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Biomedical subjects

Irwin Goldstein

Publications and source records attributed to Irwin Goldstein.

At least 19 recordsLinked to original sources
PubMed2004

Binding characteristics of [3H]delta(5)-androstene-3beta,17beta-diol to a nuclear protein in the rabbit vagina.

In this study, we investigated the binding characteristics of [3H]Delta(5)-androstene-3beta,17beta-diol to rabbit vaginal cytosolic and nuclear extracts and in freshly excised intact tissue strips. [3H]delta(5)-Androstene-3beta,17beta-diol bound to a protein(s) in the vaginal nuclear extract with high affinity (K(d)=3-5 nM) and limited capacity (50-100 fmol/mg protein). No specific binding was detected in the cytoplasmic extracts. Competitive binding studies showed that binding of [3H]delta(5)-androstene-3beta,17beta-diol was effectively displaced with unlabeled delta(5)-androstene-3beta,17beta-diol but not with dehydroepiandrosterone, testosterone, dihydrotestosterone, triamcinolone acetonide, or progesterone. However, estradiol at high concentrations partially displaced bound [3H]delta(5)-androstene-3beta,17beta-diol. Incubation of freshly excised vaginal tissue strips with [3H]delta(5)-androstene-3beta,17beta-diol in the absence or presence of excess unlabeled delta(5)-androstene-3beta,17beta-diol for 1h at 37 degrees C resulted in specific binding to a soluble macromolecule in the nuclear KCl extracts. In addition, quantitative measurement of estrogen receptor, androgen receptor and delta(5)-androstene-3beta,17beta-diol binding protein was performed by equilibrium ligand binding assays using extracts of distal vaginal tissue from intact animals or ovariectomized animals treated for 2 weeks with vehicle, estradiol, testosterone, or estradiol plus testosterone. These changes in steroid hormone levels resulted in opposing trends between the estrogen receptor and delta(5)-androstene-3beta,17beta-diol binding protein, suggesting that delta(5)-androstene-3beta,17beta-diol binding protein is regulated differently by the hormonal milieu than the estrogen receptor. These data suggest that rabbit vaginal tissue expresses a novel binding protein which specifically binds delta(5)-androstene-3beta,17beta-diol and is distinct from the androgen and estrogen receptors.

Androstane-3,17-diol↗
PubMed2004

Prevention and treatment of erectile dysfunction using lifestyle changes and dietary supplements: what works and what is worthless, part I.

Clinicians working in urology should adhere to the same guidelines that are observed in cardiovascular medicine when dealing with a patient with ED. A golden opportunity exists to discuss lifestyle changes with any man with or concerned about ED. Providing heart-healthy recommendations to men with minimal to extensive ED may produce a twofold impact: (1) patients may be able to affect the future extent of their disease, and (2) patients may become healthier overall. Patients following a heart-healthy lifestyle after a diagnosis of ED or to prevent ED should enjoy increased quality or quantity of life. The time is more than ripe for patients to understand that heart health is tantamount to erectile health.

Adult↗
PubMed2004

Prevention and treatment of erectile dysfunction using lifestyle changes and dietary supplements: what works and what is worthless, part II.

It seems naïve to believe that some plants or herbs do not contain specific compounds that could benefit patients with ED. Many supplements have not been investigated in a laboratory or clinical research setting before commercial sale, however,which creates a complex situation. If efficacy is or is not demonstrated through adequate research, then the benefit or lack thereof cannot be mentioned on the label. Furthermore, clinicians and the public cannot be made aware of which compounds or supplements are effective because no general standards for sale exist under the current guidelines. Dietary supplements have received a tremendous amount of publicity. The large and growing market for ED treatment seems to have contributed partly to the promotion of numerous supplements and their apparent benefits. Whether these dietary supplements have merit is questionable. Some supplements may produce results opposite to those advertised. Other supplements may be enjoying the benefits of the placebo effect. Because a placebo response of 25% to 50% has been recorded in clinical trials with effective agents, it is understandable that some supplements enjoy financial success despite the limited research espousing their use. If one to two of four individuals or one of three individuals who try a dietary supplement gain some benefit for their ED, the market for these supplements will remain extraordinary. On a larger scale, of 100,000 men who try a supplement, approximately 25,000 to 50,000 will claim some success. The challenge for clinicians is to discuss the placebo response properly and the need for good research before any intervention, especially supplements, can be advocated for general use. Table 2 summarizes some popular ED supplements and general conclusions that can be drawn from clinical investigations. Some dietary supplements may have an active ingredient that benefits patients with certain types of ED. An exciting area of future dietary supplement research is the ability of certain agents to have a synergistic effect with prescription agents for ED, thereby improving response rates in men that have failed approved ED therapy initially, especially with oral agents. Randomized clinical trials are the best method of determining which dietary supplements will become a part of conventional medicine. Therefore, more randomized trials for dietary supplements are needed so that they may have the opportunity to become a part of the mainstream milieu, which means that more funding needs to be made available for ED research. The coming years of research should bring enormous excitement and objectivity to this area of medicine.

Adult↗
PubMed2004

Three-chamber priapism in a patient with primary epithelioid hemangioendothelioma of penis.

A 58-year-old man presented with a 6-month history of painful progressive penile firmness, initially diagnosed as Peyronie's disease. Penile fibrosis involved the entire corpora cavernosa and spongiosum, making it consistent with three-chamber priapism. Cavernosal biopsies revealed epithelioid hemangioendothelioma, and the metastatic workup found hepatic and pulmonary lesions. The patient was treated with paclitaxel, but eventually died of cancer progression. Early infiltrative vascular malignancies of the penis may be indistinguishable from Peyronie's disease. A review of published reports revealed that penile masses associated with progressive growth, obstructive urinary symptoms, dysuria, or painful erections might warrant further evaluation with biopsies.

Antineoplastic Agents, Phytogenic↗
PubMed2004

An in vivo rat model to investigate female vaginal arousal response.

PURPOSE: We established a rat model to investigate the female vaginal arousal response and the role of the nitric oxide (NO) pathway on vaginal blood flow in vivo. MATERIALS AND METHODS: Vaginal blood flow changes induced by pelvic nerve stimulation (PNS) in female Sprague-Dawley rats were determined by laser Doppler flowmetry. Frequency response data were determined in each animal. In addition, changes in vaginal blood flow were measured after intravenous administration of the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) or the phosphodiesterase type 5 inhibitor sildenafil in response to PNS at submaximal frequency. Changes in blood flow were evaluated by comparing the area under the curve of each response. RESULTS: Reproducible frequency dependent increases in vaginal blood flow were observed in response to PNS. Administration of L-NAME (a NO synthase inhibitor) resulted in significant attenuation (25.6% to 18.2% vs control at 30 minutes, p <0.00001) of the PNS induced increase in vaginal blood flow. In contrast, sildenafil administration significantly increased PNS induced vaginal blood flow (166.9% +/- 25.8% vs control at 30 minutes, p <0.00001). CONCLUSIONS: Our data suggest that the rat is a useful and reliable animal model for investigating the vaginal arousal response. In addition, we used this model to demonstrate the important role of the NO-cyclic guanosine monophosphate pathway in vaginal arousal.

Animals↗
PubMed2004

Modulation of rat vaginal blood flow and estrogen receptor by estradiol.

PURPOSE: The effects of subphysiological and physiological levels of estradiol on vaginal blood flow and estrogen receptor were investigated. MATERIALS AND METHODS: Intact or ovariectomized female Sprague-Dawley rats were used. Two weeks after surgery rats were infused with vehicle (polyethyleneglycol), or estradiol at subphysiological (5 microg daily) or physiological (15 microg daily) concentrations for 14 days using osmotic pumps. Changes in vaginal blood flow elicited by pelvic nerve stimulation were assessed by laser Doppler flowmetry. Total levels of functional estrogen receptor were determined by radioligand binding and Western blot analyses were used to assess estrogen receptor (ER) alpha protein. RESULTS: Mean plasma estradiol concentration +/- SEM decreased by 63% in the vehicle group (intact 36.5 +/- 10.3 pg/ml). The subphysiological and physiological estradiol groups had plasma levels that were 55% and 83% of the intact group, respectively. Uterine and vaginal wet weight, and vaginal blood flow were significantly decreased in the vehicle group and normalized by physiological levels of estradiol. However, vaginal blood flow was significantly greater in the subphysiological estradiol group compared to intact animals. Specific binding of [H]estradiol in vaginal tissue extracts from intact rats was 0.51 fmol/mg protein and it was increased 30-fold in the vehicle group. ER binding in vaginal tissue in the physiological estradiol group decreased to levels that were comparable to those in intact animals, whereas estrogen receptor binding remained elevated in the subphysiological estradiol group. These changes were paralleled by ERalpha protein levels. CONCLUSIONS: Estradiol is crucial for maintaining optimal vaginal blood flow in the rat. Lower levels of plasma estradiol trigger compensatory ERalpha up-regulation.

Animals↗
PubMed2003

Selective P2Y2 receptor agonists stimulate vaginal moisture in ovariectomized rabbits.

OBJECTIVE: To determine the expression of P2Y(2) receptors in vaginal and cervical tissues and the effects of P2Y(2) receptor agonists INS45973 and INS365 on vaginal moisture. DESIGN: Pilot in vivo and histological study using animal subjects. SETTING: Experimental laboratory research. ANIMAL(S): Female New Zealand White rabbits were used for in vivo studies and female cynomolgus monkey (Macaca fascicularis) was used for in situ hybridization. INTERVENTION(S): Rabbits were kept intact or ovariectomized. Two weeks after ovariectomy, animals received daily vaginal instillation of vehicle or drugs for 16 days. MAIN OUTCOME MEASURE(S): Vaginal moisture was assessed in rabbits on 4 separate days during the treatment period. The P2Y(2) receptor mRNA distribution was assessed by in situ hybridization of monkey vagina and cervix. RESULT(S): Compared to control, vaginal moisture was significantly diminished in ovariectomized animals treated with vehicle. INS365 (8.1%) and INS45973 (0.9%) increased vaginal moisture in ovariectomized animals to levels that were comparable to or significantly higher than control animals, respectively. In situ hybridization studies indicated that P2Y(2) receptor mRNA was localized to endocervical and cervical gland, epithelium, and stratified squamous epithelium of the vagina. CONCLUSION(S): INS45973 and INS365 may interact with P2Y(2) receptors in the cervix and vagina to stimulate vaginal moisture in the estrogen (E)-deprived state. The P2Y(2) receptor agonists provide a potential nonhormonal alternative for treating vaginal dryness in postmenopausal women.

Animals↗
PubMed2003

Cocaine and ephedrine-induced priapism: case reports and investigation of potential adrenergic mechanisms.

OBJECTIVES: To investigate the direct effect of ephedrine and cocaine on neurogenic contraction of penile trabecular smooth muscle. We also provide three case reports of patients who developed priapism secondary to using either cocaine or nonprescription weight loss formulations containing ephedrine. The use/abuse of cocaine has been associated with priapism. In addition, anecdotal evidence suggests that priapism may result from ephedrine use. However, the effects of cocaine and ephedrine on adrenergic regulation of cavernosal tissue and the potential role of sympathetic dysregulation in the development of priapism have not been studied. METHODS: Isolated rabbit penile cavernosal tissue strips in organ bath preparations were subjected to electrical field stimulation (EFS) at varying frequencies (5 to 40 Hz) in the absence or presence of ephedrine (60 microg/mL) or cocaine (10 microM). Tissues were then subjected to EFS every 30 minutes for up to 20 hours. RESULTS: Ephedrine and cocaine initially caused contractions in cavernosal tissue strips that persisted for several hours. EFS-induced contractions became attenuated over time in tissues treated with ephedrine or cocaine. Eventually, the contractile responses to EFS were not distinguishable from the basal tone, although the tissues remained responsive to exogenous phenylephrine. CONCLUSIONS: Functional activation of alpha-adrenergic receptors on trabecular smooth muscle does not appear to be impaired with prolonged cocaine or ephedrine exposure. However, chronic use of cocaine or ephedrine may deplete norepinephrine from sympathetic nerve terminals, leading to priapism.

Adrenergic alpha-Agonists↗
PubMed2003

Reperfusion of ischemic corporal tissue: physiologic and biochemical changes in an animal model of ischemic priapism.

OBJECTIVES: To assess the physiologic and biochemical changes resulting from ischemia and reperfusion. Effective therapy for ischemic priapism reestablishes corporal venous outflow and arterial inflow and results in increased corporal partial pressure of oxygen. Data are limited concerning reperfusion injury of ischemic erectile tissue associated with reactive oxygen species (ROS) and the potential role of ROS scavengers in the clinical therapy of ischemic priapism. METHODS: Anesthetized adult New Zealand white male rabbits (n = 7) were exposed to a low oxygen tension breathing gas to achieve hypoxia within the corpora cavernosa. This resulted in a mean systemic oxygen saturation of 60%. The pelvic nerve was electrically stimulated to induce penile erection, and the base of the erect penis was clamped. After varying durations of ischemia, the clamp was removed to allow reperfusion. We determined the intracavernosal oxygen tension, histologic changes, myeloperoxidase activity, and lipid peroxidation. RESULTS: Corporal partial pressure of oxygen progressively decreased as the duration of priapism increased. A statistically significant increase was noted in myeloperoxidase activity and lipid peroxidation with corporal reperfusion. Polymorphonuclear leukocyte infiltration was documented in the ischemic reperfused tissue. CONCLUSIONS: In the management of ischemic priapism, reperfusion causes erectile tissue injury owing to the presence of ROS. There is a need to investigate the utility of ROS scavengers and antioxidants in the management of ischemic priapism.

Animals↗
PubMed2003

Effects of ovariectomy and estrogen replacement on basal and pelvic nerve stimulated vaginal lubrication in an animal model.

The goal of this study was to investigate the effects of ovariectomy and estrogen replacement on vaginal tissue integrity and vaginal lubrication in basal conditions and in response to pelvic nerve stimulation (PNS). Two weeks after ovariectomy, female New Zealand White rabbits were administered vehicle or estradiol (200 micrograms/day) for an additional 2 weeks. Ovariectomy caused significant vaginal atrophy and diminished vaginal lubrication in the basal state and after PNS, compared to intact controls. Estrogen replacement normalized lubrication values and tissue wet weight to control levels. In conclusion, vaginal tissue integrity and lubrication are diminished by ovariectomy and are normalized by estrogen replacement.

Animals↗
PubMed2003

A prospective duplex Doppler ultrasonographic study in women with sexual arousal disorder to objectively assess genital engorgement induced by EROS therapy.

The EROS therapy device is FDA-approved for the treatment of women with sexual dysfunction and has been shown to improve sexual function and satisfaction. The aim of this study was to obtain objective information regarding the ability of the EROS Therapy device to induce clitoral and corpus spongiosum volumetric and hemodynamic changes following therapeutic use in women with sexual arousal disorder. Seven patients with sexual arousal disorder formed the study population. All seven subjects met inclusion and exclusion criteria, including having normal hormonal values at the time of the study. All seven subjects were able to comfortably operate the device. All seven reported either slight-to-moderate pleasure or orgasm at home with the device. We observed no adverse events. This study shows that EROS therapy is associated with significant increases in clitoral and corpus spongiosum diameter as well as with clitoral and corpus spongiosum peak systolic and end-diastolic velocity values.

Adult↗