Possibility of inhibition of calcium-activated chloride channel rescuing erectile failures in diabetes.

Although calcium-activated chloride channel (CaCC) blockers, niflumic acid (NFA) and anthracene-9-carboxylic acid (A9C), have been shown as potential erectogenic agents in healthy corpus cavernosum (CC) tissues, the pharmacological characteristics of CaCC blockers in diabetic state are relatively unknown. This study compares the direct muscle relaxant property of NFA and A9C with their influence on contraction and nitrergic relaxation as elicited by electrical field stimulation in normal and 16-week-old diabetic rabbit CC (n=8). Mean blood glucose level in alloxan-treated rabbits was elevated threefold (21.9±0.5 mmol l(-1) vs 7.1±0.2 mmol l(-1) in untreated rabbits; P<0.05). There was no significant alteration in the efficacies of NFA and A9C in eliciting a concentration-dependent relaxation of noradrenaline-induced cavernosum tone and in inhibiting neurogenic contraction of CC from diabetic rabbits. The capability of NFA (100 µM) and A9C (1 mM) in augmenting nitrergic transmission was also not adversely affected by diabetes. However, in CC from diabetic rabbits, A9C markedly increased nitrergic relaxation response to 1-10 Hz by 10.6-36.6% (vs -5.1-0.8% in nondiabetic control). CaCC sensitivity to A9C appears to be enhanced in diabetic CC tissue. Inhibiting the CaCC activity in diabetes-related ED may tip the balance between proerectile/relaxant and antierectile/contractile mechanisms in favor of cavernosum relaxation.

Calcium-activated chloride channels in the corpus cavernosum: recent developments and future of a key cellular component of the erectile process.

Calcium-activated chloride channels (CaCCs) are one of five families of chloride channels, ubiquitously expressed, and essential for a host of biological actions. CaCCs have key roles in processes as diverse as olfactory transduction and epithelial secretion, and also CaCCs are essential in smooth muscle contraction. The corpus cavernosum is a vascular smooth muscle that must relax to facilitate erections. Parasympathetic activation produces relaxation of the corpus cavernosum through a nitric oxide-dependent pathway, and sympathetic stimulation in both preventing and terminating erections by contracting the corpus cavernosum. Both these pathways affect activity of CaCCs. The past 5 years produced many successes in CaCC research. One key area of success was the identification of the elusive 'molecular candidate' of CaCCs, as the TMEM16A protein (dubbed anoctamin-1) and potentially other members of the anoctamin family of transmembrane proteins. However, enthusiasm has been somewhat tempered because of evidence that this family of proteins may not be responsible for calcium-activated chloride currents in certain epithelial tissues. Several studies identified specific inhibitors of CaCCs as well as specific inhibitors for anoctamin-1. Despite the number of recent achievements in this field there are many details that still need to be elucidated. Of particular value would be more details on the identity of the CaCCs in corpus cavernosum smooth muscle, using new inhibitors to gain insight into the signalling pathway, and the evaluation of whether inhibition of CaCCs provides any specific benefit in different models of ED.

Premature ejaculation and erectile dysfunction prevalence and attitudes in the Asia-Pacific region.

INTRODUCTION: Premature ejaculation (PE) is a common male sexual dysfunction. The prevalence of PE in the Asia-Pacific region has not been comprehensively studied. AIM: The aim of this study is to evaluate PE prevalence in nine Asia-Pacific countries and the impact of PE on sufferers. METHODS: A random sample of heterosexual males aged 18-65 years in a stable sexual relationship currently or in the past 2 years completed a 48-question survey by computer-assisted interviewing, online, or in-person; the survey and recruitment methodologies varied by location. The survey included demographic questions, the five-question Premature Ejaculation Diagnostic Tool (PEDT), the five-question Sexual Health Inventory for Men (SHIM), and the 10-question Index of Premature Ejaculation (IPE). Separately, men self-reported having PE (lifelong or acquired) or erectile dysfunction (ED). MAIN OUTCOME MEASURES: The PEDT was used to diagnose PE or probable PE; the SHIM was used to diagnose ED; and the IPE was used to assess respondent's attitudes toward PE. RESULTS: Of the 4,997 men who completed the survey, the prevalences of PEDT-diagnosed PE, PEDT-diagnosed probable PE, and self-reported PE were 16%, 15%, and 13%, respectively. Less than half of men with PEDT-diagnosed PE (N = 816) or probable PE (N = 738) self-reported the condition (40% and 19%, respectively), and 6% of men with a PEDT diagnosis of no PE self-reported PE. In contrast, more respondents self-reported ED (8%) than had SHIM-diagnosed moderate or severe ED (5%). IPE responses indicated that 45%, 46%, and 23% of men with PEDT-diagnosed PE were somewhat or very dissatisfied with the length of intercourse before ejaculation, their control over ejaculation, and with sexual intercourse, respectively. CONCLUSIONS: In this study, PE was more prevalent than ED in the Asia-Pacific countries surveyed, but only 40% of men with PEDT-diagnosed PE self-reported PE.

An evidence-based definition of lifelong premature ejaculation: report of the International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation.

OBJECTIVE: To develop a contemporary, evidence-based definition of premature ejaculation (PE). METHODS: There are several definitions of PE; the most commonly quoted, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders - 4th Edition - Text Revision, and other definitions of PE, are all authority-based rather than evidence-based, and have no support from controlled clinical and/or epidemiological studies. Thus in August 2007, the International Society for Sexual Medicine (ISSM) appointed several international experts in PE to an Ad Hoc Committee for the Definition of PE. The committee met in Amsterdam in October 2007 to evaluate the strengths and weaknesses of current definitions of PE, to critically assess the evidence in support of the constructs of ejaculatory latency, ejaculatory control, sexual satisfaction and personal/interpersonal distress, and to propose a new evidence-based definition of PE. RESULTS: The Committee unanimously agreed that the constructs which are necessary to define PE are rapidity of ejaculation, perceived self-efficacy, and control and negative personal consequences from PE. The Committee proposed that lifelong PE be defined as a male sexual dysfunction characterized by ejaculation which always or nearly always occurs before or within about one minute of vaginal penetration, and the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. This definition is limited to men with lifelong PE who engage in vaginal intercourse. The panel concluded that there are insufficient published objective data to propose an evidence-based definition of acquired PE. CONCLUSION: The ISSM definition of lifelong PE represents the first evidence-based definition of PE. This definition will hopefully lead to the development of new tools and patient-reported outcome measures for diagnosing and assessing the efficacy of treatment interventions, and encourage ongoing research into the true prevalence of this disorder, and the efficacy of new pharmacological and psychological treatments.

An evidence-based definition of lifelong premature ejaculation: report of the International Society for Sexual Medicine (ISSM) ad hoc committee for the definition of premature ejaculation.

INTRODUCTION: The medical literature contains several definitions of premature ejaculation (PE). The most commonly quoted definition, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision, and other definitions of PE are all authority based rather than evidence based, and have no support from controlled clinical and/or epidemiological studies. AIM: The aim of this article is to develop a contemporary, evidence-based definition of PE. METHODS: In August 2007, the International Society for Sexual Medicine (ISSM) appointed several international experts in PE to an Ad Hoc Committee for the Definition of Premature Ejaculation. The committee met in Amsterdam in October 2007 to evaluate the strengths and weaknesses of current definitions of PE, to critique the evidence in support of the constructs of ejaculatory latency, ejaculatory control, sexual satisfaction, and personal/interpersonal distress, and to propose a new evidence-based definition of PE. RESULTS: The committee unanimously agreed that the constructs that are necessary to define PE are rapidity of ejaculation, perceived self-efficacy and control, and negative personal consequences from PE. The committee proposed that lifelong PE be defined as ". . . a male sexual dysfunction characterized by ejaculation which always or nearly always occurs prior to or within about one minute of vaginal penetration, and the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy." This definition is limited to men with lifelong PE who engage in vaginal intercourse. The panel concluded that there are insufficient published objective data to propose an evidence-based definition of acquired PE. CONCLUSION: The ISSM definition of lifelong PE represents the first evidence-based definition of PE. This definition will hopefully lead to the development of new tools and Patient Reported Outcome measures for diagnosing and assessing the efficacy of treatment interventions and encourage ongoing research into the true prevalence of this disorder and the efficacy of new pharmacological and psychological treatments.

In vitro and in vivo analysis of co-electrospun scaffolds made of medical grade poly(epsilon-caprolactone) and porcine collagen.

In this study, a nanofiber mesh made by co-electrospinning medical grade poly(epsilon-caprolactone) and collagen (mPCL/Col) was fabricated and studied. Its mechanical properties and characteristics were analyzed and compared to mPCL meshes. mPCL/Col meshes showed a reduction in strength but an increase in ductility when compared to PCL meshes. In vitro assays revealed that mPCL/Col supported the attachment and proliferation of smooth muscle cells on both sides of the mesh. In vivo studies in the corpus cavernosa of rabbits revealed that the mPCL/Col scaffold used in conjunction with autologous smooth muscle cells resulted in better integration with host tissue when compared to cell free scaffolds. On a cellular level preseeded scaffolds showed a minimized foreign body reaction.

Relevance of oestradiol-testosterone balance in erectile dysfunction patients' prognosis.

INTRODUCTION: The ageing process in man is accompanied by a number of endocrine changes including decline in testosterone (T), physiological imbalance between androgen and oestradiol (E2) and changes in the E2-T ratio. In this study, hormone profile data from a group of erectile dysfunction (ED) patients were reviewed to evaluate its impact on ED, with emphasis on oestradiol derangement. METHODS: 30 ED patient case notes with a record of hormone profiles were retrospectively reviewed. Laboratory investigation included levels of total testosterone, total oestradiol, prolactin, luteinising and follicle stimulating hormones, in addition to lipid profile and glucose, based on specific history. These patients were divided into two groups based on the history of presence (Group A) or absence (Group B) of adequate sexual desire. RESULTS: In Group B patients, the E2-T derangement with increasing age was statistically significant with lower serum T level (2.6 ng/ml; range, 1.6-3.7 ng/ml) and elevated E2 level (60 pg/ml; range, 40-120 pg/ml). CONCLUSION: In this preliminary report, although low total testosterone level is seen together with impaired libido and erectile impairment, the accompanying significant increase in E2 indicates the possible role for oestrogen in causation and/or persistence of ED in this group of patients.

Characterization of hypertriglyceridemia-induced erectile dysfunction.

OBJECTIVES: To characterize the effects of experimental hypertriglyceridemia on erectile function. METHODS: The daily water intake of 40 sexually mature male rats (groups II to V) was supplemented for 12 weeks with 10% fructose solution to induce hypertriglyceridemia. In addition, animals from three groups (III, IV, and V) were given through daily oral gavage metformin (group III), fenofibrate (group IV), and fish oil (group V) to estimate their therapeutic effects on fructose-induced metabolic alterations. Another group (I) of 10 rats served as controls. At 12 weeks, changes in sexual behavior and cavernous pressure response to nerve stimulation were correlated with serum triglyceride levels and response to preventive measures. RESULTS: After administration of 10% fructose, triglyceride levels increased fourfold to 1.79 +/- 0.31 mmol/L (mean +/- standard deviation) (group II). Coinciding with this elevation was a significant impairment of the copulatory pattern, with prolongation of mount (3.70 +/- 3.44 minutes), intromission (7.09 +/- 4.49 minutes), and ejaculatory latencies and reduced intracavernous pressure (27.56 +/- 2.04 mm Hg) response to nerve electrical stimulation. Whereas similar significant impairment was seen in group III, the other two groups (IV and V) showed beneficial effects of triglyceride reduction on these parameters. CONCLUSIONS: Our results provide the first evidence for an impact of triglycerides on erectile function. This detrimental effect is likely to be due to functional vascular and neuronal deficits related to hypertriglyceridemia.

Effect of Tribulus terrestris on nicotinamide adenine dinucleotide phosphate-diaphorase activity and androgen receptors in rat brain.

Tribulus terrestris L. (Zygophyllaceae) have been used as an aphrodisiac both in the Indian and Chinese traditional systems of medicine. Administration of Tribulus terrestris extract (TT) increased sexual behaviour and intracavernous pressure both in normal and castrated rats and these effects were probably due to the androgen increasing property of TT. The objective of the present study is to evaluate the effect of TT on nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity and androgen receptor (AR) immunoreactivity in rat brain. Twenty-four adult male Sprague-Dawley rats were divided into two groups of twelve each. Group I was treated with distilled water and Group II was treated with TT at the dose of 5mg/kg body weight orally, once daily for 8 weeks. Following treatment transcardiac perfusion was done with Ringer lactate, 4% paraformaldehyde and 30% sucrose. The brain tissue was removed and sections of the paraventricular (PVN) area of hypothalamus were taken for NADPH-d and AR immunostaining. There was an increase in both NADPH-d (67%) and AR immunoreactivity (58%) in TT treated group and these results were statistically significant compared to the control. Chronic treatment of TT in rats increases the NADPH-d positive neurons and AR immunoreactivity in the PVN region. Androgens are known to increase both AR and NADPH-d positive neurons either directly or by its conversion to oestrogen. The mechanism for the observed increase in AR and NADPH-d positive neurons in the present study is probably due to the androgen increasing property of TT. The findings from the present study add further support to the aphrodisiac claims of TT.

Pregnancy outcomes following pre- and post-implantation exposure of Sprague-Dawley rats to benzyl isothiocyanate.

The present investigation examines the outcomes of rats' pregnancy following pre- and post-implantation maternal exposure (orally) to benzyl isothiocyanate (BITC; 12.5, 25 and 50 mg/kg body weight). Three maternal deaths were recorded in the group of rats treated with 50 mg/kg BITC. Obvious signs of toxicity characterized by hypo-activity, perinasal staining, piloerection, hunched posture and decrease in body weights were observed in BITC-treated rats during the treatment periods. Dose-dependent increase in early fetal resorptions was seen in rats treated with BITC prior to implantation, but was not statistically significant. There were no significant differences in the number of implantation sites in treatment groups compared with the control. Similarly, there were no significant differences in the number of fetal resorptions, relative weights of maternal liver, kidney and spleen of rats in post-implantation treatment groups compared with the control. The differences in the number of viable fetuses in treatment groups compared with the control were also not significant. However, fetal weights in rats treated with 25 and 50 mg/kg BITC and placental weights in all the treatment groups were significantly lower than the control. In conclusion, at 12.5-50 mg/kg, BITC did not cause significant pre- and post-implantation fetal loss in pregnant rats. BITC-induced low fetal and placental weights could be of obstetrical importance, but at levels/doses that would provoke maternal toxicity.

Histaminergic effect of crude papaya latex on isolated guinea pig ileal strips.

In the present study, we investigated the effect of the crude latex of Carica papaya L. (CPX) on isolated guinea pig ileal strips. CPX (0.5-512 microg/ml) caused concentration-dependent contraction of ileal strips suspended in Tyrode solution. The concentration of atropine (0.69 microM) that significantly blocked the contractile effect of acetylcholine on the isolated guinea pig ileum showed no significant effect on CPX- and histamine-induced contractions of the ileal strips. Mepyramine (87.6 nM) significantly blocked the contractile effect of histamine and CPX on the ileum. The same concentration of mepyramine, however, had no significant effect on acetylcholine-induced contraction of the isolated ileal strips. Removal of Ca2+ from the bathing medium abolished ileal contractions induced by acetylcholine, histamine and CPX. All the test substances were able to provoke ileal contractions after replacement of the Ca(2+)-free solution with Tyrode solution. Furthermore, 10(-5) M of nifedipine, a Ca(2+)-entry antagonist, reversibly inhibited the contractile effect of all the test substances on the ileal strips. Results of this study together appear to show that CPX-induced contraction of the isolated guinea pig ileum is mediated via H1-receptors and dependent on extracellular Ca2+ influx.

Estrogen and phytoestrogen predispose to erectile dysfunction: do ER-alpha and ER-beta in the cavernosum play a role?

OBJECTIVES: To investigate the functional changes in rabbit penile corpus cavernosum (CC) secondary to experimental hyperestrogenism and attempt to identify sites of immunoexpression for estrogen receptor subtypes alpha and beta (ER-alpha and ER-beta) in the CC. Although the role of testosterone in sexual function has been extensively studied in clinical settings and experimental animal models, the effect of hormonal modulation/imbalance arising from estrogenic excess has not been characterized. METHODS: Eighteen New Zealand white male rabbits (2.5-3.0 kg) were divided into control and two treatment groups. The two treatment groups were given orally 0.1 mg of estradiol valerate (estradiol group) or phytoestrogen, daidzein (phytoestrogen group) daily for 12 weeks. Blood and tissue samples were collected for hormone levels and in vitro pharmacologic studies. CC samples from untreated rabbits (n = 4) were cryosectioned and incubated with appropriate mouse monoclonal antibody for identification of ER-alpha and ER-beta. RESULTS: Through immunohistochemistry, color signals for nuclear ER-alpha and ER-beta receptors were localized within the CC. Chronic treatment with estradiol and phytoestrogen significantly reduced the systemic total testosterone levels. In organ bath experiments, relaxant responses to acetylcholine, nitroglycerin, and nitrergic transmission were significantly attenuated compared with the control response. With regard to the contractile effect, both types of estrogen treatments significantly potentiated norepinephrine-induced antierectile contraction of the CC. CONCLUSIONS: These results indicate that estradiol treatment and chronic exposure of phytoestrogen may cause receptor-mediated pathophysiologic changes in erectile function, leading to erectile dysfunction.

Oestrogen-androgen crosstalk in the pathophysiology of erectile dysfunction.

Ageing in man is associated with a decline in testosterone following changes in the hypothalamo-pituitary-testicular axis. This may offset the physiologic equilibrium between oestrogen and androgen and at some point when the ratio of free testosterone to oestradiol reaches a critical level, the oestrogenic gonadotropin suppressive effect predominates with decreased release of FSH and LH. Adding to this endocrinal complexity is the continued peripheral conversion to oestradiol through aromatisation. Although the androgen deficiency is not the sole cause for impotence in the elderly, there is a gradual decrease in nocturnal penile tumescence (NPT) and spontaneous morning erections with ageing. Despite the age related increase in oestrogen levels, the information on the pathophysiological role of the "female hormone" in erectile dysfunction has been scanty. Together with our identification of oestrogen receptors within the penile cavernosum, we have delineated dysfunctional changes on male erection mediated by oestradiol. These findings parallel the recent concerns over environmental oestrogens on fertility declines in young men. Oestrogenic activity is also present in plants and thereby in human diet. These phytoestrogens are structurally and functionally similar to oestradiol and more potent than the environmental oestrogenic chemicals such as organochlorine and phenolic compounds. Thus in the light of growing concerns of possible compromising effects on sexuality by endogenous and environmental oestrogens, we are faced with the scientific need to delineate their role on the mechanism of male erectile pathway in health and disease for clinical correlates and prognostics.

Oestrogen-mediated hormonal imbalance precipitates erectile dysfunction.

Declining testosterone (T) in an aging male offsets the equilibrium between androgen and oestrogen (oestradiol, E(2)) with a resultant increase in E(2)-T ratio. Similar functional hormone imbalance is existent in clinical states of hypogonadism and is likely to arise from exposure of males to environmental oestrogens. The pathophysiological significance of this derangement on erectile function, hitherto unknown, was estimated in sexually mature male rats following acute and chronic treatment with oestrogen. A total of 60 male Sprague-Dawley rats (200-250 g) were divided into control and two treatment groups, administered 0.01 and 0.1 mg of oestradiol through oral gavage daily for 1 week (n=30, acute study) and 12 weeks (n=30, long-term study), respectively. Sexual activity in the presence of hormonally primed female rats and intracavernous pressure (ICP) response to electrical stimulation estimated treatment-induced changes, which were correlated with hormone levels and penile morphology at 12 weeks. Following two to five-fold elevation in serum E(2) levels (and simultaneous reduction in testosterone), there was a significant prolongation of mount, intromission, ejaculation latencies and some decrease in frequencies. The ICP response to nerve stimulation was also impaired in all the treated groups. Histologically, trichrome staining highlighted the cavernosal connective tissue hyperplasia in the long-term study groups. Results of this investigation indicate that oestradiol causes pathophysiological changes in erectile function. These observations provide an indirect evidence for the possible sexual health hazards in man upon inadvertent exposure to environmental oestrogens, ageing and derangement of E(2)-T ratio.

The effects of 5HT(1) agonists on erection in rats in vivo and rabbit corpus cavernosum in vitro.

We have examined the effects of the selective 5-HT(1a) and 5-HT(1b) agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) and 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline (CGS12066b), respectively on erection in rats in vivo and rabbit corpus cavernosum in vitro. Apomorphine (0.1 mg/kg) induced 3.1+/-0.4 erections in vehicle-pretreated animals. At the highest doses tested 8-OHDPAT (0.4-0.64 mg/kg) and CGS12066b (1.0-10.0 mg/kg) significantly reduced apomorphine erection to 0.9+/-0.3 erections and 0.5+/-0.2 erections respectively. The nonselective 5-HT agonist metachlorophenylpiperazine (m-CPP; 0.1 mg/kg) elicited characteristic increases in cavernous nerve activity (CNA) and intracavernous pressure responses (ICP) in anesthetized rats. 8-OHDPAT (0.64 mg/kg) and CGS12066b (1.0 mg/kg) failed to elicit CNA or ICP responses. CGS12066b reduced ICP responses resulting from the direct stimulation of the cavernous nerve whereas 8-OHDPAT did not. CGS12066b reduced the CNA and ICP responses to m-CPP administration whereas 8-OHDPAT potentiated m-CPP induced CNA and ICP responses. In isolated rabbit corpus cavernosum (CC) 8-OHDPAT and CGS12066b both failed to alter noradrenergic induced contraction and non-adrenergic non-cholinergic relaxation. Our results indicate that selective 5-HT(1a) and 5-HT(1b) agonists have different effects in different models of erection.

Metachlorophenylpiperazine (m-CPP) induced intracavernous pressure responses in anaesthetized rats.

Here we have recorded the effects of metachlorophenylpiperazine (m-CPP) on intracavernous pressure (ICP) in anesthetized rats pretreated with various pharmacological agents in an attempt to determine the mechanism and relevance of the m-CPP induced ICP response to other models of erection. m-CPP elicited consistent and significantly greater increases in ICP (71.5+/-6.6 mmHg) compared with the mixed 5-HT(2a/2c) agonists trifluoromethylphenylpiperazine (3.4+/-1.3 mmHg) and quipazine (10.9+/-1.8 mmHg). Blockade of 5-HT(2a) receptors with ketanserin failed to unmask any stimulatory effect of quipazine (7.2+/-1.0 mmHg). m-CPP induced ICP responses (71+/-7.0 mmHg) were unaffected in the presence of mianserin (63+/-5 mmHg) and ketanserin (51+/-12 mmHg). Spiperone significantly reduced the m-CPP induced increase in ICP (8.0+/-1.0 mmHg). Naloxone, yohimbine and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) failed to elicit increases in ICP on their own. All three drugs significantly reduced the latency to the first m-CPP induced ICP response compared to saline. Yohimbine increased the duration of m-CPP induced ICP responses whereas 8-OHDPAT increased the mean number of m-CPP induced ICP responses compared to saline. The effects of m-CPP on ICP in anesthetized rats may not be mediated by 5-HT(2c) receptors and appears to be similar to erection in copula, but not erection elicited by other drugs or penile sheath retraction.

Effect of polyphloretin phosphate on the response of non-gravid rat uterus to folkloric and standard oxytocics in vitro.

Polyphloretin phosphate (PPP) has been reported by previous workers to be a specific antagonist of prostaglandin (PGE(1), PGE(2) & PGF(2 alpha))-induced contractions of isolated jird colon, gerbil colon, guinea pig ileum, and rabbit jejunum. In the present study, we examined the effect of PPP on uterotonic activities of crude papaya latex (a folkloric oxytocic), PGF(2 alpha), oxytocin, acetylcholine, and 5-hydroxytryptamine (standard oxytocics) on non-gravid, oestrogen-primed (50 microg/kg) rats in vitro. The effect of PPP on the oxytocics was evaluated qualitatively by incubating the tissues in PPP (25 - 400 microg/ml) for 20 min prior to the addition of a constant concentration of each oxytocic. PPP concentration dependently inhibited the contractile response of the uterine muscles to all the oxytocics. The inhibition was reversible after washing out the drugs. Results of the present study suggest that PPP is a non-specific and reversible antagonist of the response of non-gravid rat uterine smooth muscle to oxytocics in vitro. The specificity of PPP as a prostaglandin antagonist could therefore be species/tissue dependent.

Aphrodisiac properties of Tribulus Terrestris extract (Protodioscin) in normal and castrated rats.

Tribulus terrestris (TT) has long been used in the traditional Chinese and Indian systems of medicine for the treatment of various ailments and is popularly claimed to improve sexual functions in man. Sexual behaviour and intracavernous pressure (ICP) were studied in both normal and castrated rats to further understand the role of TT containing protodioscin (PTN) as an aphrodisiac. Adult Sprague-Dawley rats were divided into five groups of 8 each that included distilled water treated (normal and castrated), testosterone treated (normal and castrated, 10 mg/kg body weight, subcutaneously, bi-weekly) and TT treated (castrated, 5 mg/kg body weight, orally once daily). Decreases in body weight, prostate weight and ICP were observed among the castrated groups of rats compared to the intact group. There was an overall reduction in the sexual behaviour parameters in the castrated groups of rats as reflected by decrease in mount and intromission frequencies (MF and IF) and increase in mount, intromission, ejaculation latencies (ML, IL, EL) as well as post-ejaculatory interval (PEI). Compared to the castrated control, treatment of castrated rats (with either testosterone or TT extract) showed increase in prostate weight and ICP that were statistically significant. There was also a mild to moderate improvement of the sexual behaviour parameters as evidenced by increase in MF and IF; decrease in ML, IL and PEI. These results were statistically significant. It is concluded that TT extract appears to possess aphrodisiac activity probably due to androgen increasing property of TT (observed in our earlier study on primates).

Oxytocics reverse the tocolytic effect of glyceryl trinitrate on the human uterus.

OBJECTIVES: To investigate the effect of glyceryl trinitrate on isolated human pregnant uterine strips and whether the uterine relaxation induced by glyceryl trinitrate could be reversed by oxytocics used in current clinical practice. DESIGN: In vitro pharmacological study. SETTING: Department of Obstetrics & Gynaecology, National University of Singapore, National University Hospital. PARTICIPANTS: Eighteen women who delivered by caesarean section at term. METHODS: Myometrial strips were preloaded with an initial tension of 1.5g in organ baths containing Krebs-Henseleit solution which was aerated with oxygen in 5% carbon dioxide and maintained at 37 degrees C, pH 7.4. The effect of glyceryl trinitrate was studied in strips displaying regular spontaneous contractions. The ability of oxytocin, ergometrine or prostaglandin F2alpha to stimulate uterine contractions was assessed in strips where uterine activity was significantly inhibited by glyceryl trinitrate. RESULTS: Glyceryl trinitrate reduced the amplitude and frequency of spontaneous uterine contractions in a concentration-dependent manner, although the sensitivity of the myometrial strips varied considerably from one specimen to another. The concentration of glyceryl trinitrate producing complete inhibition of myometrial contractions ranged from 44-705 microM. In the presence of glyceryl trinitrate which markedly depressed spontaneous contractions, oxytocin (20 mU/mL), ergometrine (6.15 microM) and prostaglandin F2alpha (6.15 microM) were capable of reversing the uterine activity to either higher than or the untreated level of contractility. CONCLUSIONS: This study demonstrates that glyceryl trinitrate is a potent uterine relaxant in vitro and that the tocolytic effect could be reversed with ease by oxytocics.

Proerectile pharmacological effects of Tribulus terrestris extract on the rabbit corpus cavernosum.

INTRODUCTION: The objective of the present study was to investigate the effect of oral treatment of Tribulus terrestris (TT) extract on the isolated corpus cavernosal tissue of New Zealand white (NZW) rabbits and to determine the mechanism by which protodioscin (PTN), a constituent of the TT, exerts its pharmacological effects. MATERIALS AND METHODS: Twenty-four NZW rabbits were randomly assigned to 4 experimental groups of 6 each. Group I served as control. Groups II to IV were treated with the extract at different dose levels, i.e. 2.5 mg/kg, 5 mg/kg and 10 mg/kg body weight, respectively. The TT extract was administered orally, once daily, for a period of 8 weeks. The rabbits were then sacrificed and their penile tissue isolated to evaluate the responses to both contracting and relaxing pharmacological agents and electrical field stimulation (EFS). RESULTS: PTN on its own had no effect on the isolated corpus cavernosal strips. The relaxant responses to EFS, acetylcholine and nitroglycerin in noradrenaline precontracted tissues from treated groups showed an increase in relaxation of a concentration dependent nature compared to that of the tissues from control group. However, the contractile, anti-erectile response of corpus cavernosal tissue to noradrenaline and histamine showed no significant change between the treatment and the control groups. CONCLUSIONS: The relaxant responses to acetylcholine, nitroglycerin and EFS by more than 10%, 24% and 10% respectively compared to their control values and the lack of such effect on the contractile response to noradrenaline and histamine indicate that PTN has a proerectile activity. The enhanced relaxant effect observed is probably due to increase in the release of nitric oxide from the endothelium and nitrergic nerve endings, which may account for its claims as an aphrodisiac. However, further study is needed to clarify the precise mechanism of its action.