PubMed Health⌕ Search

Biomedical subjects

C Smadja

Publications and source records attributed to C Smadja.

At least 19 recordsLinked to original sources
PubMed2006

Chromatographic behaviour of peptides on a mixed-mode stationary phase with an embedded charged group by capillary electrochromatography and high-performance liquid chromatography.

Retention behaviour of biological peptides was investigated on a stationary phase bearing an embedded quaternary ammonium group in a C21 alkyl chain by both high-performance liquid chromatography (HPLC) and capillary electrochromatography (CEC). In HPLC experiments, variation of acetonitrile (ACN) content in the mobile phase showed that peptides are mainly separated by RP mechanism. The weak or negative retention factors observed as compared to C18 silica stationary phase suggested the involvement of an electrostatic repulsion phenomenon in acidic conditions. Comparison of HPLC and CEC studies indicated that (i) ion-exclusion phenomenon is more pronounced in HPLC and (ii) higher ACN percentage in mobile phase induce for some peptides an increase of retention in CEC, pointing out the existence of mechanisms of retention other than partitioning mainly involved in chromatographic process. This comparative study demonstrated the critical role of electric field on peptide retention in CEC and supports the solvatation model of hydrolytic pillow proposed by Szumski and Buszewski for CEC using mixed mode stationary phase in CEC.

Angiotensinogen↗
PubMed2005

Asymmetrical reproductive character displacement in the house mouse.

Our study addressed reproductive character displacement between two subspecies of the house mouse, Mus musculus musculus and Mus musculus domesticus that hybridize in Europe along a zone where selection against hybridization is known to occur. Based on a multi-population approach, we investigated spatial patterns of divergence of mate preference in the two taxa. Mate preference was significantly higher in the contact zone than in allopatry in both subspecies, suggesting that reproductive character displacement occurs. Moreover, patterns of preference were stronger in M. m. musculus than in M. m. domesticus, indicating an asymmetrical divergence between the two. In the context of selection against hybridization, our results may provide empirical support for the hypothesis of reinforcement in a parapatric hybrid zone. We discuss factors that could explain the asymmetrical pattern of divergence and the possible impact of a unimodal structure on the maintenance of premating divergence between the two subspecies.

Analysis of Variance↗
PubMed2004

Reproductive character displacement is not the only possible outcome of reinforcement.

We study the form of the clines in a female mating preference and male display trait using simulations of a hybrid zone. Allopatric populations of two species are connected by demes in a stepping stone arrangement. Results show that reproductive character displacement (a pattern of increased prezygotic isolation in sympatry compared with allopatry) may or may not result when there is reinforcement (defined here as the strengthening of prezygotic isolation as a result of selection against hybrids, relative to the amount of prezygotic isolation present when hybrids are not selected against). Further, reproductive character displacement of the preference may or may not occur when it occurs in the male display. We conclude that the absence of reproductive character displacement is not evidence against the operation of reinforcement.

Animals↗
PubMed2001

Mice with very low expression of the vesicular monoamine transporter 2 gene survive into adulthood: potential mouse model for parkinsonism.

We have created a transgenic mouse with a hypomorphic allele of the vesicular monoamine transporter 2 (Vmat2) gene by gene targeting. These mice (KA1) have profound changes in monoamine metabolism and function and survive into adulthood. Specifically, these animals express very low levels of VMAT2, an endogenous protein which sequesters monoamines intracellularly into vesicles, a process that, in addition to being important in normal transmission, may also act to keep intracellular levels of the monoamine neurotransmitters below potentially toxic thresholds. Homozygous mice show large reductions in brain tissue monoamines, motor impairments, enhanced sensitivity to dopamine agonism, and changes in the chemical neuroanatomy of the striatum that are consistent with alterations in the balance of the striatonigral (direct) and striatopallidal (indirect) pathways. The VMAT2-deficient KA1 mice are also more vulnerable to the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in terms of nigral dopamine cell death. We suggest that the mice may be of value in examining, long term, the insidious damaging consequences of abnormal intracellular handling of monoamines. On the basis of our current findings, the mice are likely to prove of immediate interest to aspects of the symptomatology of parkinsonism. They may also, however, be of use in probing other aspects of monoaminergic function and dysfunction in the brain, the latter making important contributions to the pathogenesis of schizophrenia and addiction.

Animals↗
PubMed2001

[Comparative incidence of protrusive atheromatous plaques of the thoracic artery in patients with atrial fluter and atrial fibrillation].

Although it has been demonstrated recently that in patients with atrial fibrillation, protrusive atheromatous plaques of the thoracic aorta (thickness 4 mm) and left atrial abnormalities such as thrombosis, spontaneous contrast and low atrial blood flow velocities carry an additional embolic risk, this has not yet been studied in atrial flutter. Out of 2493 patients undergoing transoesophageal echocardiography between September 1993 and December 1997, 271 consecutive patients in atrial flutter (N = 41) or fibrillation (N = 230) for over 48 hours, underwent transoesophageal echocardiography before cardioversion. Patients with atrial flutter were compared with those with atrial fibrillation. Their characteristics were comparable with respect to age (68 +/- 13 and 67 +/- 12 years respectively, p = 0.628), sex ratio (men 66 and 54% respectively, p = 0.212), previous thromboembolic disease (5 and 15% respectively, p = 0.126). The incidence of protrusive aortic atheroma (12 and 11% respectively, p = 0.919), of spontaneous contrast in the thoracic aorta (15 and 14% respectively, p = 0.847) were identical in both groups. The left atrium was significantly smaller (3.1 +/- 0.7 and 6 +/- 3 cm2 respectively, p = 0.001), spontaneous atrial contrast less frequent (17 and 37% respectively, p = 0.024) and the velocities of atrial emptying higher (47 +/- 10 and 30 +/- 10 cm/s respectively, p = 0.030) in patients with flutter compared with atrial fibrillation. There was no difference in left ventricular fractional shortening (30 +/- 10 and 33 +/- 13% respectively, p = 0.630), the presence of rheumatic valvular disease (5 and 12%, p = 0.301), left atrial diameter (43 +/- 7 and 45 +/- 8, p = 0.134), right atrial surface area (16 +/- 4 and 17 +/- 6 cm2, p = 0.384) or in intraatrial thrombosis (2 and 3%, p = 0.888) respectively. These results show a high prevalence of protrusive atheroma of the thoracic aorta both in atrial flutter and in atrial fibrillation, and fewer left atrial abnormalities in patients with flutter.

Aged↗
PubMed2000

Prevention of recurrent depressive episodes with milnacipran: consequences on quality of life.

BACKGROUND: Depression is now seen as a chronic disabling condition that spans the patient's lifetime and creates significant medical, economic and quality of life consequences. METHODS: 500 depressed patients were treated with milnacipran for 6 months. A total of 214 recovered patients were randomised to receive either milnacipran (50 mg bid) or a matching placebo for a 1-year recurrence prevention phase. Recurrence rate was the primary criteria; quality of life (QoL) consequences were evaluated through a shortened version of the French Sickness Impact Profile (SIP), the Depression Impact Profile (DIP). RESULTS: Milnacipran demonstrated its ability to reduce recurrences (Odds-Ratio=1.5; P<0.05), with a more marked effect in recovered patients with few residual symptoms (Odds-Ratio=3.0). Responders who continued treatment with milnacipran had a dramatic improvement in their quality of life, although patients with residual symptoms still experienced some deterioration in their QoL (recreation, emotional, social, alertness and home assistance scores). Even recovered patients having zero scores on the Hamilton Depression Rating Scale-21 items (HDRS) had some QoL deterioration. The DIP emotional score was found to be more predictive of recurrence than the HDRS. Overall, the QoL was improved for those in the milnacipran group in comparison to placebo on the mobility, communication, psycho-social and total scores. LIMITATIONS: The QoL evaluation was a secondary criteria; no a priori sample size estimate was performed. The choice of a generic QoL instrument might have reduced the sensitivity to clinical changes in depression. CONCLUSIONS: Prevention of recurrence in MDD with milnacipran contributes to an improvement in the QoL.

Adolescent↗
PubMed1999

Altered emotional and locomotor responses in mice deficient in the transcription factor CREM.

Various transcription factors act as nuclear effectors of the cAMP-dependent signaling pathway. These are the products of three genes in the mouse, CREB, CRE modulator (CREM), and ATF-1. CREM proteins are thought to play important roles within the hypothalamic-pituitary axis and in the control of rhythmic functions in the pineal gland. We have generated CREM-mutant mice and investigated their response in a variety of behavioral tests. CREM-null mice show a drastic increase in locomotion. In contrast to normal mice, the CREM-deficient mice show equal locomotor activity during the circadian cycle. The anatomy of the hypothalamic suprachiasmatic nuclei, the center of the endogenous pacemaker, is normal in mutant mice. Remarkably, CREM mutant mice also elicit a different emotional state, revealed by a lower anxiety in two different behavioral models, but they preserve the conditioned reactiveness to stress. These results demonstrate the high degree of functional specificity of each cAMP-responsive transcription factor in behavioral control.

Animals↗
PubMed1999

Elective laparoscopic sigmoid colectomy for diverticulitis. Results of a prospective study.

BACKGROUND: We undertook a prospective evaluation of elective laparoscopic sigmoid colectomy for diverticulitis in order to assess the risks and benefits of this approach. METHODS: Between November 1992 and November 1996, 54 consecutive patients were included in this study. Their mean age was 59 +/- 13 years (range, 36-81). The number of attacks of diverticulitis before colectomy ranged from one to four (mean, 2.2 +/- 0.7). The operative technique consisted of elective division of the inferior mesenteric vessels, left colonic flexure mobilization, and colorectal anastomosis using the cross-stapling technique. RESULTS: Five procedures (9.2%) were converted. The primary cause for conversion was obesity. These patients had a simple postoperative course. There were no postoperative deaths. Three patients (6.1%) developed abdominal complications, and four patients (8.2%) had abdominal wall complications. Postoperative paralytic ileus lasted only 2.3 +/- 0.7 days (range, 1-6), allowing for a rapid reintroduction of regular diet. The mean postoperative hospital stay was 6.4 +/- 2.7 days (range, 4-15). CONCLUSIONS: Elective laparoscopic colectomy for diverticulitis is feasible in most cases. In most cases, the operative risk is low and the postoperative course is uneventful. Elective sigmoid laparoscopic colectomy should be considered a good therapeutic option for symptomatic diverticulitis.

Adult↗
PubMed1999

[Laparoscopic cholecystectomy in acute cholecystitis].

PURPOSE: To determine the feasibility, operative risk and patients' benefit of laparoscopy in emergency cholecystectomy for acute calculous cholecystitis. PATIENTS AND METHODS: From January 1991 to December 1998, 234 patients with acute calculous cholecystitis were operated on by emergency laparoscopic cholecystectomy. There were 131 women and 103 men (mean age: 57 years), (Asa 2: 48%, Asa 3: 10%). In seven patients, choledocolithiasis was detected by endoscopic ultrasonography and preoperatively treated by endoscopic sphincterotomy. The mean delay between in-hospital admission and cholecystectomy was 20 hours (2-160). Cholecystectomy was performed with primary approach of Calot's triangle. Intraoperative cholangiography, selectively performed (n = 70), detected choledocolithiasis in three patients. RESULTS: The mean duration of surgery was 149 minutes (62-313). The conversion rate was 13% and decreased through the years. The postoperative complication rate was 18%. Eight patients (3.4%) had an abdominal complication. One patient (0.4%) died of bile peritonitis after intraoperative undetected main bile duct injury. The mean postoperative hospital stay was 6.04 days. It was 3.5 days only, very old patients and those with severe associated disease being excluded. CONCLUSION: Laparoscopy appears to be a good approach for emergency cholecystectomy in patients with acute calculous cholecystitis.

Acute Disease↗
PubMed1999

Use of diagnostic clusters to assess the economic consequences of rhinopharyngitis in children in Italy and France during the winter. Rhinitis Survey Group.

To determine how practitioners diagnose rhinopharyngitis (RP), we conducted a longitudinal, multicenter study of a cohort of 900 children, collecting medical and economic data without interfering with usual medical practice during the winter of 1996-1997 in France and Italy. All ear, nose, and throat (ENT) infections were described clinically; data on the consumption of medical items (physician visits, drug treatment, hospitalization, physiotherapy, preventive treatment, laboratory tests, roentgenograms, and outpatient procedures) were collected to estimate the cost of caring for patients with RP. The mean age of the children was 28.0 months, and the ratio of males to females was approximately 5 to 4. Patients had had a mean 4.1 episodes of RP the previous year and 1.4 episodes of acute otitis media (AOM). There were no marked differences in the children's characteristics between France and Italy. During the winter of the study, this population experienced 4.26 episodes of ENT infection, of which 73.5% were documented at the study sites. Seven homogeneous groups of RP were found, 2 of them each representing <4% of the overall population. One group presented with otalgia, although the diagnosis of AOM was not recorded by the physician. In 4 groups, the presence of nasal discharge plus cough (without otalgia) was used to make the diagnosis. Medical item consumption varied by country and by group of RP, mainly in the prevailing choice of antibiotics. The difference in duration of treatment was not statistically significant. As a consequence, the costs of caring for patients with RP varied greatly, RP with AOM being the most costly. Last, prognostic factors for costly episodes of infectious ENT were identified. The population at risk included young children who had had AOM episodes during the previous winter, had a first episode of AOM before 6 months of age, had a history of AOM associated with effusion, or attended a community-based child care facility. Therefore, clinical trials aimed at demonstrating cost-effectiveness of prophylaxis should focus on this population.

Analysis of Variance↗
PubMed1999

Laparoscopic cystogastrostomy for pancreatic pseudocyst is safe and effective.

Between March 1997 and March 1998, three consecutive patients underwent laparoscopic cystogastrostomy for persistent giant retrogastric pancreatic pseudocyst complicating an attack of acute pancreatitis. The mean cyst diameter was 15 +/- 1 cm (range 14-16). The procedure was performed with four trocars. The anterior wall of the stomach was opened longitudinally. The pseudocyst was entered through the posterior wall of the stomach. A cystogastrostomy was created by suturing the margins of the communication by interrupted nonabsorbable sutures. The mean operative time was 123 +/- 15 min, and there were no postoperative complications. The mean postoperative hospital stay was 4 +/- 1 days. Computed tomography demonstrated complete resolution of the pseudocyst. Laparoscopic cystogastrostomy represents a good therapeutic option for persistent retrogastric pancreatic pseudocyst.

Acute Disease↗
PubMed1998

Activity of the delta-opioid receptor is partially reduced, whereas activity of the kappa-receptor is maintained in mice lacking the mu-receptor.

Previous pharmacological studies have indicated the possible existence of functional interactions between mu-, delta- and kappa-opioid receptors in the CNS. We have investigated this issue using a genetic approach. Here we describe in vitro and in vivo functional activity of delta- and kappa-opioid receptors in mice lacking the mu-opioid receptor (MOR). Measurements of agonist-induced [35S]GTPgammaS binding and adenylyl cyclase inhibition showed that functional coupling of delta- and kappa-receptors to G-proteins is preserved in the brain of mutant mice. In the mouse vas deferens bioassay, deltorphin II and cyclic[D-penicillamine2, D-penicillamine5] enkephalin exhibited similar potency to inhibit smooth muscle contraction in both wild-type and MOR -/- mice. delta-Analgesia induced by deltorphin II was slightly diminished in mutant mice, when the tail flick test was used. Deltorphin II strongly reduced the respiratory frequency in wild-type mice but not in MOR -/- mice. Analgesic and respiratory responses produced by the selective kappa-agonist U-50,488H were unchanged in MOR-deficient mice. In conclusion, the preservation of delta- and kappa-receptor signaling properties in mice lacking mu-receptors provides no evidence for opioid receptor cross-talk at the cellular level. Intact antinociceptive and respiratory responses to the kappa-agonist further suggest that the kappa-receptor mainly acts independently from the mu-receptor in vivo. Reduced delta-analgesia and the absence of delta-respiratory depression in MOR-deficient mice together indicate that functional interactions may take place between mu-receptors and central delta-receptors in specific neuronal pathways.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1998

Involvement of delta-opioid receptors in the effects induced by endogenous enkephalins on learned helplessness model.

Pharmacological, neurochemical and behavioural findings support a possible role of endogenous opioids in clinical depression. There is evidence from animal studies that delta-opioid receptors are involved in several behavioural responses to opioids, including motivational activities. In the present study, the mixed enkephalin catabolism inhibitor, RB 101 (N(R,S)-2-benzyl-3[(S)-(2-amino-4-methylthiobutyldithio]-1-oxoprop yl)-L-phenylalanine benzyl ester) (1.25, 2.5 and 5 mg/kg), induced a dose-dependent antidepressant-like effect in a learned helplessness model. Thus, RB 101 reversed escape deficits in rats previously subjected to inescapable shocks, suggesting the involvement of endogenous enkephalins in depression. Similar effects were observed after administration of the selective delta-opioid receptor agonist, BUBU (Tyr-D.Ser-(O-tert-butyl)-Gly-Phe-Leu-Thr(O-Tet-butyl-OH) (1 and 2 mg/kg). Moreover, RB 101 effects were antagonized by administration of naltrindole (NTI) (0.1 mg/kg), which points to a preferential involvement of delta-opioid receptors in this enkephalin-controlled behaviour. As RB 101 has been reported to be almost devoid of opiate-related side-effects, it could represent a promising alternative in the treatment of depressive patients who are unresponsive to, or intolerant of, classical antidepressants.

Analgesics↗
PubMed1998

In vitro inhibition of human colonic motility with SR 59119A and SR 59104A: evidence of a beta3-adrenoceptor-mediated effect.

The new beta3-adrenoceptor is present in the gastrointestinal tract of various species. This study aimed to show that this receptor modulates human colonic motility in vitro. We used circular muscle strips from the human colon suspended in single organ baths containing Krebs solution and subjected to an initial 1.5-2 g tension. We measured the effects of different beta3-adrenoceptor agonists, including SR 59104A (N-[(6-hydroxy-1,2,3,4-tetrahydronaphthalen-(2R)-2-yl)methyl]-(2 R)-2-hydroxy-2-(3-chlorophenyl)ethanamine hydrochloride), SR 59119A (N-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-(2R)-2-yl)methyl]-(2R) -2-hydroxy-2-(3-chlorophenyl)ethanamine hydrochloride), BRL 37344 (R,R + S,S) [4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino] propyl] phenoxy] acetic acid), and of isoprenaline and salbutamol in the absence or in the presence of propranolol alone or in combination with the beta3-adrenoceptor antagonist SR 59230A (3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydro-naphthalen-1- ylamino]-(2S)-2-propanol oxalate) on amplitude of spontaneous contractions. To evaluate a possible beta2-adrenoceptor-mediated effect, we studied the action of these compounds on human isolated bronchi. On the human isolated colon, SR 59119A, SR 59104A and isoprenaline reduced the initial amplitude of spontaneous contractions by 60%. The curves obtained in the presence of antagonists suggested an action mediated by beta3-adrenoceptor stimulation, since propranolol did not antagonize the action of SR 59119A and SR 59104A, whereas the combination of propranolol and SR 59230A significantly displaced the concentration-response curve of these agonists to the right. This study provides pharmacological evidence of modulation of human colonic motility, and especially of the amplitude of spontaneous contractions, by the atypical beta-adrenoceptor, the beta3-adrenoceptor.

Adrenergic beta-Agonists↗
PubMed1998

Disruption of the kappa-opioid receptor gene in mice enhances sensitivity to chemical visceral pain, impairs pharmacological actions of the selective kappa-agonist U-50,488H and attenuates morphine withdrawal.

***micro***-, delta- and kappa-opioid receptors are widely expressed in the central nervous system where they mediate the strong analgesic and mood-altering actions of opioids, and modulate numerous endogenous functions. To investigate the contribution of the kappa-opioid receptor (KOR) to opioid function in vivo, we have generated KOR-deficient mice by gene targeting. We show that absence of KOR does not modify expression of the other components of the opioid system, and behavioural tests indicate that spontaneous activity is not altered in mutant mice. The analysis of responses to various nociceptive stimuli suggests that the KOR gene product is implicated in the perception of visceral chemical pain. We further demonstrate that KOR is critical to mediate the hypolocomotor, analgesic and aversive actions of the prototypic kappa-agonist U-50, 488H. Finally, our results indicate that this receptor does not contribute to morphine analgesia and reward, but participates in the expression of morphine abstinence. Together, our data demonstrate that the KOR-encoded receptor plays a modulatory role in specific aspects of opioid function.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗