Objective -Beneficial effects of natural grape polyphenols on human health have been known for a long time and still attract more and more interest of many researchers. The aim of research was to reveal cardioprotective properties of polyphenols contained in grape concentrate "Fenocor" in rats exposed experimental histotoxic hypoxia.Material and Methods -The study was conducted on 21 adult male Wistar rats divided into 3 groups, 2 of which were administered CoCl 2 water solution in 60 mg/kg dose for 7 days. The control group consisted of 5 non-exposed animals. The rats of the second group (n=8) after the administration of cobalt chloride did not receive any treatment, the animals of the third group (n=8) after administration of cobalt chloride were additionally given Fenocor -a grape polyphelols water solution at a dose of 2.5 ml/kg diluted in 0.05 ml of water. Morphological study was performed using light and electron microscopy. During the experiment the following biochemical parameters such as contents of malondialdehyde, oxidative modification of proteins were estimated. Results -The outcome of the cobalt toxic exposure on the heart of animals in experiments resulted in the development of severe cardiomyopathy which lead to the need for timely cardioprotection. Histological structure of myocardium observed in the second group of male rats after cobalt intoxication on the background of grape polyphenol concentrate generally reflected a tendency to minimize of the damage extent which was manifested in the form of normalization of cell structures and muscle fibers. Conclusion -Administration of Fenocor has demonstrated its antioxidant and cytoprotective properties, promoted myocardial structure preservation in rats exposed to histotoxic hypoxia.

BackgroundMexiletine, a class 1b antiarrhythmic medication, appears to have some potential for treating muscle stiffness and other symptoms of myotonias.PurposeThe aim of this study was to analyse the effect and safety of mexiletine on myotonia signs and symptoms in patients with myotonic disorders.Material and methodsA retrospective, observational study including all patients treated with mexiletine at the hospital was carried out.Demographic (age and sex), diagnostic (type of myotonic disorder) and therapeutic (dosage, duration of treatment, previous treatment, adverse reactions) variables were gathered. Statistical analysis of the data was carried out using Microsoft Excel.Results11 patients (10 men and 1 woman, aged 40 (21–56) years) were included from May 2011 to October 2015 (1 patient affected by Schwartz Jampel syndrome, 6 affected by Steinert disease, 1 patient with Thomsen disease and 3 patients with Becker muscular dystrophy).7/11 patients (64%) were taking fenitoine, carbamazepine and/or diuretics before starting mexiletine, with no improvement in their clinical symptoms which led to medication interruption.7/11 patients (64%) are still receiving mexiletine treatment (from 2011, 2012 or 2014). They started treatment at a low dose (100 mg/8–12 h) showing null or insufficient benefits. This dose was increased until achieving a final dose of 200 mg/8 h in all of these patients. All reported experiencing good relief of muscle stiffness in response to mexiletine.4/11 patients (36%) stopped the treatment because they presented low or no improvement in their symptoms. They were treated with doses of 100 mg/8 h or 100 mg/12 h. These doses could not be increased due to patient cardiovascular pathology.91% of patients did not present with any adverse effect. Only one adverse effect (mild upper gastrointestinal pain which disappeared in a few days without interrupting the treatment) was reported in one patient.Conclusion64% of patients treated with mexiletine (all at a dose of 200 mg/8 h) showed improvement in their symptoms and are still under treatment.Mexiletine was well tolerated in all patients, with minor adverse effects in only one patient.Due to the fact that these disorders are rare, the number of patients analysed was low.References and/or AcknowledgementsSpecial acknowledgements to the pharmacy service of my hospital.No conflict of interest.

BackgroundCalprotectin (S100A8/9, MRP8/14) is a promising circulating biomarker reflecting disease activity in patients with rheumatoid arthritis (RA). In two small previous studies in RA patients1,2, serum calprotectin correlated with ultrasound synovial inflammation.ObjectivesTo investigate associations between serum calprotectin, clinical and ultrasound-determined disease activity in a larger cohort of RA patients in a cross-sectional study.MethodsA total of 167 patients with RA (134 females) were enrolled in this study. All patients underwent clinical assessment (SJC, TJC, DAS28-ESR) and ultrasound examination according to the US-7 score3 to assess synovitis by gray-scale (GS) and power Doppler (PD) using semiquantitative grading (0-3). Serum calprotecin was measured by ELISA. Associations between serum calprotectin, C-reactive protein (CRP) and clinical as well as ultrasound findings were explored using Spearman's correlation coefficient. A multiple regression analysis was used to determine the predictive value of calprotectin (mg/l), CRP (mg/l) and DAS28 for GS and PD synovitis score.ResultsSerum calprotectin significantly correlated with DAS28 (r=0.357, p<0.001), SJC (r=0.258, p=0.001), TJC (r=0.181, p<0.05), ESR (r=0.386, p<0.001) and particularly with CRP levels (r=0.540, p<0.001). In addition, calprotectin was also associated with GS (r=0.341, p<0.001) and PD synovitis (r=0.313, p<0.001).Using a multivariate linear regression model with calprotectin, CRP and DAS28-FW as explanatory variables, calprotectin and DAS28, but not CRP, were significant predictors for GS (β=0.371, p<0.001; β=0.598, p<0.001, resp.) and PD synovitis (β=0.346, p<0.001; β=0.379, p<0.001, resp.).ConclusionsThis study confirms in a large cohort of RA patients that serum levels of calprotectin are significantly associated with clinical, laboratory and ultrasound assessments of disease activity. Calprotectin is more closely associated with local joint inflammation than CRP and thus may represent a more specific circulating biomarker for monitoring synovial inflammation in RA patients.ReferencesHammer HB, Fagerhol MK, Wien TN, Kvien TK. The soluble biomarker calprotectin (an S100 protein) is associated to ultrasonographic synovitis scores and is sensitive to change in patients with rheumatoid arthritis treated with adalimumab. Arthritis Res Ther. 2011;13(5):R178.Hurnakova J, Hanova P, Hulejova H, et al. Serum calprotectin (S100A8/9) correlates with clinical and ultrasound outcomes in patients with early rheumatoid arthritis. In Ann Rheum Dis. 2014; Suppl (2):658–658.Backhaus M, Ohrndorf S, Kellner H, Strunk J, Backhaus TM, Hartung W, et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum. 2009 Sep 15; 61(9):1194-1201.AcknowledgementsThis work was supported by the project (Ministry of Health, Czech Republic) for consensual development of research organization 023728, IGA grant No. NT12437 and GAUK grant No. 1010213.Disclosure of InterestNone declared

Estrogen/estrogen receptor-mediated actions play an important role in regulating a variety of biological process including development, homeostasis and breast cancer progression. Even though systemic hormone therapies that either block local estrogen production by aromatase inhibitors (AI) or block actions of estrogen/estrogen receptor (ER) by antiestrogens (AE) is well tolerated, the development of resistance to these agents is still a major concern. Since multiple signaling pathways involved in ER activation, combination of endocrine and non endocrine agents that block these signaling pathways may delay the onset of resistance to hormonal therapy. Recent studies from our laboratory have identified Poly(ADP-ribose) polymerase 4(PARP4) as a novel ER co-regulator. We have investigated with hormone resistant breast cancer cells to demonstrate whether blocking of PARP4 results in resensitization to hormone therapies. PARP comprise of a family of enzymes which catalyses poly(ADPribosyl) action of DNA-binding proteins. PARP-1, the best characterized member, however PARP4 is an understudied protein with numerous capabilities. PARP4 has both N-terminal PXXP and PPXXP motifs which are known to interact with SH3 domain of c-Src as well as LXXLL motif which interacts with estrogen receptor (ER). We show that PARP4 is widely expressed in breast cancer cells (MCF-7, MDA-MB-231, ZR-75, and SKBR3) and its expression is significantly higher in these cells compared to non malignant MCF-10A cells. To understand the important role of PARP4-ER axis in hormonal resistance, metastasis and to test whether blocking of PARP4 mediated actions provide a therapeutic advantage to treat endocrine resistant breast tumors, we have used hormone resistant breast cancer cells that over-express PARP4 or and treated with PARP4 siRNA nanoparticles. The PLGA-siRNA nanoparticles were designed multifunctionally using chemical conjugation. The nanoparticles were characterized physiochemically. Our studies show that PARP4 functionally interacts with ER. As demonstrated by immunoprecipitation, PARP4 interacts with ER upon ligand (E2)-mediated stimulation. PARP4 induces cell cycle progression, local aromatase activity and promotes in vitro tumorigenic potential of breast cancer cells. siRNA nanoparticles of PARP4 inhibit the metastatic incidence in vivo. Our study also shows that PARP4-ER axis enhances multiple signaling cross-talk leading to hormonal independence/resistance and metastasis. Our results suggests that targeting PARP4 may provide a therapeutic advantage to treat endocrine resistant tumors and blocking the development of resistance to hormonal therapeutic agents and as well as decrease the metastatic potential in therapy resistant breast tumors. (Supported by NIH/NCI P30 CA 54174, RRT) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4607.