLSI)breakpoints. Monte Carlo simulations were conducted to calculate the cumulative fraction of response(CFR). Linear regression analysis was applied to determine the trends in susceptibility and in the CFR.Results: A significant decrease in the susceptibility to gentamicin and imipenem was observed, and morerecently the highest percentages of susceptible strains were found for amikacin, cephalosporins andpiperacillin/tazobactam (>80%). The probability of success of an empiric treatment or CFR for most of theevaluated antimicrobials was lower than 70% during the last two-year period. Only meropenem providedhigh probabilities (>90%) to achieve the PK/PD target. Cephalosporins provided moderate probabilities(>80%) although for ceftazidime, the highest dose (2 g/8 h) was required. Moreover, a significant decreasein the CFR trend for ciprofloxacin, imipenem and levofloxacin was observed.Conclusions: Both susceptibility rates and CFR values have to be considered together to optimize theantimicrobial dose regimen for clinical making-decisions. They are complementary tools and, theyshould be used jointly in surveillance programmes. In fact, susceptibility data are not always usefulto detect changes in the CFR. No relevant differences were observed among the methods for handlingrepeated isolates.This work was supported by the UPV/EHU (PPG17/65,GIU17/032). A Valero thanks Universia Foundation for her grant

Augmented Renal Clearance in Critically Ill Patients: A Systematic Review

Background Traditionally, renal function in critically ill patients has been assessed to identify renal dysfunction, and dose adjustment is generally accepted in such a context. Nevertheless, augmented renal clearance (ARC) is a less well-studied phenomenon that could lead to faster elimination of drugs, resulting in subtherapeutic concentrations and poorer clinical outcomes when standard dosage guidelines are followed. Objective The aim of this systematic review was to gather and summarise all the available evidence on ARC in critically ill patients, including its definition, underlying mechanisms, epidemiology, diagnosis and impact on both drug pharmacokinetics and clinical outcomes. Method A systematic review was conducted to include all the original studies that provided information on ARC in critically ill patients, and is reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Augmented renal clearance, defined as a creatinine clearance (CrCl)[130 mL/min/1.73 m2, preferably measured in urine, is present in 20–65% of critically ill patients. Younger age, polytrauma and lower severity illness have been identified as risk factors. An influence of ARC on antimicrobial pharmacokinetics has been observed, with ARC consistently being associated with subtherapeutic antibiotic plasma concentrations. Conclusion ARC is a prevalent condition in critically ill patients, especially in young people, with urinary CrCl being the best diagnostic method because mathematical estimates tend to underestimate CrCl. ARC increases renal drug elimination and has a clear influence on certain antimicrobial plasma levels, but is yet to define its impact on clinical outcomes and on pharmacokinetics of other types of drugs. Research on the need to stage ARC and establish specific dosing guidelines is warranted.This study was financially supported by the University of the Basque Country (UPV/EHU) (PPG17/65)

Proteómica redox diferencial: identificación de proteínas oxidadas reversiblemente en respuesta a hipoxia

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Pressurized water extraction of β-glucan enriched fractions with bile acids-binding capacities obtained from edible mushrooms

This is the peer reviewed version of the following article: Biotechnology Progress 30.2 (2014): 391-400, which has been published in final form at http://dx.doi.org/10.1002/btpr.1865.  This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archivingA pressurized water extraction (PWE) method was developed in order to extract β-glucans with bile acids-binding capacities from cultivated mushrooms (Agaricus bisporus, Lentinula edodes and Pleurotus ostreatus) to be used as supplements to design novel foods with hypocholesterolemic properties. Extraction yields were higher in individual than sequential extractions being the optimal extraction parameters: 200ºC, 5 cycles of 5 min each at 10.3 MPa. The crude polysaccharide (PSC) fractions, isolated from the PWE extracts contained mainly β-glucans (including chitooligosaccharides deriving from chitin hydrolysis), -glucans and other PSCs (hetero-/proteo-glucans) depending on the extraction temperature and mushroom strain considered. The observed bile acids-binding capacities of some extracts were similar to a β-glucan enriched fraction obtained from cereals.The research was supported by the European Union within the 7th framework programme (7FM-PEOPLE-2009-IIF project 251285), ALIBIRD-CM S2009/AGR-1469 regional program from the Community of Madrid (Spain) and AGL2010-21537 national R+D program from the Spanish Ministry of Science and Innovation. CTICH is also acknowledged for the cultivation and supplying of the mushrooms fruiting bodie