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Biomedical subjects

S Droupy

Publications and source records attributed to S Droupy.

At least 19 recordsLinked to original sources

Melanotan-II: Investigation of the inducer and facilitator effects on penile erection in anaesthetized rat.

The effects of melanotan-II, a non-specific agonist of melanocortin receptors, on erection and its possible sites of action were investigated in anesthetized rats. Delivered i.v. (0.1, 0.3 and 1 mg/kg) or within the paraventricular nucleus of the hypothalamus (0.1 and 1 microg), melanotan-II exerted a dose-dependent inducer activity on erection by eliciting erectile events and shortening latency of the first erectile event to occur. Erectile events were of higher amplitude in rats treated with melanotan-II i.t. (0.2 microg) delivered at the L6-S1 level than in animals treated with the vehicle i.t. delivered. Erectile responses elicited by cavernous nerve stimulation were increased after i.v. melanotan-II (1 mg/kg), thereby exerting facilitator effect on erection. In contrast, melanotan-II injected within the corpus cavernosum (1 microg) did not display any facilitator activity. To investigate the neural pathways involved in the facilitator effect of melanotan-II, we performed acute spinalization (T8 level) and differential selective nerve transections. Neither spinalization nor bilateral transection of pelvic nerves or dorsal penile nerves impaired facilitator activity of i.v. melanotan-II (1 mg/kg). Conversely, the facilitator effect of melanotan-II was abolished after acute removal of the lumbar paravertebral sympathetic chain. These results lead to the conclusion that central and peripheral melanocortin pathways are recruited by melanotan-II, depending on its route of delivery, to exert both inducer and facilitator activities on erection.

Anesthesia↗

The use of telemetry technology to test the proerectile effect of melanotan-II (MT-II) in conscious rats.

OBJECTIVE: The aim of this study is to demonstrate that monitoring, by means of telemetry technology, the increases in intracavernosal pressure (ICP) in freely moving rats using melanotan-II (MT-II) as a proerectile inducer compound is a relevant experimental model to investigate the effects of pharmacological agents on erection. METHODS: Adult rats were implanted in the corpus cavernosum with a pressure sensor which permitted telemetric monitoring of ICP in freely moving animals following MT-II (0.1, 0.3 and 1 mg/kg) or saline i.v. injections. ICP was also measured after MT-II (0.1, 0.3 or 1 mg/kg) or saline i.v. delivery in anesthetized rats. RESULTS: In conscious rats, MT-II (1 mg/kg) significantly increased overall erectile activity compared to saline. In anesthetized rats, MT-II-induced increase in overall erectile activity was not statistically significant but displayed a similar pattern. CONCLUSIONS: The use of telemetry technology allowed to collect quantifiable and reliable data regarding the proerectile activity of MT-II in physiological conditions. The telemetry model appears suitable for investigating the potential inducer proerectile properties of pharmacological agents.

Animals↗

[Prophylaxis of thromboembolic events during urologic surgery].

Few scientific evidences are available in the literature, and the methodologic quality of the studies is often under average. Nevertheless, the conclusions are the following. Nephrectomy, renal transplantation, open surgery of the lower urinary tract and lumbar or pelvic lymph nodes dissection are at high risk for thromboembolic events. Other open or endoscopic urological procedures are at low risk. The laparoscopic approach doesn't change the risk associated with the procedure itself. Thromboprophylaxis is recommended in high-risk procedures. There was no evidence to recommend starting the prophylaxis before more than after the procedure. The use of low molecular weight heparin is recommended for prophylaxis. It can be associated with compressive stockings. It is recommended to treat for around seven days after the procedure. In case of cancer surgery, prophylaxis could be needed for four to six weeks.

Humans↗

[Epidemiology and physiopathology of erectile dysfunction].

Erectile dysfunction (ED) is a common condition with a significant deleterious effect on the quality of life. The prevalence rate of ED is about 20-45% and its incidence in western countries has been evaluated from 25 to 30 cases per 1000 person year. Risk factors of ED are ageing, diabetes, and cardiovascular, uro-genital, psychiatric and any chronic diseases. Smoking, hormonal factors and some drugs may be associated with ED. Modifications of risk factors must be initiated before the age of 50 to prevent ED occurrence. Two thirds of men with ED report embarrassment when discussing this problem with a physician and less than 25% ask for medical advice. As a symptom of endothelial dysfunction, ED may be considered a premonitory sign of coronary or peripheral vascular disease and diabetes.

Diabetes Complications↗

The structure and innervation of the male urethra: histological and immunohistochemical studies with three-dimensional reconstruction.

The structure of the striated urethral sphincter, the so-called rhabdosphincter, remains the subject of controversy. There are two main concepts regarding its structure: either it is a part of the urogenital diaphragm, or it extends from the base of the bladder up to the urogenital diaphragm and is an integral part of the urethra. It is also uncertain whether it possesses a somatic innervation or a mixed innervation (i.e. autonomic and somatic). The purpose of this study was to show the precise location of the nerves running to the urethra, and to try to determine their exact nature. Histology and immunohistochemistry were performed in the external urethral sphincter of ten male fetuses (114-342 mm crown-rump length, or between 14 and 40 weeks of gestation). A three-dimensional (3D) reconstruction of the urethral structure and its innervation was made from serial sections. The 3D reconstruction of the same section levels with different strains allowed us to identify the precise structure of the muscle layers (smooth and striated muscle fibres) and the nature of the nerve elements (myelinated and unmyelinated), their distributions and their relationship to the urethral wall, the prostate and the seminal vesicles. Histological and immunohistochemical 3D reconstruction of the anatomical elements of the urethral sphincter helps us to understand the 3D arrangement of the sphincter muscle layers. It also provides a better understanding of the origin and nature of the nerve elements that play a role in urinary continence.

Gestational Age↗

Surgical treatment of female stress urinary incontinence with a trans-obturator-tape (T.O.T.) Uratape: short term results of a prospective multicentric study.

OBJECTIVE: The aim of the study was to assess the efficacy and safety of a new minimally invasive surgical procedure using the Trans-Obturator-Tape Uratape to treat female stress urinary incontinence. PATIENTS AND METHODS: 183 women with stress urinary incontinence (SUI) associated with urethral hypermobility, underwent the T.O.T. procedure (October 2001 to March 2003). 26 patients were previously operated for incontinence. 26 patients were operated at the same time for their genital prolapse. Mean age was 56 years (29-87). 50/183 patients were having mixed incontinence. A non-elastic, polypropylene tape (UraTape, Mentor-Porgès) with a silicon coated central part was placed under the mid-urethra. The surgical placement technique utilises a trans-obturator percutaneous approach. All patients underwent post-operative clinical examination, cough-stress test (full bladder), uroflowmetry, and post-voiding residual assessment. RESULTS: Mean follow-up was 7 months (1-21). At 1 year follow-up 80.5% of the patients were completely cured and 7.5% were improved. The overall peri-operative complication rate was 2.2% with no vascular, nerve or bowel injury. 6 patients (3.3%) had post-operative urinary retention. CONCLUSION: The present multicentric study confirms the results obtained by the instigator of the technique, E. Delorme, and allows us to consider T.O.T. as an effective and safe technique for the treatment of female stress urinary incontinence, alone or in combination with prolapse repair.

Adult↗

A comparison of the effects of tamsulosin and alfuzosin on neurally evoked increases in bladder neck and seminal vesicle pressure in rats.

OBJECTIVE: To assess the effects of the alpha 1-adrenoceptor antagonists alfuzosin and tamsulosin on the physiological events associated with ejaculation in the rat, because when these drugs are used for treating symptomatic benign prostatic hyperplasia in men they may affect ejaculation by impairing bladder neck closure and seminal vesicle contraction. MATERIALS AND METHODS: In clinical trials the incidence of ejaculatory disorders in men is typically < 1% with alfuzosin and 4-18% with tamsulosin. The effects of tamsulosin and alfuzosin on bladder neck and seminal vesicle pressures (BNP and SVP) in the rat were analysed. Increases in BNP and SVP were induced in urethane-anaesthetized. Wistar rats by electrical stimulation (ES) of the hypogastric nerve (HN) before and after an intravenous injection with vehicle, 3 or 10 micrograms/kg of tamsulosin or alfuzosin (10 rats/group). The mean amplitude and area under the curve (AUC) of the BNP and SVP were expressed as the percentage of the response to ES of HN before the treatment. RESULTS: The amplitude and AUC of the SVP were significantly decreased by both doses of tamsulosin, and marginally decreased by the same doses of alfuzosin. The amplitude of the BNP was significantly decreased by 3 and 10 micrograms/kg of tamsulosin and 10 micrograms/kg alfuzosin, and marginally decreased by 3 micrograms/kg alfuzosin. The AUC of the BNP was significantly decreased by both doses of tamsulosin, but barely affected by alfuzosin at the same doses. CONCLUSION: Over the doses assessed, alfuzosin had significantly less deleterious effect on increases in BNP and SVP induced by ES of the HN than had tamsulosin.

Adrenergic alpha-Antagonists↗

A histopathologic investigation of PGE(2) pathways as predictors of proliferation and invasion in urothelial carcinomas of the bladder.

INTRODUCTION AND OBJECTIVES: The pattern of arachidonate acid (AA) transformation in tumor cells has been shown to play a role in determining tumor cell invasiveness. AA is released from membrane phospholipids by cPLA(2). Then it is metabolized into prostaglandins and PGE(2) especially via cyclooxygenase pathways. PGE(2) production seems to be necessary for rendering the cells invasive. We aimed to characterize cPLA(2), cyclooxygenase 2 (COX2) and prostaglandine E synthase (PGES) expression in human transitional carcinoma (TCC) of the urinary bladder and correlate with the Ki-67 proliferating marker. METHODS: Formalin-fixed human TCC tissues (n=54) obtained from TURB or cystectomies were evaluated for cPLA(2), COX2, PGES and Ki-67 expression using specific antibodies. There were 6 CIS, 9 pTaG1, 9 pTaG3, 10 pT1G3 and 10 pT2G3. 10 normal bladder tissues were also evaluated. Control slides were incubated without primary antibodies and treated in a similar way. RESULTS: cPLA(2), COX2 and PGES were not expressed in the 10 normal tissues. In the same normal tissues, Ki-67 expression was observed only in 1% of the cells. However, cPLA(2) was expressed in 1/6 CIS, 1/9 pTaG1, 3/9 pTaG3, 6/10 pT1G3 and 2/10 pT2G3. COX2 was expressed in 0/6 CIS, 0/10 pTaG1, 2/9 pTaG3, 3/10 pT1G3 and 1/10 pT2G3. PGES was expressed in 4/6 CIS, 0/9 pTaG1, 4/9 pTaG3, 2/10 pT1G3 and 5/10 pT2G3. Ki-67 expression was 39.5% for CIS, 6.5% in pTaG1, 37% in pTaG3, 34.5% in pT1G3 and 55% in pT2G3. If we consider it a positive result when at least one enzyme was expressed, there were 5/6 CIS positive, 1/9 pTaG1 positive, 9/9 pTaG3 positive, 10/10 pT1G3 positive and 10/10 pT2G3 positive. Also the Ki-67 is more often expressed in cells with high grade tumor. CONCLUSIONS: These results suggest that (i). not only COX2 is involved in the tumorogenesis of the TCC but also cPLA(2) and PGES, (ii). there is relationship between the AA metabolic PGE(2) pathway expression and the aggressiveness of the TCC of the urinary bladder.

Aged↗

[Arachidonic acid and prostaglandins, inflammation and oncology].

CYCLOOXYGENASE PATHWAY: Among the 3 metabolic pathways leading to oxidation of arachidonic acid, the cyclooxygenase (COX) pathway produces prostaglandin G2 that is rapidly transformed into prostaglandin H2. PROSTAGLANDINS: Prostaglandins are inflammation mediators that are strongly implicated in tumorgenesis. They participate in tumor initiation, promotion and growth. INFLAMMATION AND EPITHELIAL CANCER: Chronic inflammation is a risk factor for epithelial cancer. It induces prostaglandin synthesis via activation of COX-2. There is a cause and effect relationship between chronic inflammation and carcinogeneis via COX-2 expression. It has been demonstrated that COX-2 favors tumor invasion and inhibits apoptosis. Tumor growth is favored by PGE2-induced reduction in immunity; COX-2 inhibitors reinforce the immune response. Finally COX-2 is expressed in tumor neovessels and plays a role in angiogenesis.

Arachidonic Acid↗

[Cyclooxygenases].

TWO ISOFORMS: There are two isoforms of cyclooxygenase (COX) with similar structure and metabolic activity. COX-1 is a constitutional enzyme. COX-2 is an inductible form. CYCLOOXYGENASE-1: COX-1 is present in most tissues, particularly in the kidney, the digestive tract mucosa, platelets, brain, liver and spleen. CYCLOOXYGENASE-2: COX-2 expression can be induced by an inflammatory process. Implicated in the development of certain cancers, COX-2 is expressed in numerous tumor cell lines and in most epithelial carcinomas. COX-2 favors tumor invasion and inhibits apoptosis. When it is absent, tumor growth is slower or stopped.

Apoptosis↗

[Cyclooxygenase inhibitors].

DISTINCT EFFECTS: Since the discovery of the two isoforms of COX, the therapeutic effects of nonsteroidal antiinflammatory drugs (NSAID) can be distinguished from their adverse effects linked to the inhibition of the constitutional form via selective inhibition of the inducible form. Non-selective NSAID that inhibit both COX isoforms are difficult to use for long-term regimens. NSAID AND CANCER PREVENTION: Epidemiology studies and animal and in vitro studies have demonstrated that regular use of NSAID reduced the incidence of colorectal cancer and certain precancer lesions. PROMISING PERSPECTIVES: COX-2 specific inhibitors, for example cerecoxib or rofecoxib, are potentially interesting for human therapy for chemoprevention of epithelial cancer or as medical treatment, alone or in combination with other anticancer treatments.

Animals↗

[Gas embolism during radical nephrectomy by retroperitoneal laparoscopy].

A case of CO2 gas embolism occurring during retroperitoneal laparoscopic right radical nephrectomy in a 70-year-old-woman is reported. Patient's outcome was excellent after venous clamping, fluid loading and application of a positive and expiratory pressure. Gas embolism is a well documented complication of laparoscopic surgery, but has been rarely described in retroperitoneal laparoscopy for urologic procedure. The retroperitoneal surgical site, the major surgical procedure with vessel manipulation and the left lateral position seem to be the risk factors for gas embolism in this case.

Aged↗