Search PubMed⌕ Search

Biomedical subjects

P Clément

Publications and source records attributed to P Clément.

At least 19 recordsLinked to original sources

Effect of acute dapoxetine administration on the pudendal motoneuron reflex in anesthetized rats: comparison with paroxetine.

PURPOSE: Pudendal motoneuron reflex discharges elicited by bilateral electrical stimulation of the dorsal nerves of the penis were used as an experimental model of the expulsion reflex of ejaculation to investigate the effect of acute intravenous delivery of dapoxetine, a short acting selective serotonin reuptake inhibitor, in anesthetized rats. Dapoxetine was compared with paroxetine, the selective serotonin reuptake inhibitor of reference. MATERIALS AND METHODS: Stimulating electrodes were placed bilaterally on the dorsal nerves of the penis and a recording electrode was placed on the motor branch of the pudendal nerve to monitor pudendal motoneuron reflex discharges in urethane anesthetized rats. Pudendal motoneuron reflex discharges induced by penile dorsal nerve stimulation were measured before and 60 minutes after a single intravenous injection of dapoxetine or paroxetine, each tested at 3 doses (1, 3 and 10 mg/kg) or after a single injection of vehicle. RESULTS: At all doses tested dapoxetine significantly lengthened the latency of pudendal motoneuron reflex discharges following bilateral stimulation of the dorsal nerves of the penis in comparison with vehicle, whereas only the 1 mg/kg dose of paroxetine was effective. The amplitudes of pudendal motoneuron reflex discharges were significantly decreased only in rats treated with 3 mg/kg dapoxetine compared to vehicle. CONCLUSIONS: Acute systemic delivery of selective serotonin reuptake inhibitors is capable of modulating the expulsion reflex of ejaculation in anesthetized rats with dapoxetine appearing to be more effective than paroxetine. These findings support the beneficial effect of on-demand administration of dapoxetine for premature ejaculation.

Anesthesia↗

Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00).

BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of fulvestrant, an estrogen receptor antagonist, in postmenopausal women with hormone-responsive tumors progressing after aromatase inhibitor (AI) treatment. PATIENTS AND METHODS: This is a phase II, open, multicenter, noncomparative study. Two patient groups were prospectively considered: group A (n=70) with AI-responsive disease and group B (n=20) with AI-resistant disease. Fulvestrant 250 mg was administered as intramuscular injection every 28 (+/-3) days. RESULTS: All patients were pretreated with AI and 84% also with tamoxifen or toremifene; 67% had bone metastases and 45% liver metastases. Fulvestrant administration was well tolerated and yielded a clinical benefit (CB; defined as objective response or stable disease [SD] for >or=24 weeks) in 28% (90% confidence interval [CI] 19% to 39%) of patients in group A and 37% (90% CI 19% to 58%) of patients in group B. Median time to progression (TTP) was 3.6 (95% CI 3.0 to 4.8) months in group A and 3.4 (95% CI 2.5 to 6.7) months in group B. CONCLUSIONS: Overall, 30% of patients who had progressed following prior AI treatment gained CB with fulvestrant, thereby delaying indication to start chemotherapy. Prior response to an AI did not appear to be predictive for benefit with fulvestrant.

Adult↗

[Positron emission tomography in head and neck squamous cell carcinomas].

18F-Fluorodeoxyglucose positron emission tomography (PET) is an imaging modality which is becoming increasingly esential in oncology, especially in the management of head and neck squamous cell carcinomas (SCC). The most common uses of the PET are listed in this thematic study: initial staging, cervical lymph node metastases from an unknown primary tumor and post-therapeutic follow-up. The advantages and drawbacks of this imaging tool are exposed here according to both our experience and data from the literature. Decision schemes are suggested for each use so as to optimize the use of this imaging modality in the management of these SCC. Other fields of application for the PET are mentioned, such as the in-progress evaluation of response to chemotherapy, the interest of this imaging tool in radiotherapy as well as current biochemical developments concerning new tracers.

Carcinoma, Squamous Cell↗

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↗

Potential role of inducible nitric oxide synthase in the sleep-wake states occurrence in old rats.

Extensive evidences now suggest that an association between inducible nitric oxide synthase and oxidative stress takes place during aging. Since the part played by inducible nitric oxide synthase in the sleep impairments associated with aging still remains unexplored, we compared its involvement in old rats (20-24 months) versus adult ones (3-5 months) using polygraphic, biochemical, voltammetric and immunohistochemical techniques. The experiments were conducted either in basal condition or after a systemic injection of selected inducible nitric oxide synthase inhibitors. We found that 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (10 mg/kg, i.p.) or aminoguanidine (400 mg/kg, i.p.) was capable to suppress rapid-eye-movement sleep and induce a delayed enhancement in slow-wave sleep in old rats. These effects did not occur in adult animals. Within the frontal cortex, the laterodorsal tegmentum and dorsal raphe nuclei, the basal inducible nitric oxide synthase activity was 85-200% higher in old rats than in adult ones. In contrast, the neuronal nitric oxide synthase activity did not vary in both groups. 2-Amino-5,6-dihydro-6-methyl-4H-1,3-thiazine administration significantly reduced inducible nitric oxide synthase activity (70-80% according to the brain areas) independently of age, but significantly decreased the cortical nitric oxide release in old rats. Finally, in frontal cortex and dorsal raphe immunohistochemical analysis showed inducible nitric oxide synthase-positive cells again only in old animals. These data support the idea that nitric oxide produced by inducible nitric oxide synthase plays a role in the triggering and maintenance of rapid-eye-movement sleep during aging.

Age Factors↗

Recombinant human LH supplementation during GnRH antagonist administration in IVF/ICSI cycles: a prospective randomized study.

BACKGROUND: When administered in the late follicular phase to prevent an LH surge, GnRH antagonists induce a sharp decrease in serum LH levels that may be detrimental for assisted reproductive technology cycle outcome. Therefore, a prospective study was designed to assess the effects of recombinant human (r)LH supplementation during GnRH antagonist (cetrorelix) administration. METHODS: The protocol consisted of cycle programming with oral contraceptive pill, ovarian stimulation with rFSH and flexible administration of a single dose of cetrorelix (3 mg). A total of 218 patients from three IVF centres were randomized (by sealed envelopes or according to woman's birth date) to receive (n = 114) or not (n = 104) a daily injection of rLH 75 IU from GnRH antagonist initiation to hCG injection. RESULTS: The only significant difference was a higher serum peak E2 level in patients treated with rLH (1476 +/- 787 versus 1012 +/- 659 pg/ml, P < 0.001) whereas the numbers of oocytes and embryos as well as the delivery rate (25.2 versus 24%) and the implantation rate per embryo (19.1 versus 17.4%) were similar in both groups. CONCLUSIONS: These results show that in an unselected group of patients, there is no evident benefit to supplement GnRH antagonist-treated cycles with rLH.

Adult↗

Changes in the sleep-wake cycle architecture and cortical nitric oxide release during ageing in the rat.

Changes in sleep-wake states and nitric oxide release were examined in aged rats versus young-adult ones. Sleep-wake recordings and nitric oxide measurements were taken from animals chronically equipped with polygraphic and voltametric electrodes. Animals were examined in baseline conditions and in response to a 24-hour paradoxical sleep deprivation. In aged rats, basal amount of paradoxical sleep is decreased during the light phase versus young-adult animals. After paradoxical sleep deprivation, a paradoxical sleep rebound occurs with an amount and intensity that are less marked in aged animals than in young-adult rats. The amplitude of the circadian distribution for wakefulness, slow-wave sleep and paradoxical sleep amounts is reduced with age. Finally, delta-slow-wave sleep and theta-paradoxical sleep power spectra are attenuated either in baseline conditions or after paradoxical sleep deprivation in aged animals. It is also reported that cortical nitric oxide release exhibits a circadian rhythm with higher amplitude in aged rats than in young-adult ones. However, after paradoxical sleep deprivation, a limited overproduction of nitric oxide is obtained compared with young-adult ones. These results, evidencing the dynamics of the nitric oxide changes occurring in relation to the sleep-wake cycle, point out the homeostatic paradoxical sleep regulation as an age-dependent process in which the nitric oxide molecule is possibly involved.

Aging↗

In vitro release of caffeine from concentrated W/O emulsions: effect of formulation parameters.

Concentrated water in oil emulsions have been obtained with four different emulsifiers to study the effect of formulation parameters on the in vitro release of caffeine. The in vitro release was studied on polysulfone membranes. Among the four emulsifiers, only one gave a statistically higher release of caffeine after 15 h (at a fixed percentage of dispersed phase). The concentration of the emulsifier does not have a significant effect on the release of caffeine. In contrast, diffusion of caffeine from concentrated W/O emulsions has been found to be highly dependent on the internal phase volume. The flux of caffeine increases with the percentage internal water phase. The droplet diameter decreases and the apparent viscosity increases with the percentage of the dispersed phase. And, the shape of the droplets goes from spherical to polyhedral as the percentage dispersed phase is increased. However, the flux could be correlated neither with the apparent viscosity nor with the droplet diameter at a fixed percentage of the dispersed phase. Results suggest that the shape factor may have an influence on the release of caffeine from concentrated emulsions. All the release profiles followed a zero-order kinetic.

Caffeine↗

Effects of constant or variable thermal rearing condition: a behavioural approach using an automated tracking system in Blaberus craniifer.

An automatic tracking device was used to investigate exploratory behaviour of the cockroach, Blaberus craniifer, with regard to the influence of rearing temperature. Two groups were tested, one under variable rearing temperature, the other under constant rearing temperature. Rearing temperature influenced both the rate of decrease of linear speed and the spatial occupation of an open arena. Linear speed decreased with time and was higher during the first 10 minutes of recording for the animals reared under constant temperature conditions. The decrease fitted a linear model for the variable temperature group, whereas it was steeper than exponential for the constant temperature group. Frequency of occupancy in the peripheral zone of the arena was not affected by time and was always higher for the animals of the constant condition group. The results are interpreted as a function of the different thermal rearing conditions.

Journal Article↗

Influence of three synthetic membranes on the release of caffeine from concentrated W/O emulsions.

We measured the release rate characteristics of caffeine from concentrated emulsions using three different sources of synthetic membranes. The formulations tested included, on the one hand, two stable cosmetic concentrated W/O emulsions (90% w/w) - one with a non ionic surfactant and one with a silicone surfactant - and on the other hand, a commercially available hydroalcoholic gel. All formulations contained 5% caffeine. In vitro diffusion measurements (24 h) were performed with static diffusion Franz cells. A silicone membrane could not allow us to differentiate the two concentrated emulsions (CE), but the two other membranes, not rate limiting, showed difference in the release profile of caffeine from the two CE. Results with the cellulose and polysulfone membrane showed that in vitro release of caffeine is influenced by the nature of the emulsifier in the concentrated emulsion, the non ionic surfactant being more efficient than the silicone surfactant. The polysulfone membrane was the only one that allows statistical differentiation of the three products. For further studies the polysulfone membrane will be use to make screening on concentrated emulsions.

Caffeine↗

Deletions of mob and tra pJP4 transfer functions after mating of Ralstonia eutropha JMP134 (pJP4) with Escherichia coli harboring F'::Tn10.

One-tenth of Escherichia coli transconjugants resulting from the transfer of the catabolic plasmid pJP4 from Ralstonia eutropha JMP134 to E. coli XL1Blue, contained pJP4 derivatives with deletions (approximately 15-30 kb). The occurrence of these deletions is probably associated with the presence of Tn10 in the recipient. DNA endonuclease restriction analysis of the pJP4 deletion derivatives showed the absence of SphI and EcoRI fragments previously reported to hybridize with IncP Tra DNA probes. Moreover, these pJP4 deletion derivatives are not able to self-transfer, nor are they able to be mobilized. Accordingly, these pJP4 deletion derivatives lack transfer functions.

Bacterial Proteins↗

Degradation of trichlorophenols by Alcaligenes eutrophus JMP134.

The degradation of chlorophenols by Alcaligenes eutrophus JMP134 (pJP4) was studied. The strain grew on 2,4,6-trichlorophenol or 2,4,6-tribromophenol as the sole carbon and energy source. Complete degradation of 2,4,6-trichlorophenol was confirmed by chloride release and gas chromatography analysis of supernatants from growth cultures. The 2,3,5-, 2,3,4-, 2,3,6- and 2,4,5-isomers of trichlorophenol did not support growth. However, up to 40% of 2,4,5-trichlorophenol was mineralized during growth of A. eutrophus on chemostats fed with either phenol (0.4 mM) or 2,4,6-trichlorophenol (0.4 mM) plus 2,4,5-trichlorophenol (0.1 mM). Growth on 2,4,6-trihalophenols was also observed in A. eutrophus JMP222, the strain lacking pJP4, suggesting that this new degradative ability reported for A. eutrophus is not related to pJP4 encoded catabolic functions.

Alcaligenes↗

[Resorption of the lavage fluid during transurethral resection of the prostate. Apropos of 13 cases].

The authors report on thirteen patients who developed a variety of symptoms after transurethral resection of the prostate; confusion, seizures, blurred vision with mydriasis, nausea and vomiting, bradycardia, and hypotension. This post-resection syndrome is caused by resorption of a large amount of the hypotonic solution used during the surgical procedure and containing 1.5% glycine. Postoperative sodium levels were assayed in all patients and consistently found to be low (105 to 124 mEq/l). Serum glycine was measured in three patients and the very high levels found suggest that absorption of glycine during transurethral resection of the prostate may contribute to the symptoms of encephalopathy.

Absorption↗

[Thoracic epidural anesthesia for extracorporeal lithotripsy. Comparison of 4 anesthetic solutions].

Extracorporeal shock-wave lithotripsy (ESWL) is a new non-invasive procedure allowing disintegration of upper urinary tract calculi, usually carried out in epidural anaesthesia (EA). The patient strapped to a stretcher is immersed in a bath. At the bottom of the tube is the shock-wave generator. The release of shock waves (1,000 to 2,000 for each treatment) is triggered by the R-wave of the patient's ECG. Arrhythmias and extrasystoles (ES) may occur. In the investigational trial, the preferred anaesthesia was continuous lumbar EA with a large volume of 2% lidocaine extended to the level of T6. This study was conducted to assess continuous thoracic EA at the T12 interspace with a lesser dose (12 ml) of 2% lidocaine (XT, comparing it with single dose EA with the same volume of three other agents: bupivacaine 0.5% (Ma) and mixtures of 2% lidocaine-0.2+ tetracaine (XT), and 2% lidocaine-fentanyl 50 micrograms (XF), all with 1/200,000th adrenaline. Eighty patients (ASA class I or II) were assigned randomly to receive one of the four types of EA. All were monitored with Holter's method. The demographic distribution was similar for the four groups. Mean duration of the procedure was 32 +/- 15 min. Premedication was given only in 16 patients, very anxious. The results were excellent in 68 patients; 11 had to be supplemented with one or two doses of intravenous agents: diazepam and/or fentanyl: one failure was given an intravenous general anaesthesia. Mild hypotension occurred in four patients. 242 ES occurred in 48 patients (60%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗