Investigation of the Antiremodeling Effects of Losartan, Mirabegron and Their Combination on the Development of Doxorubicin-Induced Chronic Cardiotoxicity in a Rat Model

Despite the effectiveness of doxorubicin (DOXO) as a chemotherapeutic agent, dose-dependent development of chronic cardiotoxicity limits its application. The angiotensin-II receptor blocker losartan is commonly used to treat cardiac remodeling of various etiologies. The beta-3 adrenergic receptor agonist mirabegron was reported to improve chronic heart failure. Here we investigated the effects of losartan, mirabegron and their combination on the development of DOXO-induced chronic cardiotoxicity. Male Wistar rats were divided into five groups: (i) control; (ii) DOXO-only; (iii) losartan-treated DOXO; (iv) mirabegron-treated DOXO; (v) losartan plus mirabegron-treated DOXO groups. The treatments started 5 weeks after DOXO administration. At week 8, echocardiography was performed. At week 9, left ventricles were prepared for histology, qRT-PCR, and Western blot measurements. Losartan improved diastolic but not systolic dysfunction and ameliorated SERCA2a repression in our DOXO-induced cardiotoxicity model. The DOXO-induced overexpression of Il1 and Il6 was markedly decreased by losartan and mirabegron. Mirabegron and the combination treatment improved systolic and diastolic dysfunction and significantly decreased overexpression of Smad2 and Smad3 in our DOXO-induced cardiotoxicity model. Only mirabegron reduced DOXO-induced cardiac fibrosis significantly. Mirabegron and its combination with losartan seem to be promising therapeutic tools against DOXO-induced chronic cardiotoxicity.Peer reviewe

7th International Conference on General Inequalities

Inequalities continue to play an essential role in mathematics. The subject is per­ haps the last field that is comprehended and used by mathematicians working in all the areas of the discipline of mathematics. Since the seminal work Inequalities (1934) of Hardy, Littlewood and P6lya mathematicians have laboured to extend and sharpen the earlier classical inequalities. New inequalities are discovered ev­ ery year, some for their intrinsic interest whilst others flow from results obtained in various branches of mathematics. So extensive are these developments that a new mathematical periodical devoted exclusively to inequalities will soon appear; this is the Journal of Inequalities and Applications, to be edited by R. P. Agar­ wal. Nowadays it is difficult to follow all these developments and because of lack of communication between different groups of specialists many results are often rediscovered several times. Surveys of the present state of the art are therefore in­ dispensable not only to mathematicians but to the scientific community at large. The study of inequalities reflects the many and various aspects of mathemat­ ics. There is on the one hand the systematic search for the basic principles and the study of inequalities for their own sake. On the other hand the subject is a source of ingenious ideas and methods that give rise to seemingly elementary but nevertheless serious and challenging problems. There are many applications in a wide variety of fields from mathematical physics to biology and economics

Prevention and contrast of child abuse and neglect in the practice of European paediatricians: a multi-national pilot study

Background: Child abuse and neglect, or maltreatment, is a serious public health problem, which may cause long-term effects on children's health and wellbeing and expose them to further adulthood vulnerabilities. Studies on child maltreatment performed in Europe are scarce, and the number of participants enrolled relatively small. The aim of this multi-national European pilot study, was to evaluate the level of understanding and perception of the concepts of child abuse and neglect by European paediatricians working in different medical settings, and the attitude toward these forms of maltreatment in their practice. Methods: The study was performed by a cross-sectional, descriptive, online survey, made available online to European paediatricians members of 50 national paediatric, who belonged to four different medical settings: hospital, family care, university centres and private practice. The questionnaire, designed as a multiple choice questions survey, with a single answer option consisted of 22 questions/statements. Frequency analyses were applied. Most of the data were described using univariate analysis and Chi-squared tests were used to compare the respondents and answers and a significance level of p ≤ 0.05 applied. Results: Findings show that European paediatricians consider the training on child maltreatment currently provided by medical school curricula and paediatric residency courses to be largely insufficient and continuing education courses were considered of great importance to cover educational gaps. Physical violence was recognized by paediatricians mostly during occasional visits with a significant correlation between detecting abuse during an occasional visit and being a primary care paediatrician. Results also showed a reluctance by paediatricians to report cases of maltreatment to the competent judicial authorities. Conclusions: Data of this study may provide useful contribution to the current limited knowledge about the familiarity of European paediatricians with child maltreatment and their skills to recognize, manage and contrast abusive childhood experiences in their practice. Finally, they could provide local legislators and health authorities with information useful to further improve public health approaches and rules able to effectively address shared risk and protective factors, which could prevent child abuse and neglect from ever occurring