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S Minhas

Publications and source records attributed to S Minhas.

26 records · Page 2Linked to original sources

Endothelial and neuronal-derived nitric oxide mediated relaxation of corpus cavernosal smooth muscle in a rat, in vitro, model of erectile function.

We set out to establish a simple, reproducible, rat in vitro model of erectile function and to use this to demonstrate the functional importance of both neuronal- and endothelial-derived nitric oxide within this animal. Two corpora cavernosal smooth muscle strips were harvested from sexually mature male Wistar rats and mounted in an organ bath for measurement of isometric tension. Following contraction with noradrenaline the strips were relaxed by the addition of either acetylcholine or sodium nitroprusside. Electrical field stimulation was performed in the presence of atropine and guanethidine. Relaxation responses were repeated in the presence of methylene blue, L-arginine, L-NNA and haemoglobin +/- L-arginine. Methylene blue abolishes the relaxation to acetylcholine and EFS; L-NNA and haemoglobin cause a significant impairment in the relaxation response. L-arginine reverses the effect of haemoglobin. In conclusion, the inhibitory, relaxant stimulus of rat corpora cavernosa is due to both neuronal nitric oxide and endothelial-derived nitric oxide released in response to cholinergic stimulation.

Animals↗

The role of prostaglandins in penile erection.

The balance of penile smooth muscle tone is finely controlled, with contractile factors acting in opposition to relaxant factors. The principal agents in this process are undoubtedly noradrenaline and nitric oxide. Prostaglandins probably have a crucial role in the 'fine tuning' of corporal smooth muscle tone. Their effects on control mechanisms in the healthy penis are more likely to be modulatory rather than direct.

Endothelium↗

The effect of cyclic GMP on rabbit corporal smooth muscle tone and its modulation by cyclo-oxygenase products.

Corporal smooth muscle (CSM) tone is maintained by a finite balance between relaxant and contractile neurotransmitters. The aim of these experiments was to ascertain the degree to which cyclic GMP is involved in these interactions. We also sought to elucidate the pharmacological mechanism of action of MB in rabbit corpus cavernosum (RCC), an important tool in nitric oxide research. Using an organ chamber technique, strips of RCC were treated with the guanylate cyclase inhibitors Methylene Blue (MB) and LY83583; 100 microM MB led to increases in resting tension which were antagonized by indomethacin, nifedipine, phentolamine, but not superoxide dismutase (SOD). Contractile responses to noradrenaline (NA) were increased and relaxation to ACh was impaired by both MB and LY83583 and reversed with indomethacin, but not SOD. Pyrogallol had no effect on agonist-induced responses. The pharmacological action of MB in RCC does not depend on the generation of superoxide anions. Endothelium-dependent relaxation in RCC results in activation of soluble guanylate cyclase and release of a stable endothelium derived contracting factor(s), which is likely to be a constrictor prostanoid(s). Tonic production of cGMP in RCC inhibits the presynaptic release and contractile effects of NA and can be modulated by cyclo-oxygenase inhibition, demonstrating the important interaction and functional antagonism between cGMP and prostaglandins in the control of CSM tone.

Acetylcholine↗

Extra-anatomic stents in ureteric obstruction: experience and complications.

OBJECTIVE: To assess the role of extra-anatomic stents (EAS) as a means of urinary diversion in patients with ureteric obstruction secondary to malignancy. PATIENTS AND METHODS: The technique for inserting EAS in patients with ureteric obstruction was described previously; to date, 13 patients (seven women and six men, mean age 45.3 years, range 22-78) have been treated. All patients had ultrasonographic evidence of hydronephrosis and/or significant biochemical evidence of renal impairment. Patients had advanced malignancy and one patient an abdominal aortic aneurysm. RESULTS: Urinary diversion was successful in all patients; two survived for more than 1 year, with stent changes at 6-monthly intervals. In three patients the stents were replaced by percutaneous nephrostomies because of problems with leakage or infection. The remaining patients died with functioning EAS in situ. CONCLUSIONS: In patients with ureteric obstruction secondary to malignancy or medical conditions excluding them from more invasive surgery, EAS provide a further therapeutic option instead of a permanent nephrostomy, which has associated inherent problems. This technique is not without potential problems and careful selection of patients remains vital in this difficult area.

Adult↗

The evaluation of sexual function in men presenting with symptomatic benign prostatic hyperplasia.

OBJECTIVE: To evaluate quantitatively and qualitatively the degree of sexual dysfunction in an unselected population of men attending a prostate-assessment clinic using a sexual-function inventory, and to ascertain the degree of correlation between sexual dysfunction, urinary symptoms and age. PATIENTS AND METHODS: In all, 168 men with symptomatic BPH attending a prostate assessment clinic were investigated prospectively using the International Prostate Symptom Score (IPSS), BPH Impact Index (BPHII), a measurement of urinary flow rate and residual urine volume, and a sexual function questionnaire. The results were assessed using Spearman's rank order correlation to discern any correlations between the measured variables. RESULTS: The data from 140 patients were available for analysis; of these, low scores were obtained in 59% for sexual drive, in 56% for erections (with 46% of men satisfying the National Institute of Health criterion for impotence) and in 38% for ejaculation. There was a statistically significant rank order correlation between age and the sexual symptom scores for each of the three categories (sexual drive, erection and ejaculation), but no correlation between age and the problem assessment scores for these domains, suggesting that the older patients are just as bothered by their sexual dysfunction as the younger men. Furthermore, the BPHII scores correlated weakly but significantly with all aspects of sexual function, including overall sexual satisfaction, in contrast to the poor correlation seen with the total IPSS and sexual function scores. CONCLUSION: There is a significant number of patients with symptomatic BPH who have sexual dysfunction, with the proportion increasing with advancing age and with the older men still showing a high degree of bother from their symptoms. Sexual function scores were better correlated with BPHII scores than with the total IPSS, although some of the individual IPSS questions correlated well.

Adult↗

Novel PDE5 inhibitors for the treatment of male erectile dysfunction.

Erectile dysfunction (ED) affects the lives of approximately 150 million men worldwide. ED may be a cause of male sub-fertility in a significant proportion of patients. There is now an expanding armamentarium for the management of ED, including oral agents such as phosphodiesterase type 5 (PDE5) inhibitors. PDE5 inhibitors may also be useful in situations of temporary ED in couples undergoing IVF. Two novel PDE5 inhibitors have been commercially launched in the European Union in the first quarter of 2003. This article reviews the pharmacology and clinical efficacy of these new agents and their potential role in treating patients with male sub-fertility.

3',5'-Cyclic-GMP Phosphodiesterases↗

Investigation of cavernosal smooth muscle dysfunction in low flow priapism using an in vitro model.

The effects of hypoxia (pO2: 50 mmHg), acidosis (pH: 6.9) or glucopenia (absence of glucose) in vitro on the tone of the rabbit corpus cavernosum were investigated. The recovery of smooth muscle contractility following exposure to these conditions was also assessed. Hypoxia, acidosis or glucopenia alone or in combination showed a sustained reduction in the tone. Reperfusion of tissue strips showed complete recovery of smooth muscle tone for all conditions except when hypoxia and glucopenia were combined or when hypoxia, glucopenia and acidosis were used in combination. Incomplete recovery of tone was associated with a significant reduction in tissue ATP concentrations and an increase in the number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling)-positive nuclei. This indicates that following reversal of hypoxia, acidosis and glucopenia, failure of conventional alpha-adrenergic agonists to produce tumescence in low flow priapism is associated with irreversible smooth muscle cell dysfunction, which is linked to ATP reduction and smooth muscle cell death.

Acidosis↗