[Smears, HPV tests, vaccinations: their role in the future].
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Biomedical subjects
Publications and source records attributed to S Vincent.
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BACKGROUND AND OBJECTIVE: The aim of this study was to assess target-controlled propofol infusion as a technique of sedation for shoulder surgery under interscalene brachial plexus block in the sitting position and to evaluate the effect of sedation on hypotensive/bradycardic events during this procedure. METHODS: One hundred and forty patients undergoing elective shoulder surgery in the sitting position under interscalene brachial plexus block (with 30 mL of ropivacaine 0.75%) were prospectively enrolled. All patients were premedicated with hydroxyzine 1 mg kg(-1), none received beta-blockers. No patients were given atropine except for the patients who experienced a vasovagal event either during the block procedure or intravenous catheter placement. The target-controlled propofol infusion was started immediately after positioning the patient on the operating table. The initial target concentration was 1 microg mL(-1). The infusion rate was adjusted every 15 min by increasing or decreasing the target concentration by 0.2 microg mL(-1) steps to maintain the patient rousable to verbal commands (score of 3 on Wilson sedation scale). The following parameters were assessed: minimal, maximal, optimal target concentration, respiratory and haemodynamic parameters, total propofol dose, additional alfentanil needs, occurrence of hypotensive/bradycardic events, complications. Results are mean +/- SD. Statistical analysis used t-test and chi2-tests. RESULTS: The optimal propofol target concentration was 0.8 mug mL(-1). No respiratory complications or conversion to general anaesthesia was reported. Two patients experienced transient and inconsequential intraoperative agitation. The incidence of hypotensive/bradycardic events during the procedure was 5.7% (eight patients). CONCLUSION: Target-controlled propofol infusion (0.8-0.9 microg mL(-1)) following hydroxyzine premedication is a safe and effective technique for sedation when combined with interscalene brachial plexus block during shoulder surgery in the sitting position.
OBJECTIVE: The study aimed to characterize the lipid and apolipoprotein profile and the prevalence of cardiovascular risk factors in a population of urban adult women of Morocco. DESIGN: A total of 213 women 25-55 y old were sampled from an agricultural province of Morocco: El Jadida. The following parameters of lipid and apolipoprotein profile were measured: plasma triglycerides (TG), plasma cholesterol (TC), triglyceride-rich lipoprotein triglycerides (TRL-TG), TRL-cholesterol (TRL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoproteins A1, B, B48, CIII and E. Waist circumference (WC), body mass index (BMI) and blood pressure (BP) were also determined. RESULTS: The women studied showed the following pattern: elevated TC, LDL-C levels and TC/HDL-C in 10, 19.4 and in 43.8%, respectively; low HDL-C levels in 45.3% (<0.9 mmol/l) or in 95% (when the cutoff <1.3 mmol/l is used), elevated TG levels in 11.8%. Elevated TRL-C (>0.6 mmol/l) and TRL-TG (>0.8 mmol/l) were observed in 13.4%. Obesity and hypertension were highly prevalent in 23.9 and 16.5%, respectively. Plasma triglyceride concentrations were closely correlated with plasma concentrations of TRL-TG (R = 0.86, P = 0.0001), apoB (R = 0.50, P = 0.0001) and apoCIII (R = 0.52, P = 0.0001) and moderately correlated with HDL-C levels (R = -0.3, P = 0.0001) and BMI (R = 0.4, P = 0.0001). The association between BMI and systolic blood pressure was statistically significant (R = 0.3, P = 0.0001). Obesity, BP, TRL-C, TRL-TG, TG, apoB and apoCIII increased with age. CONCLUSION: There is a high prevalence of some risk factors for cardiovascular disease including altered lipid and lipoprotein profiles in the Moroccan urban women studied, some of these risk factors are associated with age.
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OBJECTIVE: To report the rationale, recruitment, design, dietary intervention and baseline characteristics of participants in the Medi-RIVAGE study (Mediterranean Diet, Cardiovascular Risks and Gene Polymorphisms). DESIGN: A randomised, parallel trial comparing a new nutritional programme with a conventional programme. SETTING: Centre for Detection and Prevention of Arteriosclerosis, Timone University Hospital, Marseille, France, and collaborating teams. SUBJECTS: Two hundred and twelve male and female volunteers with at least one cardiovascular risk factor. INTERVENTION: A Mediterranean-type diet characterised mainly by the quality of fatty acids, amount of fish, vegetable foodstuffs and fibre was proposed and compared with a usually prescribed, low-fat/cholesterol diet. Body mass index, fasting lipids and lipoproteins, apolipoproteins, glucose, insulin and homocysteine were the main outcome measures. Gene polymorphisms of interest were determined. RESULTS: Characteristics of men in the two arms were comparable with regard to sociodemographic variables, and clinical and biological cardiovascular risk factors. There were few differences between the groups of women (cholesterol-related parameters, P<0.05). There was no difference between arms in allelic distribution of the gene polymorphisms studied. Saturated fat and protein intakes were high while carbohydrate and fibre intakes were low, but with no difference between arms. Overall, the nutritional markers were comparable in both arms with few exceptions. Correlations between nutritional intakes and plasma nutrient levels ranged from 0.19 (beta-carotene) to 0.47 (folate). CONCLUSIONS: The comparability of the two arms is notable and warrants a low risk of biases. Current diet departs from the traditional Mediterranean one. The assessment of nutritional intake is validated by correlations obtained between dietary intake and relevant biomarkers. This will be important to estimate participant compliance and to analyse intervention data.
In France, organization of the cytopathology seems to be quite different from that specifically regulated in the USA and in some other European countries. The aim of this article is to underline these specificities and to describe the solutions we advocate concerning new technologies, teaching, quality assurance, national guidelines em leader, to make our current practice compatible with the international recommendations. Moreover, we highlight the peculiar status of French cytotechnologists' and comment on the recent dramatic decrease of the medical demography in France, the consequence of which may promote a controlled transfer of competence.
Survey was conducted, in the different forests ecosystems of Western Ghats of Tamil Nadu in Nilgris, Coimbatore, Erode, Virudhunagar and Tirunelveli districts to collect the adult spiders and study them taxonomically. Fifty-six species of spider collections were made. From the fifty six, biology was studied for six spider species, such as Micrommata virescens n.sp., Oxyopes javanus, Peucetia virridana, Agelena kariansholensis n.sp., Heteropoda venatoria and Olios hampsoni. Biology studies with Peucetia virridana and Micrommata virescens showed that both species took more than 350 days to complete their life cycles. Heteropoda venetoria and Oxyopes javanus took more than 250 days to complete their life cycle. Agelena kariansholensis took 381 days and Olios hampsoni took 345 days to complete their life cycles. 30% of Peucetia virridana and more than 20% of Heteropoda venatoria and Micrommata virescens and 7% of Oxyopes javanus developed into adults in captivity.
Vpu is an 81 amino acid protein of HIV-1 with two phosphorylation sites. It consists of a short N-terminal end traversing the bilayer and a longer cytoplasmic part. The dual functional role of Vpu is attributed to these topological distinct regions of the protein. The first 52 amino acids of Vpu (HV1H2) have been simulated, which are thought to be embedded in a fully hydrated lipid bilayer and to consist of a transmembrane helix (helix-1) connected via a flexible linker region, including a Glu-Tyr-Arg (EYR) motif, with a second helix (helix-2) residing with its helix long axis on the bilayer surface. Repeated molecular dynamics simulations show that Glu-28 is involved in salt bridge formation with Lys-31 and Arg-34 establishing a kink between the two helices. Helix-2 remains in a helical conformation indicating its stability and function as a "peptide float," separating helix-1 from the rest of the protein. This leads to the conclusion that Vpu consists of three functional modules: helix-1, helix-2, and the remaining residues toward the C-terminal end.
1. The metabolism of a substituted 2,4-thiazolidinedione (P1) with dual PPARalpha/gamma activity was evaluated in male and female rats, dogs and monkeys. A para-hydroxylated metabolite (M1) with potent PPARgamma-selective agonist, was a major circulating drug-related component in female rats, dogs and monkeys, but not in male rats (M1-to-P1 exposure ratio of <1, 3-5, 5 and 5-11 in male rat, monkey, female rat, and dog, respectively). 2. M1 (%) formed in vitro (5, 53, 57-65, 67 and 67% in male rat, monkey, female rat, dog, and human liver microsomes, respectively), rank ordered with M1 (%) formed in vivo (24-45, 53-57, 78, 75-85%, for male rat, monkey, female rat and dog, respectively, after oral administration of P1). 3. The plasma clearance of M1 was higher in male rats (32 ml min(-1) kg(-1) compared with 6, 7 and 2 ml min(-1) kg(-1) in female rat, male monkey and male dogs, respectively). 4. The low amounts of M1 observed in male rats, with the appearance of products of the cleavage of the propyl group between the phenyl groups was probably due to the presence of the sex-specific CYP2C11, which cleaves P1 at the propyl bridge. None of the CYPs present in female rats cleaved P1 at this site and M1 was only produced by CYP2C6. In humans, only CYP2C8 and the polymorphic CYP2C19 produced M1.
AIM: We have explored in the following study the glucoregulatory responses (glycemia, insulinemia, catecholamines) at the end of 2 supramaximal tests of different durations. METHODS: Seven untrained male subjects (21.9+/-0.3 y) performed an isolated exercise of 6 s (T6) and a Wingate-test of 30 s. To determine the levels of lactate (La), plasma concentrations of glucose, insulin, adrenaline (A) and noradrenaline (NA), blood samples have been collected successively at rest, after a warm-up period of 15 min, immediately after T6 and T30, and after 5, 10, 20, and 30 min of recovery. RESULTS: Whether expressed as absolute or relative values, the peak power recorded during the 2 tests is statistically the same in T6 and T30. The maximal value of lactate (L(amax)) measured 5 min after the end of the 2 exercises is significantly greater after T30 (12.3+/-0.9 mmol x L(-1)) than after T6 (5.4+/-0.4 mmol x L(-1)) and T30 (4.2+/-0.2 mmol x L(-1)). No significant difference is observed between the plasma glucose concentrations recorded after the 2 tests until the first 10 min of recovery. However the plasma glucose values recorded after 20 and 30 min of recovery are significantly higher after T6 than after T30. Whatever the duration of the test, the insulinemia level remains unchanged at the end of the exercise and during the 30 min of recovery. On the other hand, the values of adrenaline and noradrenaline after T6 and T30 become considerably higher than those recorded at rest. However, the increase remains significantly higher after T30 (13.5+/-1.8 nmol x L(-1) for NA and 2.7+/-0.7 nmol x L(-1) for A) than after T6 (4.9+/-0.3 nmol x L(-1) for NA and 1.2+/-0.2 nmol x L(-1) for A). CONCLUSION: These results suggest that the mechanism responsible for increasing blood glucose surpass those which decrease it during supramaximal exercise. However, plasma glucose concentrations is affected by the duration of supramaximal exercise. The lower increase of plasma glucose concentration after T30 than after T6 might be explained by the resting of muscle glycogen stores which are more used during T30 than after T6, but in the absence of muscle glycogen content measurement we cannot conclude.
It has been well demonstrated that the principal factor responsible for oxidative damage during exercise is the increase in oxygen consumption. However, other theoretical factors (acidosis, catecholamine autoxidation, ischemia-reperfusion syndrome, etc.) that are known to induce, in vitro, oxidative damage may also be operative during short-term supramaximal anaerobic exercise. Therefore, we hypothesized that short-term supramaximal anaerobic exercise (30-s Wingate test) could induce an oxidative stress. Lipid peroxidation markers [serum lipid radical production detected by electron spin resonance (ESR) spectroscopy and plasma malondialdehyde (MDA) levels detected by the thiobarbituric acid reactive substances (TBARS) method], as well as erythrocyte antioxidant enzyme activities [glutathione peroxidase (GPx), superoxide dismutase (SOD)] and erythrocyte glutathione (GSH) levels, were measured at rest, after the Wingate test and during the 40 min of recovery. The recovery of exercise was associated with a significant increase (x2.7) in lipid radical production detected by ESR spectroscopy, as well as with changes in the erythrocyte GSH level (-13.6%) and SOD activity (-11.7%). The paradoxical decrease in plasma TBARS (-23.7%) which was correlated with the peak power developed during the Wingate test ( r=-0.7), strongly suggests that such exercise stimulates the elimination of MDA. In conclusion, this study demonstrates that short-term supramaximal anaerobic exercise induces an oxidative stress and that the plasma TBARS level is not a suitable marker during this type of exercise.
The aim of this study was to verify if, as for men, training status induces different catecholamine responses to exercise. To do this, we investigated the effect of training status (sprint or endurance) on plasma catecholamine response to a supramaximal exercise in women. Nineteen subjects took part in our study: six untrained subjects (UT), seven endurance trained subjects (ET) and six sprint trained ones (ST). The trained subjects (ET and ST) were all competing at a high national level. The maximal power (W max ) and the mean power (W) were determined from the Wingate-test. Blood lactate, adrenaline (A) and noradrenaline (NA) were analysed at rest (La 0, A 0 and NA 0 ), immediately at the end of the exercise (A max and NA max ) and after 5 min recovery (La max [3 min in arterialized blood], A 5 and NA 5 ). The disappearance of A and NA was judged by the ratio (A max -A 5 )/A max and (NA max -NA 5 )/NA 5. The ratio A max /NA max was considered as an index of the adrenal medulla responsiveness to the sympathetic nervous activity. As expected, during the Wingate-test ST exhibited significantly higher performances compared to UT and ET. But in contrast to the men's data no difference was observed between the three groups both for La max (13.1 +/- 0.8 mmol x L (-1); 14.8 +/- 1.0 mmol x L (-1) and 11.2 +/- 0.5 mmol x L (-1) respectively for ET, ST and UT), NA max (22.1 +/- 1.2 nmol x L (-1); 13.1 +/- 2.4 nmol x L (-1) and 20.2 +/- 7 nmol x L (-1)respectively for ET, ST and UT) and A max (4.1 +/- 0.8 nmol x L (-1); 2.6 +/- 0.6 nmol x L (-1); 13.1 +/- 0.6 nmol x L (-1) respectively for ET, ST and UT). Consequently the ratio A max /NA max was similar in UT, ET and ST (respectively 0.2 +/- 0.03; 0.2 +/- 0.04; 0.17 +/- 0.04), These results indicated, in contrast to the men's data, that the catecholamine response to the Wingate-test did not differ between female subjects of different status of training. In conclusion this study did not find any significant effect of training status on the catecholamine response to supramaximal exercise and so argues in favour of sex differences in response to training.
Catla catla, under the sublethal stress of cadmium exhibited depletion in food utilization parameters and it was concentration dependent. Heavy metal intoxication was found to exhibit reduction in biomass.
The presence of the iron-binding protein lactoferrin (Lf) in some specific areas of the central nervous system and particularly in the normal human substantia nigra, where it is found in dopaminergic (DA) neurons and some glial cells, led us to investigate Lf synthesis in this area. Lf mRNA were identified using in situ hybridization and found in small ameboid cells. These cells were identified using immunocytochemistry as activated microglia since they exhibited macrophage markers such as the CD68 and the CR1 antigens. Double immunofluorescent labeling confirmed that the two Lf immunostained cell populations were activated microglia and DA neurons. Since activated microglia contained both Lf and its messenger, these cells are the Lf producing cells. The presence of Lf in DA neurons in which no Lf messengers were visible, might be due to an endocytosis mechanism, DA neurons probably internalizing Lf produced in microglial cells located in their neighborhood. In neuropathological disorders, such as Alzheimer's and Parkinson's diseases, inflammatory process and oxidative stress are events that contribute to neuronal death. Since Lf concentration increases during these pathologies, we studied the level of Lf expression under these different stresses and showed, using RT-PCR, that the immortalized human embryonic microglial CHME cell line produced Lf transcripts under tumor necrosis factor alpha or 1-methyl-4-phenylpyridinium treatment whereas untreated cells did not. These data confirm that Lf is produced only when microglia are activated.
Directed screening of a carboxylic acid-containing combinatorial library led to the discovery of potent inhibitors of the integrin VLA-4. Subsequent optimization by solid-phase synthesis afforded a series of sulfonylated dipeptide inhibitors with structural components that when combined in a single hybrid molecule gave a sub-nanomolar inhibitor as a lead for medicinal chemistry. Preliminary metabolic studies led to the discovery of substituted biphenyl derivatives with low picomolar activities. SAR and pharmacokinetic characterization of this series are presented.
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Extensive development of the structure-activity relationships of a screening lead determined three important pharmacophores for gonadotropin-releasing hormone (GnRH) receptor antagonist activity. Incorporation of the 3,4,5-trimethylphenyl group at the 3-position, 2-(2(S)-azetidinyl)ethoxy group at the 4-position, and N-4-pyrimidinylcarboxamide at the 6-position of the quinolone core resulted in the identification of 4-(2-(azetidin-2(S)-yl)ethoxy)-7-chloro-2-oxo-3-(3,4,5-trimethylphenyl)-1,2-dihydroquinoline-6-carboxylic acid pyrimidin-4-ylamide (1) as a potent antagonist of the GnRH receptor. A 10(4)-fold increase in in vitro binding affinity is observed for the GnRH receptor as compared to the initial screening lead. Compound 1 exhibits nanomolar binding activity and functional antagonism at the human receptor and is 7-fold less active at the rhesus receptor. Intravenous administration of compound 1 to rhesus monkeys results in a significant decrease of the serum levels of downstream hormones, luteinizing hormone (79% decrease in area under the curve) and testosterone (92% decrease in area under the curve), at a dose of 3 mg/kg. Quinolone 1 is a potent nonpeptidyl antagonist for the human GnRH receptor that is efficacious for the suppression of luteinizing hormone and testosterone in primates.