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Stem cell therapy for the treatment of Leydig cell dysfunction in primary hypogonadism

World journal of Stem Cells 2016年第10期8卷 306-315页

作者： Taylor C Peak Nora M Haney William Wang Kenneth j DeLay wayne j hellstrom Department of Urology School of MedicineTulane University

The production of testosterone occurs within the Leydig cells of the testes. When production fails at this level from either congenital, acquired, or systemic disorders,the result is primary hypogonadism. While numerous testosterone formulations have been developed, none are yet fully capable of replicating the physiological patterns of testosterone secretion. Multiple stem cell therapies to restore androgenic function of the testes are under investigation. Leydig cells derived from bone marrow, adipose tissue, umbilical cord, and the testes have shown promise for future therapy for primary hypogonadism. In particular, the discovery and utilization of a group of progenitor stem cells within the testes, known as stem Leydig cells(SLCs), has led not only to a better understanding of testicular development, but of treatment as well. When combining this with an understanding of the mechanisms that lead to Leydig cell dysfunction, researchers and physicians will be able to develop stem cell therapies that target the specific step in the steroidogenic process that is deficient. The current preclinical studies highlight the complex nature of regenerating this steroidogenic process and the problems remain unresolved. In summary, there appears to be two current directions for stem cell therapy in male primary hypogonadism. The first method involves differentiating adult Leydig cells from stem cells of various origins from bone marrow, adipose, or embryonic sources. The second method involves isolating, identifying, and transplanting stem Leydig cells into testicular tissue. Theoretically, in-vivo re-activation of SLCs in men with primary hypogonadism due to age would be another alternative method to treat hypogonadism while eliminating the need for transplantation.

关键词： Stem cell therapy Leydig cells Primary hypogonadism Stem Leydig cells Testosterone Bone marrow-derived stem cells Adipose-derived mesenchymal stem cells

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Purinergic contraction of the rat vas deferens in L-NAME-induced hypertension：effect of sildenafil

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Asian journal of Andrology 2010年第3期12卷 415-421,I0012页

作者： Serap Gur Suresh C. Sikka Gillian E. Knight Geoffrey Bumstock wayne j.G. hellstrom Department of Urology Tulane University Health Sciences Center New Orleans LA 70112 USA Autonomic Neuroscience Centre Royal Free and University College Medical School Rowland Hill Street London NW32PF UK

Hypertension （HTN） is a risk factor for erectile dysfunction, but its effect on vas deferens （VD） contractility and the ejaculatory response has not been delineated. NG-nitro-L-arginine methyl ester （L-NAME）, a nitric oxide synthase inhibitor, was used for induction of nitric oxide （NO）-deficient HTN. Our aim was to evaluate the effects of L-NAME-induced HTN on rat VD contractility and to determine whether sildenafil affects VD contractility. A total of 36 male rats were divided into （1） control, （2）L-NAME-HTN, （3） sildenafil treated L-NAME-HTN groups. Group 2 was treated with L-NAME （40 mg kgI per day） in drinking water for 4 weeks. Group 3 received sildenafil （1.5 mg kg^-1 per day, by oral gavage） concomitantly with L-NAME. The prostatic portion of the VD was subjected to electrical field stimulation （EFS, 1-20 Hz）, and the P2X1 agonist α,β-methylene ATP （α,β meATP, 100 μmol L^-1-1 μmol L-1） and the al-adrenoceptor agonist phenylephrine （Phe, 100 μmol L^-1-1 mmol L^-1） were used to construct concentration-response curves. These experiments were repeated in the presence of P2X receptor antagonist, pyridoxalphosphate-6-azophenyl-2＇,4＇-disulfonic acid （PPADS, 30 μmol L-1）. VD contractions in response to EFS, a,β-meATP and Phe were significantly enhanced by L-NAME. Sildenafil treatment in the L-NAME group improved the contractile response of VD to EFS （20 Hz）. In the presence of PPADS, the enhanced contractile response of VD to EFS and a,β-meATP in hypertensive rats was reversed. In the rat model of chronic NO depletion, the purinergic and adrenergic components and EFS affect VD contractility. The VD contractile response may be mediated more by the purinergic system than the adrenergic system, and sildenafil may alter the ejaculatory response in men with PE.

关键词： hypertensive rat NG-nitro-L-arginine methyl ester purinergic receptors P2X sildenafil vas deferens

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comparative evaluation of semen parameters in pre-and post-Hurricane Katrina human population

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Asian journal of Andrology 2015年第4期17卷 676-680页

作者： Caner Baran wayne j hellstrom Suresh C Sikka Department of Urology Tulane University School of Medicine New Orleans LA 70112 USA.

A natural disaster leading to accumulation of environmental contaminants may have substantial effects on the male reproductive system. Our aim was to compare and assess semen parameters in a normospermic population residing in the Southern Louisiana, USA area pre- and post-Hurricane Katrina. We retrospectively evaluated semen analyses data （n = 3452） of 1855 patients who attended the Tulane University Andrology/Fertility Clinic between 1999 and 2013. The study inclusion criteria were men whose semen analyses showed -〉 1.5 ml volume; _〉15 million ml1 sperm concentration; _〉39 million total sperm count; _〉40% motility; 〉30% morphology, with an abstinence interval of 2-7 days. After the inclusion criteria applied to the population, 367 normospermic patients were included in the study. Descriptive statistics and group-based analyses were performed to interpret the differences between the pre-Katrina （Group 1, 1999-2005） and the post-Katrina （Group 2, 2006-2013） populations. There were significant differences in motility, morphology, number of white blood cell, immature germ cell count, pH and presence of sperm agglutination, but surprisingly there were no significant differences in sperm count between the two populations. This long-term comparative analysis further documents that a major natural disaster with its accompanied environmental issues can influence certain semen oarameters （e.g.. motility and morphology） and, bv extension, fertility potential of the population of such areas.

关键词： environment Hurricane Katrina, New Orleans area normospermic infertile population retrospective semen analYSiS

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Evaluation of corporal fibrosis in cadaveric pericardium and vein grafts for tunica albuginea substitution in rats

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Asian journal of Andrology 2003年第4期5卷 295-299页

作者： Somboon Leungwattanakij Vaewvadee Tiewthanom wayne j.G. hellstrom Department of Urology Ramathibodi Hospital Mahidol University Bangkok 10400 ThailandDepartment of Nursing Ramathibodi Hospital Mahidol University Bangkok 10400 ThailandDepartment of Urology Tulane University Health Sciences Center New Orleans Louisiana USA

Abstract Aim: To evaluate the degree of corporal fibrosis in rats with cadaveric pericardium or vein as grafting materials for tunica albuginea substitution. Materials and methods: Thirty male Sprague-Dawley rats (300 g-325 g) were divided at random into 3 groups of 10 animals each: group 1 was the sham-operated controls and groups 2 and 3 underwent wedge excision of tunica albuginea and replacement with cadaveric pericardium and vein grafts, respectively. Four months later, rats were sacrificed and the penis removed to assess the degree of fibrosis using RT PCR technique for TGP-β1 mRNA expression. The tissues were fixed in 10 % formalin, paraffin-embedded and stained with Masson's trichrome and Verhoff's van Giesen for collagen and elastic fibers. Results: Four months after grafting, there was minimal fibrosis surrounding the patch in the vein graft rats and moderate fibrosis in the pericardial graft rats. The degree of penile fibrosis in the pericardial graft rats was significantly higher than that in the controls (P0.05). Conclusion: The degree of penile fibrosis of cadaveric pericardial graft was significantly higher than that of the control group, while in the vein graft group it was comparable to the latter. The authors believe that the vein graft may be a more ideal substance to be used as the tunica albuginea substitute than the pericardial graft in the surgical treatment of Peyronie's disease.

关键词： Peyronie's disease pericardial graft vein graft

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Prosthetic urology:past,present,and future

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Asian journal of Andrology 2020年第1期22卷 1-1页

作者： Peter N Tsambarlis wayne j G hellstrom Department of Urology Tulane University Medical CenterNew OrleansLA 70112USA

The global population is collectively getting older,and age is directly correlated with erectile dysfunction(ED).With the advent of effective oral agents and wide availability of the Internet,a larger portion of the p... 详细信息

关键词： collective becoming treatment

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Does erectile dysfunction drug use contribute to risky sexual behavior？

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Asian journal of Andrology 2010年第5期12卷 626-627页

作者： wayne j. G. hellstrom Tulane University Health Sciences Center New Orleans LA 70112 USA

Erectile dysfunction （ED） is a common sexual problem affecting up to one-third of men throughout their lives. According to the Massachusetts Male Aging Study （MMAS）, ED affects an estimated 52% of men between the ages of 40 and 70. With the approval of sildenafil （USA in March 1998）, the first phosphodiesterase type 5 （PDE-5） inhibitor to be made available for treatment of ED, and the subsequent approval of vardenafil （USA in August 2003） and tadalafil （USA in November 2003）, the PDE-5 inhibitor class of drugs has rapidly become the first-line therapy for ED of varying etiologies and severities.

关键词： Elderly Silver USA Aging Men

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Premature ejaculation： current and future treatments

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Asian journal of Andrology 2008年第1期10卷 102-109页

作者： Levent Gurkan Matthew Oommen wayne j. G. hellstrom Section of Andrology Department of Urology Tulane University Health Sciences Center New Orleans LA 70112 USA

Premature ejaculation （PE） is recognized to be the most common male sexual disorder. PE provides difficulties for professionals who treat this condition because there is neither a universally accepted definition nor a medication approved by the Food and Drug Administration （FDA）. Despite these shortcomings, physicians continue to diagnose their patients with PE according to major guidelines and treat them with either behavioral therapies or off-label medications. This review focuses on current and emerging treatment options and medications for PE. Advantages and limitations of each treatment option are discussed in the light of current published peer-reviewed literature.

关键词： premature ejaculation male sexual disorder ejaculation

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Men＇s health is evolving

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Asian journal of Andrology 2008年第1期10卷 3-5页

作者： Run Wang wayne j. G. hellstrom Departments of Urology University of Texas Medical School at Houston and University of Texas MD Anderson Cancer Center Houston USA

The Asian journal of Andrology （AjA） is growing at a fast pace and becoming one of the leading journals in the field of andrology thanks to the leadership of Prof. Yi-Fei Wang, Editor-in-Chief of AjA, and the hard work of the AjA editorial staff. It was the spring of 2006 in Chicago when Ms. Dan-Qing Ren, Scientific Editor of the AjA, first approached us at the 31 st American Society of Andrology （ASA） Annual Meeting regarding publishing a special issue on men＇s health. We were honored by the invitation to be guest editors for this special issue. We discussed potential topics with many of the contributors while Ms. Qin-Zhu Zheng, Editorial Director of the AjA worked out the details and met with us at the 32nd ASA Annual Meeting in Tampa, Florida. We are very pleased to present this issue of superior articles with contributions by internationally recognized authorities.

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A comparison of effects of systemic and intratympanic steroid therapies for sudden sensorineural hearing loss:A meta-analysis

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journal of Otology 2016年第1期11卷 18-23页

作者： Dan Zhao Busheng Tong Qiang Wang Sten hellstrom Maoli Duan Department of Otorhinolaryngology-Head and Neck Surgery The First Affiliated Hospital of Anhui Medical University Department of Audiology and Neurotology Department of Clinical Science Intervention and Technology Karolinska Institute

Objective:To evaluate the efficacy and safety of intratympanic and systemic steroid therapies in the initial treatment of Sudden Sensorineural Hearing Loss (SSNHL) patients. Methods:A comprehensive search of PubMed, Wanfang database and CNKI (China National Knowledge Infrastructure) was performed covering the period from january 1990 to july 2014. A meta-analysis was conducted after filtering by the criteria of Cochrane Collaboration. Three hundred fifty six subjects in nine studies allocated to the group of intratympanic steroid therapies and 343 controls receiving systemic steroid therapies met the criteria for meta-analysis. The data were extracted and analyzed using the RevMan 5.3 meta-analysis software. Results: The total effectiveness rate in SSNHL patients receiving intratympanic steroid therapies did not differ statistically from patients receiving systemic therapies (RR ? 1.08, 95%CI ? 0.99e1.99, P ? 0.10), although the rate of full hearing recovery in this group differed significantly from patients receiving systemic therapies (RR ? 1.29, 95%CI ? 1.00e1.66, P ? 0.05). Conclusion: Local steroid therapy appears to generate higher rate of complete hearing recovery than systemic steroid treatment as an initial treatment for SSNHL, which may be especially useful for patients in whom systemic steroids are contraindicated.

关键词： Sudden sensorineural hearing loss Intratympanic steroids Systemic steroid Meta-analysis

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Turbulent Modulation in Particulate Flow: A Review of Critical Variables

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Engineering（科研） 2015年第10期7卷 597-609页

作者： Ammar Saber T.Staffan Lundstrom j.Gunnar I.hellstrom Fluid and Experimental Mechanics Division Lulea University of TechnologyLuleaSweden Mechanical Engineering Department University of MosulMosulIraq

A review of the main mechanisms influencing turbulent modulation in the presence of spherical and non-spherical particles is presented. The review demonstrates the need for more numerical and experimental work with higher accuracy than obtained so far and the need to resolve the flow near the surface of particles with the aim to re-evaluate the quantitative effect of different parameters on turbulent modulation. The review reveals that non-spherical particles have more adverse effect on turbulence as compared to spherical ones, for the same ambient conditions.

关键词： Two Phase Flow Turbulent Modulation Non-Spherical Particle Stokes Number Particle Reynolds Number Length Scale Density Ratio

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