Paraplegia that results from spinal cord ischemia is a catastrophic complication of thoracic and thoracoabdominal aorta surgical procedures. Despite several surgical modifications and pharmacologic approaches, paraplegia has not been totally eliminated. On clinical grounds, the efficiency of currently used pharmacologic agents to prevent spinal cord injury during thoracic and thoracoabdominal aorta surgery is very limited and their benefit is controversial. Preischemic infusion of resveratrol protects the spinal cord from ischemia reperfusion injury in rabbits. Following clarification of the underlying protective mechanism, optimal dose, and timing, resveratrol may used in humans as an adjunct to eliminate this catastrophic complication.

The antioxidant activities of four Lamiaceae plants, Salvia viridis L., Salvia multicaulis Vahl, Stachys byzantina C. Koch and Eremostachys laciniata (L.) Bunge have been determined by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as by flow injection analysis-luminol chemiluminescence (FIA-CL). All extracts were shown to possess a significant scavenger activity against DPPH free radical and an inhibitory effect on H2O2- or HOCl-luminol chemiluminescence. The extracts scavenged 50% of DPPH radical ranging in the following descending order: Salvia viridis > Stachys byzantina > Salvia multicaulis > Eremostachys laciniata. The most potent extract on H2O2-induced peak chemiluminescence was that of Salvia viridis and on HOCl-induced peak chemiluminescence was that of Stachys byzantina. The results concluded that the extracts have a potential source of antioxidants of natural origin.

Background: The turnover of cardiac ion channels underlying action potential duration is regulated by ubiquitination. Genome-wide association studies of QT interval identified several single-nucleotide polymorphisms located in or near genes involved in protein ubiquitination. A genetic variant upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor) gene prompted us to determine its role in modulating cardiac excitation. Methods: Optical mapping was performed in zebrafish hearts to determine Ca 2+ transients. Live-cell confocal calcium imaging was performed on adult rabbit cardiomyocytes to determine intracellular Ca 2+ handling. L-type calcium channel (LTCC) current ( I Ca,L ) was measured using whole-cell recording. To study the effect of LITAF on Cav1.2 (L-type voltage-gated calcium channel 1.2) channel expression, surface biotinylation, and Westerns were performed. LITAF interactions were studied using coimmunoprecipitation and in situ proximity ligation assay. Results: LITAF knockdown in zebrafish resulted in a robust increase in calcium transients. Overexpressed LITAF in 3-week-old rabbit cardiomyocytes resulted in a decrease in I Ca,L and Cavα1c abundance, whereas LITAF knockdown increased I Ca,L and Cavα1c protein. LITAF-overexpressing decreases calcium transients in adult rabbit cardiomyocytes, which was associated with lower Cavα1c levels. In tsA201 cells, overexpressed LITAF downregulated total and surface pools of Cavα1c via increased Cavα1c ubiquitination and its subsequent lysosomal degradation. We observed colocalization between LITAF and LTCC in tsA201 and cardiomyocytes. In tsA201, NEDD ( neural precursor cell expressed developmentally downregulated protein ) 4-1, but not its catalytically inactive form NEDD4-1-C867A, increased Cavα1c ubiquitination. Cavα1c ubiquitination was further increased by coexpressed LITAF and NEDD4-1 but not NEDD4-1-C867A. NEDD4-1 knockdown abolished the negative effect of LITAF on I Ca,L and Cavα1c levels in 3-week-old rabbit cardiomyocytes. Computer simulations demonstrated that a decrease of I Ca,L current associated with LITAF overexpression simultaneously shortened action potential duration and decreased calcium transients in rabbit cardiomyocytes. Conclusions: LITAF acts as an adaptor protein promoting NEDD4-1–mediated ubiquitination and subsequent degradation of LTCC, thereby controlling LTCC membrane levels and function and thus cardiac excitation.

Anthracyclines can cause severe cardiac toxicity leading to heart failure. The aim of this study was to determine the effects of cardioprotective polyphenolic compound resveratrol (RES) and adipose-derived mesenchymal stem cells (ADMSCs) on cardiac tissue of rats treated with doxorubicin (DOX). Forty-two female and three male Wistar-Albino rats were included in the study. The study groups and the control groups were as follows: Group I: DOX; Group II: DOX + RES; Group III: DOX + ADMSCs; Group IV: DOX + RES + ADMSCs; Group V: Sham operation; and Group VI: normal saline. ADMSCs obtained from male rats were defined with stem cell markers [CD11b/c(-), CD45(-), CD90(+), CD44(+), and CD49(+)]. DOX 12 mg/kg intraperitoneally (i.p.) was injected as a single dose in female rats. Resveratrol 100 mg/kg was injected three times i.p. in Groups II and IV. ADMSCs 2 × 10(6) cells/kg/dose were labeled with bromodeoxyuridine (BrdU) and injected i.p. for a total of three times in Groups III and IV. When the study was terminated after 4 weeks, the beating hearts were connected to a Langendorff setup and records were obtained for 30 minutes. Histopathological, immunhistochemical, and immunofluorescent examination with H&E, Troponin I, and BrdU stains were also performed. Also, ADMSCs were demonstrated in the myocardium of transplanted rats. Left ventricle functions and myocardial histology demonstrated significant impairment in DOX only group compared to groups with ADMSCs (P < .05). We suggest that RES and ADMSCs were successful in the prevention and treatment of the doxorubicin cardiomyopathy in rats. The hypothetical mechanisms of regeneration are multiple, including cell differentiation and autocrine/paracrine effects of ADMSCs.