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Tsumagari K.,Human Genetics and Tulane Cancer Center | Baribault C.,Tulane University | Terragni J.,New England Biolabs | Varley K.E.,HudsonAlpha Institute for Biotechnology | And 9 more authors.

Myogenic cell cultures derived from muscle biopsies are excellent models for human cell differentiation. We report the first comprehensive analysis of myogenesis-specific DNA hyper-and hypo-methylation throughout the genome for human muscle progenitor cells (both myoblasts and myotubes) and skeletal muscle tissue vs. 30 non-muscle samples using reduced representation bisulfite sequencing. We also focused on four genes with extensive hyper-or hypo-methylation in the muscle lineage (PAX3, TBX1, MYH7B/MIR499 and OBSCN) to compare DNA methylation, DNaseI hypersensitivity, histone modification, and CTCF binding profiles. We found that myogenic hypermethylation was strongly associated with homeobox or T-box genes and muscle hypomethylation with contractile fiber genes. Nonetheless, there was no simple relationship between differential gene expression and myogenic differential methylation, rather only for subsets of these genes, such as contractile fiber genes. Skeletal muscle retained ~30% of the hypomethylated sites but only ~3% of hypermethylated sites seen in myogenic progenitor cells. By enzymatic assays, skeletal muscle was 2-fold enriched globally in genomic 5-hydroxymethylcytosine (5-hmC) vs. myoblasts or myotubes and was the only sample type enriched in 5-hmC at tested myogenic hypermethylated sites in PAX3/CCDC140 and TBX1. TET1 and TET2 RNAs, which are involved in generation of 5-hmC and DNA demethylation, were strongly upregulated in myoblasts and myotubes. Our findings implicate de novo methylation predominantly before the myoblast stage and demethylation before and after the myotube stage in control of transcription and co-transcriptional RNA processing. They also suggest that, in muscle, TET1 or TET2 are involved in active demethylation and in formation of stable 5-hmC residues. © 2013 Landes Bioscience. Source

Yilmaz D.,Ankara University | Bayatli N.,Ankara University | Un O.,Ankara University | Kadowitz P.J.,Tulane Health science Center | And 3 more authors.

Objective To determine the effect of avanafil, a novel phosphodiesterase-5 inhibitor, on the treatment of erectile dysfunction associated with type 2 diabetes mellitus (T2DM). Methods In 2-day-old rats, T2DM was induced by single intraperitoneal injection of 90 mg/kg of streptozotocin (STZ; i.p.). Erectile responses were evaluated after 10 weeks on intracavernosal injection of avanafil (1 μM) to anesthetized rats and data expressed as intracavernosal pressure (ICP)/mean arterial pressure and total ICP. The relaxant and contractile responses of corpus cavernosum (CC) strips were obtained in vitro studies. Results ICP/mean arterial pressure and total ICP responses were significantly reduced in T2DM rats compared with controls. Avanafil partially restored diminished ICP responses in diabetic rats. In CC strips from the diabetic group, electrical field stimulation (1-20 Hz)-induced relaxation responses were markedly enhanced by 45%, whereas acetylcholine (ACh; 10-8-10 -3)-induced relaxation responses were diminished by 73%. In addition, phenylephrine (PE; 10-8-10-3) and electrical field stimulation (1-40 Hz)-induced contractile responses were significantly reduced in the diabetic group compared with controls. CC relaxant responses to sodium nitroprusside (SNP, 10-8-10-3) and avanafil (10 -8-10-3) were unaltered in both groups. Conclusion The cavernous injection of avanafil in T2DM rats resulted in partial improvement in erectile responses. These findings suggest that intracavernosal administration of avanafil might be beneficial for the treatment of erectile dysfunction in patients with T2DM. © 2014 Published by Elsevier Inc. Source

Liu A.,Ford Motor Company | Carruthers A.,University of British Columbia | Cohen J.L.,AboutSkin Dermatology and DermSurgery | Coleman III W.P.,Tulane Health science Center | And 3 more authors.
Journal of the American Academy of Dermatology

Background: Current guidelines from the Centers for Disease Control and Prevention (CDC) regarding the reconstitution and storage of botulinum toxin type A (BT-A) differ from those of the Centers for Medicare and Medicaid Services and current clinical practice. CDC guidelines require single-patient use of BT-A vials. Strict adherence to these guidelines creates waste and a significant financial impediment, and does not confer increased protection from infection, assuming standard safe injection practices are followed. Objective: This study examines current clinical practices and provides expert consensus recommendations regarding the reconstitution and storage of BT-A. A review of the literature on the sterility and efficacy of BT-A stored beyond the recommended time period of 4 hours is also presented. Methods: An Internet-based survey was used to analyze the current practices of physician members of the American Society for Dermatologic Surgery who administer botulinum type A toxins. Results: After reconstitution, the majority of physicians (68.6%) routinely store BT-A for a period of greater than 1 week and safely use each toxin vial for more than one patient. Not a single case of infection was observed. Limitations: This was a single survey with a 32.2% response rate. Conclusion: A single vial of BT-A can be safely administered to multiple patients, assuming standard safe injection techniques are followed. After reconstitution, Our data suggest that BT-A can be stored beyond the recommended time period of 4 hours. © 2011 by the American Academy of Dermatology, Inc. Source

Pinsky M.R.,Tulane Health science Center | Hellstrom W.J.G.,Tulane University
Therapeutic Advances in Urology

Male hypogonadism, or testosterone deficiency syndrome (TDS), results from a failure of the testes to produce adequate androgen. Patients have low circulating testosterone in combination with clinical symptoms such as fatigue, erectile dysfunction, and body composition changes. The cause may be primary (genetic anomaly, Klinefelter's syndrome) or secondary (defect in hypothalamus or pituitary), but often presents with the same symptomatology. In the older patient, androgen deficiency of the aging male (ADAM) is an important cause of secondary hypogonadism because testosterone levels decline progressively after age 40. Hypogonadal patients have alterations not only in sexual function and body composition, but also in cognition and metabolism. Regardless of etiology, hypogonadal patients who are both symptomatic and who have clinically significant alterations in laboratory values are candidates for treatment. The goal of hormone replacement therapy in these men is to restore hormone levels to the normal range and to alleviate symptoms suggestive of hormone deficiency. This can be accomplished in a variety of ways, although most commonly testosterone replacement therapy (TRT) is employed. © The Author(s), 2010. Source

Langsdon P.R.,University of Tennessee Health Science Center | Rajan R.,Johns Hopkins University | Metzinger S.E.,Tulane Health science Center
Aesthetic Surgery Journal

Background: Brow droop, eyelid tissue excess, and hyperfunction of the muscles of forehead facial expression may contribute to the aging diathesis of the upper one-third of the face. Many approaches to the brow have been described, including coronal or pretricheal incisions, direct incision of the suprabrow or forehead, and endoscopic techniques. A less frequent technique, the transblepharoplasty browlift (TBBL), has a role in rejuvenating brow position, especially in patients in whom both the eyelids and brows need to be addressed. The Endotine forehead device has been reported to increase speed and ease in providing operative support to the brows, but little has been written about its function with the TBBL approach. Objectives: The authors describe their results with Endotine brow fixation for browlift through a TBBL approach. Methods: Between November 2005 and January 2008, 20 patients presented to the senior author (PRL) for browlift and were treated with a TBBL approach and placement of the Endotine device in one of three sizes (3 mm, 3.5 mm, or 4 mm). The surgeon completed an operative questionnaire immediately postoperatively, as well as a satisfaction questionnaire at one and three months postoperatively. Nineteen of the 20 patients were followed up also completed satisfaction questionnaires at one and three postoperative months. The results were tabulated to assess the safety and efficacy of the Endotine device. Results: A 3-mm Endotine browlift device was placed in most patients (13; 68%). The surgeon was satisfied with the performance of the Endotine device, its ease of insertion, and the fixation provided in all cases. The Endotine was always palpable under the skin but visible in only roughly half of patients. At one month, 5% of the fixations were judged by the surgeon to be fair in appearance; the remainder of cases were satisfactory or better. At three months, all fixations were judged as satisfactory or better. Patients reported being very satisfied with the results of the surgery initially (53%), and satisfaction improved with time (74%). After three months, 79% of patients would recommend the procedure to others, an increase from 63% after one month. Conclusions: The Endotine device provides an effective lift for the brows, allows for easy repositioning, and is much quicker to apply than the sutures placed in a traditional browlift. © 2010 The American Society for Aesthetic Plastic Surgery, Inc. Source

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