Isolated JUP plakoglobin gene mutation with left ventricular fibrosis in familial arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited disorder usually affecting the right ventricle (RV), characterized by fibro-fatty tissue replacement of the healthy ventricular myocardium. It often predisposes young patients to ventricular tachycardia, heart failure, and/or sudden cardiac death. However, recent studies have suggested predominantly left ventricle (LV) involvement with variable and/or atypical manifestations. Cardiac magnetic resonance (CMR) imaging has emerged as the noninvasive gold standard for the diagnosis of ARVC. CASE SUMMARY: A 21-year-old athletic male with a family history of unknown ventricular arrhythmias, presented with near syncope, chest pain, and exertional palpitations. He had an initial work-up that was grossly unremarkable including an electrocardiogram (ECG), echocardiogram and a CMR study. Six months later, he presented again with recurrent symptoms of presyncope during exercise and his ECG demonstrated new findings of a terminal activation delay in his precordial leads. He had markedly elevated cardiac biomarkers, (troponin I > 100 ng/dl, normal value < 0.04 ng/dl) and demonstrated ventricular tachycardia with a right bundle branch morphology. An endomyocardial biopsy did not reveal any pathology. A follow-up CMR demonstrated the new development and prominent left ventricular epicardial scar in the lateral wall. The patient underwent familial genetic testing, which confirmed the presence of an isolated junction plakoglobin (JUP) gene mutation and showed multiple genes consistent with ARVC in his mother. Thus, he manifested a partial transmission of only one abnormal gene for ARVC and exhibited a markedly different expression in his disease without evidence of typical right-sided heart pathology. A third CMR study was performed, which showed partial improvement in myocardial fibrosis after exercise cessation. CONCLUSION: We present a case of a young athletic male with a newly diagnosed isolated JUP gene mutation and a genetically diagnosed family history of ARVC. During his course, he demonstrated the progression of new, atypical, left ventricular fibrosis. This case demonstrates a complex interplay between genetic penetrance, phenotypical heterogeneity, and lifestyle factors such as exercise in disease progression and provides insight into the natural course of an isolated JUP mutation. Although rare, clinicians should have a high threshold for the clinical suspicion of ARVC or variants of this disorder even in the absence of classic right-sided pathologies.

A novel dietary supplement containing multiple phytochemicals and vitamins elevates hepatorenal and cardiac antioxidant enzymes in the absence of significant serum chemistry and genomic changes.

A novel dietary supplement composed of three well-known phytochemicals, namely, Salvia officinalis (sage) extract, Camellia sinensis (oolong tea) extract, and Paullinia cupana (guarana) extract, and two prominent vitamins (thiamine and niacin) was designed to provide nutritional support by enhancing metabolism and maintaining healthy weight and energy. The present study evaluated the safety of this dietary supplement (STG; S=sage; T=tea; G=guarana) and assessed changes in target organ antioxidant enzymes (liver, kidneys and heart), serum chemistry profiles and organ histopathology in Fisher 344 rats. Adult male and female Fisher 344 rats were fed control (no STG) or STG containing (1X and 7X, 1X=daily human dose) diets and sacrificed after 2 and 4 months. Serum chemistry analysis and histopathological examination of three vital target organs disclosed no adverse influence on protein, lipid and carbohydrate profiles, genomic integrity of the liver and/or the tissue architecture. However, analysis of the most important antioxidant components in the liver, kidney and heart homogenates revealed a dramatic increase in total glutathione concentrations, glutathione peroxidase and superoxide dismutase enzyme activities. Concomitantly, oxidative stress levels (malondialdehyde accumulation) in these three organs were less than control. Organ specific serum markers (ALT/AST for the liver; CPK/AST for the heart; BUN/creatinine for kidneys) and the genomic integrity disclosed no STG-induced alteration. Some of the serum components (lipid and protein) showed insignificant changes. Overall, STG-exposed rats were more active, and the results suggest that STG exposure produces normal serum chemistry coupled with elevated antioxidant capacity in rats fed up to seven times the normal human dose and does not adversely influence any of the vital target organs. Additionally, this study reiterates the potential benefits of exposure to a pharmacologically relevant combination of phytochemicals compared to a single phytochemical entity.

Long term exposure effect of a unique metabolic nutrition system containing a diverse group of phytochemicals on serum chemistry and genomic and non-genomic changes in the liver of female B6C3F1 mice.

The nutritional value and therapeutic benefits coupled with presumed safety have heightened interest in the use of custom designed dietary supplements. Their use has increased substantially since the passage of the 1994 Dietary Supplement Health Education Act. However, few well-controlled studies have been conducted to assess the safety and potential adverse effects of dietary supplements. MNSO (MNS Orange-AdvoCare) is a unique combination of vitamins, minerals, omega-3 fatty acids and herbal extracts designed to provide a strong foundation of nutritional support, enhance thermogenesis, heighten energy levels and improve immune status. This investigation was designed to explore the safety and toxic effects, if any, of 12 months of continuous exposure to the ephedra and caffeine containing MNSO on serum chemistry and histopathology of seven vital target organs in female B6C3F1 mice. MNSO is enriched with extracts of citrus, Ephedra, Ginkgo, green tea and Ocimum. In this study, mice were fed control (-MNSO) or MNSO (1x-10x, 1x = daily human dose) diets. Blood was collected from all groups including the control every 4 months for serum chemistry analysis (enzyme, lipid, carbohydrate, electrolyte profiles), and liver tissue was collected for tissue biochemistry and histopathology. Multiple biochemical parameters included: (i) determination of oxidative stress via lipid peroxidation and (ii) assessment of genomic integrity via DNA fragmentation. In addition, food consumption and body weight changes were also monitored biweekly. The data showed that 12 months ingestion of 10x-MNSO did not significantly influence organ histopathology, alter the normal serum chemistry profile or any of the crucial tissue biochemistry. MNSO-exposed animals were more active, consumed more food and were relatively leaner compared with the controls. This study indicates that a caffeine and ephedra containing metabolic nutrition system is non-toxic and non-hepatotoxic in mice at up to 10x the human consumption dose of ephedra.