Liver cell line derived conditioned medium enhances myofibril organization of primary rat cardiomyocytes

Cardiomyocytes are the fundamental cells of the heart and play an important role in engineering of tissue constructs for regenerative medicine and drug discovery. Therefore, the development of culture conditions that can be used to generate functional cardiomyocytes to form cardiac tissue may be of great interest. In this study, isolated neonatal rat cardiomyocytes were cultured with several culture conditions in vitro and characterized for cell proliferation, myofibril organization, and cardiac functionality by assessing cell morphology, immunocytochemical staining, and time-lapse confocal scanning microscopy. When cardiomyocytes were cultured in liver cell line derived conditioned medium without exogenous growth factors and cytokines, the cell proliferation increased, cell morphology was highly elongated, and subsequent myofibril organization was highly developed. These developed myofibril organization also showed high level of contractibility and synchronization, representing high functionality of cardiomyocytes. Interestingly, many of the known factors in hepatic conditioned medium, such as insulin-like growth factor II (IGFII), macrophage colony-stimulating factor (MCSF), leukemia inhibitory factor (LIF), did not show similar effects as the hepatic conditioned medium, suggesting the possibility of synergistic activity of the several soluble factors or the presence of unknown factors in hepatic conditioned medium. Finally, we demonstrated that our culture system could provide a potentially powerful tool for in vitro cardiac tissue organization and cardiac function study.National Institutes of Health (U.S.) (NIH DE019024)National Institutes of Health (U.S.) (NIH grant HL092836)National Institutes of Health (U.S.) (NIH grant EB007249)Korea Institute of Science and Technology (KIST) (Institutional Program)United States. Army. Corps of Engineer

Characteristics of P wave in Patients with Sinus Rhythm after Maze Operation

Maze operation could alter P wave morphology in electrocardiogram (ECG), which might prevent exact diagnosis of the cardiac rhythm of patients. However, characteristics of P wave in patients with sinus rhythm after the operation have not been elucidated systematically. Consecutive patients who underwent the modified Cox Maze operation from January to December 2007 were enrolled. The standard 12-lead ECG and echocardiography were evaluated in patients who had sinus rhythm at 6 months after the operation. The average axis of P wave was 65±30 degrees. The average amplitude of P wave was less than 0.1 mV in all 12-leads, with highest amplitude in V1. The most common morphology of P wave was monophasic with positive polarity (49%), except aVR lead, which was different from those in patients with enlarged left atrium, characterized by large P-terminal force in the lead V1. There were no significant differences in P-wave characteristics and echocardiographic parameters between patients with LA activity (30.6%) versus without LA activity (69.4%) at 6 months after the operation. In conclusion, the morphology of P wave in patients after Maze operation shows loss of typical ECG pattern of P mitrale: P wave morphology is small in amplitude, monophasic and with positive polarity

Erectile dysfunction and angiographic correlation between coronary artery stenosis and internal iliac-internal pudendal artery stenosis in patients with suspected coronary artery disease: a retrospective study

This study aimed to assess the angiographic correlation between coronary artery stenosis and internal iliac-internal pudendal artery (II-IPA) stenosis and evaluate its association with erectile dysfunction (ED). We reviewed the data of 91 patients who had undergone pelvic angiography (PA) to evaluate II-IPA stenosis and coronary angiography (CAG) due to suspected coronary artery disease. Erectile function (EF) was evaluated using the International Index of Erectile Function before CAG and PA. CAG was performed first, followed by PA of the bilateral II-IPA. Regardless of the location and number of stenosis sites, based on CAG, we categorized the patients into two groups. Patients with a maximum stenosis <50% and ≥50% on CAG were assigned to Group I and Group II, respectively. Then, the EF domain score and the diameter stenosis (DS) of II-IPA were evaluated and compared. Overall, 55 patients comprised Group I, while 36 patients comprised Group II. ED was present in 96.3% and 97.2% of the patients in Group I and II, respectively. There was no statistical difference between the groups in the severity of ED (p = 0.457). PA revealed that 14.5% and 36.1% of patients in Groups I and II had ≥50% stenosis of the II-IPA. The mean DS of II-IPA in Group II was greater than that in Group I (p = 0.017). There was a statistically significant correlation between the degree of coronary artery stenosis and the degree of II-IPA stenosis (r = 0.295, p = 0.005). This study revealed that coronary artery stenosis correlates with II-IPA stenosis. The presence and degree of coronary artery stenosis or II-IPA stenosis indicate the necessity for more active treatment in patients with ED

Development of tricuspid regurgitation late after left-sided valve surgery: a single-center experience with long-term echocardiographic examinations

OBJECTIVES: This study sought to investigate the incidence and identify the predictors of significant tricuspid regurgitation (TR) development long after left-sided valve surgery. METHODS: Of 615 patients who underwent surgery for left-sided valve disease between 1992 and 1995, 335 patients without significant TR who completed at least 5 years of clinical and echocardiographic follow-up were enrolled. Late significant TR development was assessed by echocardiography with a mean follow-up duration of 11.6 +/- 2.1 years. RESULTS: Significant late TR was found in 90 patients (26.9%). Patients with late TR showed an advanced age (47.6 +/- 13.4 vs 44.3 +/- 13.2 years, P = .04), a higher prevalence of preoperative atrial fibrillation (83.3 vs 46.5%, P < .001), a greater left atrial dimension (56.9 +/- 13.2 vs 52.4 +/- 11.5 mm, P = .006), and a higher prevalence of prior valve surgery (40.0 vs 25.3%, P = .01). In addition, late TR occurred more frequently in patients who had undergone mitral valve surgery than in those who did not (93.3 vs 72.2%, P < .001). However, multivariate analysis showed that the presence of preoperative atrial fibrillation (odds ratio 5.37; 95% CI 2.71-10.65; P < .001) was the only independent factor of late TR development. Patients who developed late TR had a lower event-free survival rate than those who did not (P = .03). CONCLUSIONS: The development of significant TR long after left-sided valve surgery is not uncommon with an estimated incidence of 27% and is closely associated with a poor prognosis. The presence of preoperative atrial fibrillation was identified as the only independent predictor of the development of late TR

Anesthetic management of an adult patient with Rett syndrome and limited mouth opening -A case report-

Rett syndrome is a neurological disease that occurs only in females and it manifests with mental retardation, seizures, movement disorders, autistic behavior and abnormal breathing. A 19-year-old female with Rett syndrome underwent ophthalmologic surgery under general anesthesia at our institution. Airway control was difficult due to her limited mouth opening. We recommend that anesthesiologists should have proper knowledge about this disease and the patients to avoid the complications and problems that can be encountered during the perioperative period

The Function of Heterodimeric AP-1 Comprised of c-Jun and c-Fos in Activin Mediated Spemann Organizer Gene Expression

BACKGROUND:Activator protein-1 (AP-1) is a mediator of BMP or FGF signaling during Xenopus embryogenesis. However, specific role of AP-1 in activin signaling has not been elucidated during vertebrate development. METHODOLOGY/PRINCIPAL FINDINGS:We provide new evidence showing that overexpression of heterodimeric AP-1 comprised of c-jun and c-fos (AP-1(c-Jun/c-Fos)) induces the expression of BMP-antagonizing organizer genes (noggin, chordin and goosecoid) that were normally expressed by high dose of activin. AP-1(c-Jun/c-Fos) enhanced the promoter activities of organizer genes but reduced that of PV.1, a BMP4-response gene. A loss of function study clearly demonstrated that AP-1(c-Jun/c-Fos) is required for the activin-induced organizer and neural gene expression. Moreover, physical interaction of AP-1(c-Jun/c-Fos) and Smad3 cooperatively enhanced the transcriptional activity of goosecoid via direct binding on this promoter. Interestingly, Smad3 mutants at c-Jun binding site failed in regulation of organizer genes, indicating that these physical interactions are specifically necessary for the expression of organizer genes. CONCLUSIONS/SIGNIFICANCE:AP-1(c-Jun/c-Fos) plays a specific role in organizer gene expression in downstream of activin signal during early Xenopus embryogenesis

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care