A micellar formulation of quercetin prevents cisplatin nephrotoxicity

Producción CientíficaThe antioxidant flavonoid quercetin has been shown to prevent nephrotoxicity in animal models and in a clinical study and is thus a very promising prophylactic candidate under development. Quercetin solubility is very low, which handicaps clinical application. The aim of this work was to study, in rats, the bioavailability and nephroprotective efficacy of a micellar formulation of Pluronic F127-encapsulated quercetin (P-quercetin), with improved hydrosolubility. Intraperitoneal administration of P-quercetin leads to an increased plasma concentration and bioavailability of quercetin compared to the equimolar administration of natural quercetin. Moreover, P-quercetin retains overall nephroprotective properties, and even slightly improves some renal function parameters, when compared to natural quercetin. Specifically, P-quercetin reduced the increment in plasma creatinine (from 3.4 ± 0.5 to 1.2 ± 0.3 mg/dL) and urea (from 490.9 ± 43.8 to 184.1 ± 50.1 mg/dL) and the decrease in creatinine clearance (from 0.08 ± 0.02 to 0.58 ± 0.19 mL/min) induced by the nephrotoxic chemotherapeutic drug cisplatin, and it ameliorated histological evidence of tubular damage. This new formulation with enhanced kinetic and biopharmaceutical properties will allow for further exploration of quercetin as a candidate nephroprotector at lower dosages and by administration routes oriented towards its clinical use.Fundación de Universidades y Enseñanzas Superiores de Castilla y León (FUESCyL) y Banco de Santander - (grant: Ed. 2014– 2015 Desafío UNIV-EMP)Fundación General de la Universidad de Salamanca, Fondo Europeo de Desarrollo Regional (FEDER) y Junta de Castilla y León - (grant: Ed. 2015 Lanzadera TC)Junta de Castilla y León - (grant: VA225U14

Modelling Future Coronary Heart Disease Mortality to 2030 in the British Isles.

OBJECTIVE: Despite rapid declines over the last two decades, coronary heart disease (CHD) mortality rates in the British Isles are still amongst the highest in Europe. This study uses a modelling approach to compare the potential impact of future risk factor scenarios relating to smoking and physical activity levels, dietary salt and saturated fat intakes on future CHD mortality in three countries: Northern Ireland (NI), Republic of Ireland (RoI) and Scotland. METHODS: CHD mortality models previously developed and validated in each country were extended to predict potential reductions in CHD mortality from 2010 (baseline year) to 2030. Risk factor trends data from recent surveys at baseline were used to model alternative future risk factor scenarios: Absolute decreases in (i) smoking prevalence and (ii) physical inactivity rates of up to 15% by 2030; relative decreases in (iii) dietary salt intake of up to 30% by 2030 and (iv) dietary saturated fat of up to 6% by 2030. Probabilistic sensitivity analyses were then conducted. RESULTS: Projected populations in 2030 were 1.3, 3.4 and 3.9 million in NI, RoI and Scotland respectively (adults aged 25-84). In 2030: assuming recent declining mortality trends continue: 15% absolute reductions in smoking could decrease CHD deaths by 5.8-7.2%. 15% absolute reductions in physical inactivity levels could decrease CHD deaths by 3.1-3.6%. Relative reductions in salt intake of 30% could decrease CHD deaths by 5.2-5.6% and a 6% reduction in saturated fat intake might decrease CHD deaths by some 7.8-9.0%. These projections remained stable under a wide range of sensitivity analyses. CONCLUSIONS: Feasible reductions in four cardiovascular risk factors (already achieved elsewhere) could substantially reduce future coronary deaths. More aggressive polices are therefore needed in the British Isles to control tobacco, promote healthy food and increase physical activity

Epidemiology of physical activity in adult Polish population in the second decade of the 21st century. Results of the NATPOL 2011 study

Objectives: The aim of the study was to assess physical activity (PA) level in a representative sample of Polish adults.Materials and Methods: A cross-sectional analysis was performed among 2413 randomly selected individuals (51.5% women) aged 18-79 years, who participated in the Nationwide Study of Occurrence of Risk Factors of Cardiovascular Diseases NATPOL 2011 (March-July 2011). The study procedures consisted of a questionnaire as well as of anthropometric, blood pressure and biochemical measurements. Leisure-time, occupational and commuting PA were assessed by the use of a questionnaire interview. Results: About 48.2% of adults do exercise for at least 30 minutes on most days of a week. About 11% of the respondents declare a sedentary lifestyle. About 26.5% of working population report hard physical work, while sedentary work is reported by 47.6% of the employed participants. Active commuting is declared by 27.3% of working/studying population. About 47.2%, 36.6%, and 15.3% spend 30 min per day, respectively, on this kind of PA. Conclusions: PA level of more than half of Polish adults is still not satisfactory. Promotion of an active lifestyle should concern mainly leisure-time and commuting PA with paying special attention to substantial differences in various socio-demographic groups

Ocena jakości i stabilności przechowalniczej majeranku (ORIGANUM MAJORANA L.) na podstawie właściwości sorpcyjnych

The aim of the study was to assess the quality and stability of the marjoram (Origanum majorana L.) storage using the characteristics of the sorption properties. In the studied products, evaluation of the sorption properties was done by static and dynamic method based on the kinetics and rate of adsorption of water vapor. For mathematical interpretation of running of water vapor sorption isotherms, the BET equation was used, and also the usefulness of GAB, Peleg and Oswin models was shown to describe the obtained adsorption isotherms, basing on the coefficient of determination (R2). On the grounds of the survey, it was found that the national product, more expensive – marjoram I, was characterized by higher quality and storage stability.Celem pracy była ocena jakości i stabilności przechowalniczej majeranku (Origanum majorana L.) z wykorzystaniem charakterystyki właściwości sorpcyjnych. W badanych produktach oceny właściwości sorpcyjnych dokonano metodą statyczną oraz metodą dynamiczną na podstawie przebiegu kinetyki i szybkości procesu adsorpcji pary wodnej. Do matematycznej interpretacji przebiegu izoterm sorpcji pary wodnej zastosowano równanie BET oraz przedstawiono przydatność modeli GAB, Pelega i Oswina do opisu uzyskanych izoterm adsorpcji, opierając się na współczynniku determinacji (R2). Na podstawie przeprowadzonych badań stwierdzono, że wyższą jakością i stabilnością przechowalniczą charakteryzował się produkt krajowy, droższy – majeranek I

Inhibition of PCAF by Anacardic Acid Derivative Leads to Apoptosis and Breaks Resistance to DNA Damage in BCR-ABL-expressing Cells

Acetylation of histones and nonhistone proteins is a posttranslational modification which plays a major role in the regulation of intracellular processes involved in tumorigenesis. It was shown that different acetylation of proteins correlates with development of leukemia. It is proposed that histone acetyltransferases (HATs) are important novel drug targets for leukemia treatment, however data are still not consistent. Our previous data showed that a derivative of anacardic acid - small molecule MG153, which has been designed and synthesized to optimize the HAT inhibitory potency of anacardic acid, is a potent inhibitor of p300/CBP associated factor (PCAF) acetyltransferase. Here we ask whether inhibition of PCAF acetyltransferase with MG153 will show proapoptotic effects in cells expressing BCR-ABL, which show increased PCAF expression and are resistant to apoptosis. We found that inhibition of PCAF decreases proliferation and induces apoptosis, which correlates with loss of the mitochondrial membrane potential and DNA fragmentation. Importantly, cells expressing BCR-ABL are more sensitive to PCAF inhibition compared to parental cells without BCR-ABL. Moreover, inhibition of PCAF in BCR-ABL-expressing cells breaks their resistance to DNA damage-induced cell death. These findings provide direct evidence that targeting the PCAF alone or in combination with DNA-damaging drugs shows cytotoxic effects and should be considered as a prospective therapeutic strategy in chronic myeloid leukemia cells. Moreover, we propose that anacardic acid derivative MG153 is a valuable agent and further studies validating its therapeutic relevance should be performed