Arnold Melman

Albert Einstein College of Medicine, New York, New York, United States

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Publications (213)714.42 Total impact

  • Aryeh Keehn · Moses Tar · Kelvin Davies · Sylvia Suadicani · Arnold Melman ·

    The Journal of Urology 04/2015; 193(4):e77. DOI:10.1016/j.juro.2015.02.280 · 4.47 Impact Factor
  • Yi Wang · Moses T Tar · Shibo Fu · Arnold Melman · Kelvin P Davies ·
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    ABSTRACT: Objectives To investigate the effect of diabetes on urothelial modulation of bladder contractility.Methods Bladder strips (urothelium intact or denuded) were prepared from 8-week-old streptozotocin-induced diabetic (n = 19) and non-diabetic control rats (n = 10). The effect of modulators of MaxiK (iberiotoxin and tetraethylammonium) and Kv7 (XE991 and retigabine) potassium channel activity were investigated for their effects on both carbachol-induced force generation and spontaneous contractile activity.ResultsIn bladder strips from non-diabetic animals, the presence of the urothelium resulted in marked sensitivity to carbachol-induced force generation by modulators of MaxiK and Kv7 channel activity, whereas in the diabetic animal urothelial sensitivity to these agents was significantly diminished. Urothelial-intact bladder strips from non-diabetic animals were more sensitive to modulators of Kv7 activity in reducing the amplitude of spontaneous phasic contractions than urothelial-denuded bladder strips, whereas in diabetic animals the presence or absence of the urothelium did not alter the sensitivity to modulators of Kv7 activity. Spontaneous activity in the presence of tetraethylammonium was not affected by the urothelium in bladder strips from either diabetic or non-diabetic animals.Conclusions The presence of the urothelium in bladders from non-diabetic animals modulates the activity of potassium blockers to affect bladder contractility, whereas in the diabetic bladder this effect is attenuated. These findings could help to explain the lack of success of pharmaceutical treatments targeting potassium channels to treat bladder pathology in patients with diseases imparing urothelial function.
    International Journal of Urology 06/2014; 21(10). DOI:10.1111/iju.12491 · 2.41 Impact Factor
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    Shibo Fu · Moses Tarndie Tar · Arnold Melman · Kelvin Paul Davies ·
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    ABSTRACT: Men with sickle cell disease (SCD) risk developing priapism. Recognizing that SCD is a disease of hypoxia, we investigated the effect of hypoxia on gene expression in corporal smooth muscle (CSM) cells. Rat CSM cells in vitro were treated with CoCl2 or low oxygen tension to mimic hypoxia. Hypoxic conditions increased expression of genes previously associated with priapism in animal models. Variable coding sequence a1 (Vcsa1; the rat opiorphin homologue, sialorphin), hypoxia-inducible factor 1a (Hif-1a), and A2B adenosine receptor (a2br) were increased by 10-, 4-, and 6-fold, respectively, by treatment with CoCl2, whereas low oxygen tension caused increases in expression of 3-, 4-, and 1.5-fold, respectively. Sialorphin-treated CSM cells increased expression of Hif-1a and a2br by 4-fold, and vcsa1-siRNA treatment reduced expression by ∼50%. Using a Hif-1a inhibitor, we demonstrated up-regulation of a2br by sialorphin is dependent on Hif-1a, and knockdown of vcsa1 expression with vcsa1-siRNA demonstrated that hypoxic-up-regulation of Hif-1a is dependent on vcsa1. In CSM from a SCD mouse, there was 15-fold up-regulation of opiorphin at a life stage prior to priapism. We conclude that in CSM, opiorphins are master regulators of the hypoxic response. Opiorphin up-regulation in response to SCD-associated hypoxia activates CSM "relaxant" pathways; excessive activation of these pathways results in priapism.-Fu, S., Tar, M. T., Melman, A., Davies, K. P. Opiorphin is a master regulator of the hypoxic response in corporal smooth muscle cells.
    The FASEB Journal 05/2014; 28(8). DOI:10.1096/fj.13-248708 · 5.04 Impact Factor
  • Yi Wang · Moses Tar · Shibo Fu · Arnold Melman · Kelvin Davies ·

    The Journal of Urology 04/2014; 191(4):e5. DOI:10.1016/j.juro.2014.02.109 · 4.47 Impact Factor
  • Shibo Fu · Moses Tar · Arnold Melman · Yi Wang · Kelvin Davies ·

    The Journal of Urology 04/2014; 191(4):e478. DOI:10.1016/j.juro.2014.02.1161 · 4.47 Impact Factor
  • Yi Wang · Moses Tar · Arnold Melman · Kelvin Davies ·

    The Journal of Urology 04/2013; 189(4):e117. DOI:10.1016/j.juro.2013.02.1671 · 4.47 Impact Factor
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    ABSTRACT: What's known on the subject? and What does the study add? Partial urethral obstruction (PUO), a common urologic pathology in men and children, can be associated with detrusor overactivity (DO), but the exact molecular mechanisms responsible for the altered contractile phenotypes have not been fully elucidated. Our study is the first to determine by direct patch-clamp current measurement that PUO, to recapitulate many of the pathological characteristics of benign prostatic hyperplasia (BPH), is associated with an approximate 5-fold decrease in bladder myocyte Maxi-K channel activity. Similar to others we report a 40% decrease in Maxi-K α subunit expression which correlates with the observed decrease in Maxi-K activity, but uniquely as much as a 5-fold increase in expression of Maxi-K β subunit which we hypothesize may be a compensatory response. Based upon our previous finding of increased detrusor overactivity (DO) in similar male PUO rats, we suggest the Maxi-K channel as a therapeutic target to treat BPH associated lower urinary tract symptoms (LUTS).
    BJU International 04/2012; 110(8 Pt B):E402-8. DOI:10.1111/j.1464-410X.2012.11137.x · 3.53 Impact Factor
  • Yi Wang · Gongyi Ren · Moses Tar · Arnold Melman · Kelvin Davies ·

    The Journal of Urology 04/2012; 187(4):e50. DOI:10.1016/j.juro.2012.02.170 · 4.47 Impact Factor

  • The Journal of Urology 04/2012; 187(4):e330. DOI:10.1016/j.juro.2012.02.896 · 4.47 Impact Factor
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    ABSTRACT: Cycling is associated with genital neuropathies and erectile dysfunction in males. Women riders also have decreased genital sensation; however, sparse information exists addressing the effects of modifiable risks on neurological injuries in females. This study assesses the effects of bicycle setup and cyclists' attributes on GS and saddle pressures among female cyclists. Previously, we compared genital sensation in competitive female cyclists (N = 48) to that of female runners (N = 22). The current study is a subanalysis of the 48 cyclists from the original study group. Nonpregnant, premenopausal women who rode at least 10 miles per week, 4 weeks per month were eligible for participation. Genital sensation was measured in microns using biosthesiometry measures of vibratory thresholds (VTs). Perineal and total saddle pressures were determined using a specialized pressure map and recorded in kilopascals (kPA). Handlebars positioned lower than the saddle correlated with increased perineum saddle pressures and decreased anterior vaginal and left labial genital sensation (P < 0.05, P < 0.02, P < 0.03, respectively). Low handlebars were not associated with total saddle pressures or altered genital sensation in other areas. After adjusting for age and saddle type, low handlebars were associated with a 3.47-kPA increase in mean perineum saddle pressures (P < 0.04) and a 0.86-micron increase in anterior vagina VT (P < 0.01). Handlebars positioned lower than the saddle were significantly associated with increased perineum saddle pressures and decreased genital sensation in female cyclists. Modifying bicycle setup may help alleviate neuropathies in females. Additional research is warranted to further assess the extent of the associations.
    Journal of Sexual Medicine 03/2012; 9(5):1367-73. DOI:10.1111/j.1743-6109.2012.02680.x · 3.15 Impact Factor
  • Steve K Williams · Arnold Melman ·
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    ABSTRACT: Erectile dysfunction (ED) is a neurovascular phenomenon modulated by hormonal, local biochemical, and biomechanical/structural factors of the penis. The success of the orally active phosphodiesterase inhibitors for the treatment of ED has boosted research activities into the physiology of the erectile mechanism. Peripheral intracellular signal transduction in the penis as well as central brain and spinal cord pathways controlling penile erection have been investigated and are now better understood. The results of this ongoing research have provided the basis for the development and introduction of several novel therapeutic modalities into the management of ED. Many novel pharmacotherapeutic approaches under development including the use of melanocortins and Rho-kinase inhibitors as well as the introduction of gene therapy and tissue engineering have demonstrated efficacy in animal as well as early human trials. This review describes the major new and evolving pharmacological advances in the field of oral pharmacotherapy for the treatment of male ED.
    Maturitas 12/2011; 71(1):20-7. DOI:10.1016/j.maturitas.2011.11.004 · 2.94 Impact Factor
  • Xinhua Zhang · Nirmala D Kanika · Arnold Melman · Michael E DiSanto ·
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    ABSTRACT: Diabetes mellitus (DM) is a quite common chronic disease, and the prevalence of erectile dysfunction (ED) is three times higher in this large population. Although diabetes-related ED has been studied extensively, the actin-myosin contractile apparatus was not examined. The mRNAs encoding smooth muscle myosin (SMM) heavy chains (MHC) and essential light chains (LC(17)) exist as several different alternatively spliced isoforms with distinct contractile properties. Recently, we provided novel data that blebbistatin (BLEB), a specific myosin II inhibitor, potently relaxed corpus cavernosum smooth muscle (CCSM). In this study, we examine whether diabetes alters SMM expression, alternative splicing, and/or functional activities, including sensitivity to BLEB. By using streptozotocin (STZ)-induced 2-mo diabetic rats, functional activities were tested in vivo by intracavernous pressure (ICP) recording during cavernous nerve stimulation and in vitro via organ bath contractility studies. SMM isoform composition was analyzed by competitive RT-PCR and total SMM, myocardin, and embryonic SMM (SMemb) expression by real-time RT-PCR. Results revealed that the blood glucose level of STZ rats was 407.0 vs. 129.5 mg/dl (control). STZ rats exhibited ED confirmed by significantly increased CCSM contractile response to phenylephrine and decreased ICP response. For STZ rats, SM-B, LC(17a) and SM2 isoforms, total SMM, and myocardin expression increased, whereas SM-A, LC(17b), and SM1 isoforms were decreased, with SMemb unchanged. BLEB was significantly more effective in relaxing STZ CCSM both in vitro and in vivo. Thus we demonstrated a novel diabetes-specific effect on alternative splicing of the SMM heavy chain and essential light chain genes to a SMM isoform composition favoring a heightened contractility and ED. A switch to a more contractile phenotype was supported further by total SMM expression increase. Moreover, the change in CCSM phenotype was associated with an increased sensitivity to BLEB, which may serve as a novel pharmacotherapy for ED.
    AJP Endocrinology and Metabolism 09/2011; 302(1):E32-42. DOI:10.1152/ajpendo.00231.2011 · 3.79 Impact Factor
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    ABSTRACT: There are numerous genital complaints in women cyclists, including pain, numbness, and edema of pelvic floor structures. Debate ensues about the best saddle design for protection of the pelvic floor. To investigate the relationships between saddle design, seat pressures, and genital nerve function in female, competitive cyclists. We previously compared genital sensation in healthy, premenopausal, competitive women bicyclists and runners. The 48 cyclists from our original study comprise the study group in this subanalysis. Main outcome measures were: (i) genital vibratory thresholds (VTs) determined using the Medoc Vibratory Sensation Analyzer 3000 and (ii) saddle pressures as determined using a specially designed map sensor. More than half of the participants (54.8%) used traditional saddles, and the remainder (45.2%) rode with cut-out saddles. On bivariate analysis, use of traditional saddles was associated with lower mean perineal saddle pressures (MPSP) than riding on cut-out saddles. Peak perineal saddle pressures (PPSP) were also lower; however, the difference did not reach statistical significance. Saddle design did not affect mean or peak total saddle pressures (MTSP, PTSP). Saddle width was significantly associated with PPSP, MTSP, and PTSP but not with MPSP. Women riding cut-out saddles had, on average, a 4 and 11 kPa increase in MPSP and PPSP, respectively, compared with women using traditional saddles (P = 0.008 and P = 0.010), after adjustment for other variables. Use of wider saddles was associated with lower PPSP and MTSP after adjustment. Although an inverse correlation was seen between saddle pressures and VTs on bivariate analysis, these differences were not significant after adjusting for age. Cut-out and narrower saddles negatively affect saddle pressures in female cyclists. Effects of saddle design on pudendal nerve sensory function were not apparent in this cross-sectional analysis. Longitudinal studies evaluating the long-term effects of saddle pressure on the integrity of the pudendal nerve, pelvic floor, and sexual function are warranted.
    Journal of Sexual Medicine 08/2011; 8(11):3144-53. DOI:10.1111/j.1743-6109.2011.02437.x · 3.15 Impact Factor
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    ABSTRACT: The MaxiK potassium channel is regulated by voltage and intracellular calcium, and plays a critical role in regulating intracellular calcium concentration ([Ca(2+) ](i)), which is the ultimate determinant of smooth muscle tone. Tight control of corpus cavernosum smooth muscle (CCSM) tone is critically important and misregulation can result in erectile dysfunction. Because of the tight functional linkage of MaxiK and calcium channel activity, the aim of this study was to determine the effects of silencing and pharmacological inhibition of MaxiK on calcium homeostasis and intercellular calcium signaling in CCSM cells. We compared changes in the basal intracellular [Ca(2+) ](i) and parameters defining intercellular calcium wave (ICW) spread in 48 hours MaxiK silenced CCSM cells vs. acute blockade of the channel with iberiotoxin. To analyze changes occurring in gene expression we performed micro-array analysis following MaxiK silencing for 48 hours. Changes in Fura-2 fluorescence intensities were measured to evaluate basal [Ca(2+) ](i) levels and ICW parameters. Microarray analysis of global gene expression was performed. Forty-eight hours after MaxiK silencing the basal [Ca(2+) ](i) , the ICW amplitude and spread among CCSM cells were not markedly different in silenced compared to mock transfected controls, whereas short-term blockade significantly increased basal [Ca(2+) ](i) level and amplified Ca(2+) signaling among CCSM cells. Micro-array analysis showed that several genes within Ca(2+) homeostasis and smooth muscle tone regulation pathways had significantly altered expression. Our results indicate that while short-term blockade of the MaxiK channel is associated with an increase in basal [Ca(2+) ](i), Ca(2+) homeostasis is restored during the 48 hours period following silencing. We hypothesize that the different pathways regulating [Ca(2+) ](i) and CCSM tone are linked through molecular crosstalk and that their coordinated regulation is part of a compensatory mechanism aimed to maintain Ca(2+) homeostasis and CCSM tone.
    Journal of Sexual Medicine 08/2011; 8(8):2191-204. DOI:10.1111/j.1743-6109.2010.02180.x · 3.15 Impact Factor
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    ABSTRACT: Diabetes results in a myriad of vascular complications, often referred to as diabetic vasculopathy, which encompasses both microvascular [erectile dysfunction (ED), retinopathy, neuropathy, and nephropathy] and macrovascular complications (hypertension, coronary heart disease, and myocardial infarction). In diabetic animals and patients with ED, there is decreased opiorphin or opiorphin-related gene expression in corporal tissue. Both opiorphin and the rat homologous peptide sialorphin are found circulating in the plasma. In the present study, we investigated if diabetes induced changes in plasma sialorphin levels and if changes in these levels could modulate the biochemistry and physiology of vascular smooth muscle. We show that circulating sialorphin levels are reduced in a rat model of type I diabetes. Intracorporal injection of plasmids expressing sialorphin into diabetic rats restores sialorphin levels to those seen in the blood of nondiabetic animals and results in both improved erectile function and blood pressure. Sialorphin modulated the ability of C-type natriuretic peptide to relax both corporal and aortic smooth muscle strips and of bradykinin to regulate intracellular calcium levels in both corporal and aortic smooth muscle cells. We have previously shown that expression of genes encoding opiorphins is increased when erectile function is improved. Our findings thus suggest that by affecting circulating levels of opiorphin-related peptides, proper erectile function is not only an indicator but also a modulator of overall vascular health of a man.
    AJP Heart and Circulatory Physiology 07/2011; 301(4):H1353-9. DOI:10.1152/ajpheart.00383.2011 · 3.84 Impact Factor
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    ABSTRACT: • To investigate the role that oxidative stress plays in the development of diabetic cystopathy. • Comparative gene expression in the bladder of non-diabetic and streptozotocin (STZ)-induced 2-month- old diabetic rats was carried out using microarray analysis. • Evidence of oxidative stress was investigated in the bladder by analyzing glutathione S-transferase activity, lipid peroxidation, and carbonylation and nitrosylation of proteins. • The activity of protein degradation pathways was assessed using Western blot analysis. • Analysis of global gene expression showed that detrusor smooth muscle tissue of STZ-induced diabetes undergoes significant enrichment in targets involved in the production or regulation of reactive oxygen species (P = 1.27 × 10(-10)). The microarray analysis was confirmed by showing that markers of oxidative stress were all significantly increased in the diabetic bladder. • It was hypothesized that the sequelae to oxidative stress would be increased protein damage and apoptosis. • This was confirmed by showing that two key proteins involved in protein degradation (Nedd4 and LC3B) were greatly up-regulated in diabetic bladders compared to controls by 12.2 ± 0.76 and 4.4 ± 1.0-fold, respectively, and the apoptosis inducing protein, BAX, was up-regulated by 6.76 ± 0.76-fold. • Overall, the findings obtained in the present study add to the growing body of evidence showing that diabetic cystopathy is associated with oxidative damage of smooth muscle cells, and results in protein damage and activation of apoptotic pathways that may contribute to a deterioration in bladder function.
    BJU International 05/2011; 107(10):1676-84. DOI:10.1111/j.1464-410X.2010.09655.x · 3.53 Impact Factor
  • Xinhua Zhang · Arnold Melman · Michael DiSanto ·

    The Journal of Urology 04/2011; 185(4). DOI:10.1016/j.juro.2011.02.727 · 4.47 Impact Factor
  • Xinhua Zhang · Arnold Melman · Michael DiSanto ·

    The Journal of Urology 04/2011; 185(4). DOI:10.1016/j.juro.2011.02.721 · 4.47 Impact Factor
  • Xin-Hua Zhang · Arnold Melman · Michael E Disanto ·
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    ABSTRACT: Normal erectile function (EF) involves a coordinated relaxation of the arteries that supply the penis and the corpus cavernosum smooth muscle (CCSM), resulting in expansion of the sinusoids and increased intracavernous pressure. But the CCSM spends the majority of its time in the contracted state which is mediated by norepinephrine released from nerve endings and other vasoconstrictors like endothelins released from the endothelium. These agents cause smooth muscle myosin (SMM) phosphorylation by elevating intracellular calcium. When calcium returns to basal levels, the calcium sensitivity increases and prevents myosin dephosphorylation, which involves the RhoA/Rho-kinase (ROK) mechanism, thus maintaining force. Although mounting evidences demonstrate that androgens have a major influence on EF that is not just centrally mediated, this notion remains quite controversial. To summarize the current knowledge on CCSM contractile pathways, the role they play in modulating EF, and the influence of androgens. The article reviews the literature and contains some previously unpublished data on CCSM contraction signaling including the role that androgens are known to play in modulating these pathways. Data from peer-reviewed publications and previously unpublished observations. In addition to downregulation of many pro-erectile molecular mechanisms, decreased testosterone (T) levels upregulate CCSM contractility, including hyperresponsiveness to α-adrenergic agonists, increased SMM phosphorylation, alteration of SMM isoform composition, activation of RhoA/ROK signaling and modulation of sphingosine-1-phosphate regulation of CCSM tone. Decreased T levels upregulate CCSM contractile signaling. Meanwhile, it downregulates CCSM relaxation pathways synergizing to produce erectile dysfunction (ED). Although some urologists and researchers are still skeptical of the influence of androgens on penile erection, understanding these molecular control mechanisms as well as the influence that androgens have on these pathways should provide new evidence supporting the roles of androgens in EF and enhance the discovery of novel targets for drug development to treat ED.
    Journal of Sexual Medicine 02/2011; 8(7):1865-79. DOI:10.1111/j.1743-6109.2011.02218.x · 3.15 Impact Factor
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    ABSTRACT: OBJECTIVE To investigate the in vitro and in vivo effects of blebbistatin (a small cell-permeable molecule with high affinity and selectivity toward the myosin II contractile molecule) on bladder smooth muscle (SM) contractility, as antimuscarinic therapy is only 65-75% effective in treating overactive bladder (OAB) and is associated with considerable side-effects, with a <25% continuation rate at 1 year. MATERIALS AND METHODS Bladder and aortic strips from adult male rats, and human bladder strips obtained from open prostatectomy, were used for organ-bath studies of blebbistatin. Awake cystometry was also used in rats in both the presence and absence of intravesically delivered blebbistatin. RESULTS Blebbistatin dose-dependently and completely relaxed both KCl- and carbachol-induced rat detrusor and endothelin-1-induced human bladder contraction. Pre-incubation with 10 Âμm blebbistatin attenuated carbachol responsiveness by ≈65% while blocking electrical field stimulation-induced bladder contraction reaching 50% inhibition at 32 Hz. The basal tone and amplitude of spontaneous contraction were also significantly diminished. Urodynamic variables were obviously altered by intravesical infusion with blebbistatin. CONCLUSION Our novel data show that blebbistatin strongly relaxes both rat and human bladder contraction induced by various physiological stimuli. Coupled with our in vivo data showing that nanomole doses of blebbistatin significantly alter urodynamic variables to produce a less active bladder, our results suggest the possibility of intravesically administered blebbistatin binding at myosin II being developed as a therapeutic treatment for OAB via a novel targeting of the SM contractile apparatus.
    BJU International 01/2011; 107(2):310-7. DOI:10.1111/j.1464-410X.2010.09366.x · 3.53 Impact Factor

Publication Stats

4k Citations
714.42 Total Impact Points


  • 1988-2014
    • Albert Einstein College of Medicine
      • Department of Urology
      New York, New York, United States
  • 2011
    • Cooper University Hospital
      Camden, New Jersey, United States
  • 2009
    • Yeshiva University
      New York, New York, United States
  • 2006-2008
    • Wake Forest University
      Winston-Salem, North Carolina, United States
  • 1991-2008
    • Montefiore Medical Center
      • Department of Urology
      New York, New York, United States
  • 1999
    • University of California, Davis
      Davis, California, United States
  • 1993
    • Albert Einstein Medical Center
      Filadelfia, Pennsylvania, United States
  • 1983-1988
    • Beth Israel Medical Center
      • Department of Urology
      New York, New York, United States