Showing papers by "Rhône-Poulenc published in 2001"
TL;DR: Assessment of the maternal, fetal and neonatal safety of enoxaparin in pregnant women who require antithrombotic therapy and its use in women with high blood pressure finds it to be safe.
275 citations
TL;DR: The results of the present study indicate that morphine did not induce intravenous self-administration in mutant CB1 receptor knockout mice, whereas it was significantly self- Administered by the corresponding wild type mice.
263 citations
TL;DR: The main aims of the workshop were to seek a consensus on the current models of the intestinal barriers and ways to screen for the movement of drugs across this barrier, and to make useful recommendations for the promotion of the three Rs in this area as discussed by the authors.
Abstract: The principal aims of the workshop were to seek a consensus on the current models of the intestinal barriers and ways to screen for the movement of drugs across this barrier,and to make useful recommendations for the promotion of the three Rs in this area.
207 citations
TL;DR: In this article, a calibration procedure to monitor supersaturation from FTIR measurements is presented, and the technique is used to develop efficient procedures for the determination of solubility: and metastability curves.
157 citations
TL;DR: The use of the NOEC should be phased out and that a regression-based estimation procedure should be used, and ECx, derived with existing test guidelines, whose lowest bounds of the confidence interval are on average similar to present NOEC would improve this approach by a priori encouraging more precise experiments.
135 citations
TL;DR: In this article, acoustic emission was used to study the development of pitting corrosion on AISI 316L austenitic stainless steel, in a 3% NaCl solution acidified to pH 2.
124 citations
TL;DR: In most NFT-bearing neurons, a strong reduction in acetylated alpha-tubulin immunoreactivity and a reduction of the in situ hybridization signal for tubulin mRNA are observed, consistent with the hypothesis that destabilization of the microtubule network is an important mechanism of cell dysfunction in Alzheimer's disease.
Abstract: Neurofibrillary tangles (NFTs) are a characteristic neuropathological lesion of Alzheimer's disease (AD). They are composed of a highly-phosphorylated form of the microtubule-associated protein tau. We are investigating the relationship between NFTs and microtubule stability and how tau phosphorylation and function is affected in transgenic models and by co-expression with beta-amyloid precursor protein and presenilins. In most NFT-bearing neurons, we observed a strong reduction in acetylated alpha-tubulin immunoreactivity (a marker of stable microtubules) and a reduction of the in situ hybridization signal for tubulin mRNA. In transfected cells, mutated tau forms (corresponding to tau mutations identified in familial forms of frontotemporal dementias linked to chromosome 17) were less efficient in their ability to sustain microtubule growth. These observations are consistent with the hypothesis that destabilization of the microtubule network is an important mechanism of cell dysfunction in Alzheimer's disease. The glycogen synthase kinase-3 beta (GSK-3 beta) generates many phosphorylated sites on tau. We performed a neuroanatomical study of GSK-3 beta distribution showing that developmental evolution of GSK-3 beta compartmentalization in neurons paralleled that of phosphorylated tau. Studies on transfected cells and on cultured neurons showed that GSK-3 beta activity controls tau phosphorylation and tau functional interaction with microtubules. Tau phosphorylation was not affected in neurons overexpressing beta-amyloid precursor protein. Transgenic mice expressing a human tau isoform and double transgenic animals for tau and mutated presenilin 1 have been generated; a somatodendritic accumulation of phosphorylated transgenic tau proteins, as observed in the pretangle stage in AD, has been observed but NFTs were not found, suggesting that additional factors might be necessary to induce their formation.
110 citations
TL;DR: It is shown that G3BP promotes S phase entry in cultured fibroblasts deprived of serum and that this function is dependent on the presence of the RNA binding domain of the protein.
85 citations
TL;DR: Pathological processes leading to reductive stress and their relief by such protective agents is reviewed and the proposed molecular mechanism is outlined.
Abstract: Reductive stress, characterised by an increased NADH:NAD+ ratio, may be as common and as important a consequence of redox imbalance as oxidative stress. It may also be an important predisposing cause of the generation of reactive oxygen species. Considerable experimental and indirect clinical evidence suggests that protection against reductive stress depends on biomolecules with electrophilic methyl groups (EMG) such as S-adenosylmethionine, betaine, carnitine and phosphatidylcholine. Pathological processes leading to reductive stress and their relief by such protective agents is reviewed and the proposed molecular mechanism is outlined. These and other EMG-containing biomolecules are part of the daily diet and may represent an important control system for redox balance.
78 citations
TL;DR: Results show clearly that the penetration of the antibiotic into the cells is favored when this latter is coupled with pyoverdin, and that the labile spacer arm adducts present much higher activity than the quinolones alone.
Abstract: Pseudomonas aeruginosa is particularly resistant to most all the antibiotics presently available, essentially because of the very low permeability of its outer membrane. To overcome this, we synthesized four siderophore-based antibiotics formed by two quinolones - norfloxacin and benzonaphthyridone - bound to the pyoverdin of P. aeruginosa ATCC 15692 via two types of spacer arms: one stable and the other readily hydrolyzable. From the comparison of their antibacterial properties with those of the two unbound quinolones, we reached the following conclusions: (a) The adducts inhibit Escherichia coli's gyrase showing that the dissociation of the compounds is not necessary for their activity. However, the presence of the pyoverdin moiety on the molecule decreases the inhibition activity compared to the antibiotic alone. (b) They facilitate the uptake of (55)Fe using the specific pyoverdin-mediated iron-transport system of the bacterium. No uptake was observed either with P. aeruginosa ATCC 27853, which produces a structurally different pyoverdin, or with P. aeruginosa K690, which is a mutant of P. aeruginosa ATCC 15692 lacking FpvA, the outer-membrane pyoverdin receptor. (c) MIC determinations have shown that only strains P. aeruginosa ATCC 15692 and the derived outer-membrane receptor-producing but pyoverdin-deficient P. aeruginosa IA1 mutant present higher susceptibility to the pyoverdin-quinolone adducts, whereas P. aeruginosa ATCC 27853 and K690 are much more resistant. (d) Growth inhibition by these adducts confirmed these results and showed that the adducts with the hydrolyzable spacer arm have better activity than those with the stable one and that the labile spacer arm adducts present much higher activity than the quinolones alone. These results show clearly that the penetration of the antibiotic into the cells is favored when this latter is coupled with pyoverdin: Only the strains possessing the appropriate outer-membrane receptor present higher susceptibility to the adduct. In this case the antibiotic uses the pyoverdin-mediated iron-transport system. Furthermore, better efficiency is obtained when the spacer arm is labile and favors the antibiotic release inside the cell, allowing better inhibition of gyrase.
77 citations
TL;DR: Results suggest that one of the enzymes involved in toluene degradation is responsible for this allylic monohydroxylation in the form of enantiomerically pure (+)trans-carveol and traces of (+) carvone.
Abstract: The toluene-degrading strain Rhodococcus opacus PWD4 was found to hydroxylate d-limonene exclusively in the 6-position, yielding enantiomerically pure (+)trans-carveol and traces of (+) carvone This biotransformation was studied using cells cultivated in chemostat culture with toluene as a carbon and energy source The maximal specific activity of (+) trans-carveol formation was 147 U (g of cells [dry weight])−1, and the final yield was 94 to 97% Toluene was found to be a strong competitive inhibitor of thed-limonene conversion Glucose-grown cells did not form anytrans-carveol from d-limonene These results suggest that one of the enzymes involved in toluene degradation is responsible for this allylic monohydroxylation Another toluene degrader (Rhodococcus globerulus PWD8) had a lower specific activity but was found to oxidize most of the formedtrans-carveol to (+) carvone, allowing for the biocatalytic production of this flavor compound
TL;DR: In this paper, the dispersion of alumina-coated TiO2 particles by adsorption of the sodium salt of poly(acrylic) acid (PANa) was investigated in regard to the effective charge number of the particles.
TL;DR: The superior performance of the OQLQ in terms of administration time, missing responses, and discriminatory capacity needs to be weighed against the advantages of using a self-administered instrument such as the QUALEFFO.
Abstract: Introduction: Studies comparing the performance of health-related quality of life instruments in osteoporosis are lacking. We compared the feasibility, validity and reliability of the osteoporosis quality of life questionnaire (OQLQ) and the QUALEFFO (test version) in women with vertebral deformities due to osteoporosis. Methods: Three hundred and thirty-eight patients diagnosed with primary osteoporosis and vertebral deformity and a random sample of 304 women from the general population (control group) were recruited. Patients and controls were randomly assigned to receive either the OQLQ or the QUALEFFO, and the SF-36 and EQ-5D. Test–retest reliability was assessed in the patient group. Results: The QUALEFFO had more items with missing data and took slightly longer to administer (20.7 vs. 18.7 min). Cronbach's α and intraclass correlation coefficient (ICC) values for OQLQ domains (α: 0.75–0.91; ICC: 0.85–0.93) were slightly higher than for the QUALEFFO (α: 0.63–0.90; and ICC: 0.80–0.93). OQLQ and QUALEFFO domain scores correlated as expected with SF-36 and EQ-5D domains. Both questionnaires discriminated between patients and controls though the OQLQ showed slightly better discriminant power. Discussion: The superior performance of the OQLQ in terms of administration time, missing responses, and discriminatory capacity needs to be weighed against the advantages of using a self-administered instrument such as the QUALEFFO. A full comparison also requires data on sensitivity to change.
TL;DR: Different ternary moving bed configurations are studied by determining the working flow-rates of the equivalent true moving bed at the low solvent consumption point using equilibrium theory using linear adsorption isotherms.
TL;DR: In this article, the experimental study of bubble column hydrodynamics is devoted to the experimental analysis of bubble columns hydroynamics, where a bubble column flow was performed in a vertical rectangular channel, at liquid velocities of approximately 0.10 m / s and high void fractions.
TL;DR: In this paper, the authors investigated the monitoring of pitting corrosion by the acoustic emission (AE) technique, for pits developed by potentiostatic or galvanostatic polarization on two types of 316L austenitic stainless steels, in a 3% NaCl solution acidified to pH 2.
Abstract: This experimental work was aimed at investigating the monitoring of pitting corrosion by the acoustic emission (AE) technique, for pits developed by potentiostatic or galvanostatic polarization on two types of 316L austenitic stainless steels, in a 3% NaCl solution acidified to pH 2. The study of the evolution of AE global activity during the test showed the existence of a time delay before pits became emissive. This time delay and the AE events number rate measured during the propagation step of the pits are closely correlated with the sensitivity of the material towards pitting and with the polarization procedure. Moreover, the evolution of cumulative % of AE signals number versus selected acoustic parameters shows that rise time and counts number of signals appear to be discriminating acoustic parameters for monitoring pitting corrosion of austenitic stainless steels by acoustic emission technique in our experimental conditions, whatever the polarization procedure and the type of tested steel.
TL;DR: Cell breakage techniques were studied to generate Ralstonia eutropha and waste activated sludge lysates and to evaluate their biodegradability and a reduction of 37% of the excess sludge was obtained without altering the purification yield of the process.
TL;DR: The findings of this study are very similar to those from other parts of the world, providing evidence that the factor structure for the symptoms of schizophrenia is relatively resistant to cultural influences, particularly true for negative symptoms.
TL;DR: The development of cascade and sequential processes comprising the formation of allylic azides, from aryl/heteroaryl/vinyl halides, allene and sodium azide, by palladium catalysed anion capture, followed by 1,3-dipolar cycloaddition gives rise to a variety of new triazoles in good yield.
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TL;DR: Anesthetic agents are used in laboratory animals to prevent pain or distress due to an experimental procedure or for restraint to facilitate a technically difficult procedure as mentioned in this paper, and they can be used for various applications.
Abstract: Anesthetic agents are used in laboratory animals to prevent pain or distress due to an experimental procedure or for restraint to facilitate a technically difficult procedure. This unit provides three basic protocols: injectable anesthesia for mouse, rat, and hamster; inhalant anesthesia using methoxyflurane for mouse, rat, and hamster; and injectable anesthesia using ketamine/xylazine for rabbit. An Alternate Protocol describes sedation using butorphanol/acetylpromazine in the rabbit. The Commentary further describes and compares these methods of anesthesia for various applications.
TL;DR: Ebastine at doses up to five times the recommended therapeutic dose did not cause clinically relevant changes in QTc interval, and terfenadine caused a 14.1 ms increase which was significantly different from the other three treatments.
Abstract: Aims The objective of this study was to compare the effects of high doses of ebastine with terfenadine and placebo on QTc.
Methods Thirty-two subjects were randomly assigned to four treatments (ebastine 60 mg day−1, ebastine 100 mg day−1, terfenadine 360 mg day−1, placebo) administered for 7 days. Serial ECGs were performed at baseline and day 7 of each period. QT interval was analysed using both Bazett (QTcB) and Fridericia (QTcF) corrections.
Results Ebastine 60 mg (+ 3.7 ms) did not cause a statistically significant change in QTcB compared with placebo (+ 1.4 ms). The mean QTcB for ebastine 100 mg was increased by + 10.3 ms which was significantly greater than placebo but was significantly less (P < 0.05) than with terfenadine 360 mg (+ 18.0 ms). There were no statistically significant differences in QTcF between ebastine 60 mg (−3.2 ms) or ebastine 100 mg (1.5 ms) and placebo (−2.1 ms); although terfenadine caused a 14.1 ms increase which was significantly different from the other three treatments. The increase in QTcB with ebastine most likely resulted from overcorrection of the small drug-induced increase in heart rate.
Conclusions Ebastine at doses up to five times the recommended therapeutic dose did not cause clinically relevant changes in QTc interval.
TL;DR: DABCO was found to be especially effective for the deprotection of the N-Alloc group, resulting in short reaction times and allowing the coupling of amino acids that are unstable in unprotected forms.
TL;DR: In this paper, a hydrodynamic model of dense gas-solid flow was developed to predict the flow behavior in spouted beds, and the model was implemented into a computer program.
Abstract: A hydrodynamic model of dense gas-solid flow was developed to predict the flow behaviour in spouted beds. Constitutive equations describing the particulate solids pressure, viscosity and elasticity moduli were implemented into a hydrodynamic simulation computer program. The resulting hydrodynamic simulations agree well with experimental measurements of time-averaged particle-and-gas velocity profiles, as well as with experimental solids concentration distributions obtained from three different articles issued from the fluidization literature.
TL;DR: A network involving experts from NGOs, WHO and pharmaceutical producers was commissioned with updating estimates of need for each HAT drug for the coming years, and negotiations with potential producers of new drugs such as eflornithine.
Abstract: Human African Trypanosomiasis (HAT) is a re-emerging disease whose usual treatments are becoming less efficient because of the increasing parasite resistance. Availability of HAT drugs is poor and their production in danger because of technical, ecological and economic constraints. In view of this dramatic situation, a network involving experts from NGOs, WHO and pharmaceutical producers was commissioned with updating estimates of need for each HAT drug for the coming years; negotiations with potential producers of new drugs such as eflornithine; securing sustainable manufacturing of existing drugs; clinical research into new combinations of these drugs for first and second-line treatments; centralizing drug purchases and their distribution through a unique non-profit entity; and addressing regulatory and legal issues concerning new drugs.
TL;DR: In this article, the overall methodology used to determine the working flow-rates of a true moving bed (TMB) processing langmuirian isotherms compounds is explained.
TL;DR: The combination of gemcitabine and docetaxel administered on days 1 and 8 every 21 days was feasible and well tolerated in patients with advanced malignancies and demonstrated activity in a variety of solid tumors.
Abstract: Purpose: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and effect of drug sequence on toxicities and pharmacokinetics of the combination of gemcitabine and docetaxel. Methods: A total of 34 patients with advanced cancers were treated with gemcitabine and docetaxel on days 1 and 8 of each 21-day cycle according to the following dose escalation schedule: level 1, 800 and 30 mg/m2, respectively; level 2, 800 and 40 mg/m2; level 3, 1000 and 40 mg/m2; and level 4, 1250 and 40 mg/m2. At each dose level, at least three patients were assigned to one of the two sequences of drug administration: gemcitabine→docetaxel or docetaxel→gemcitabine. Once the MTD had been reached, six additional patients, who had received no more than one chemotherapy regimen, were enrolled to dose levels 3 and 4 (gemcitabine→docetaxel) to determine the MTD in minimally pretreated patients. Results: Neutropenia was the most frequent DLT with an overall incidence of 23.5%. Grade 3/4 neutropenia occurred in 62% of patients (8/13) who had received two or more prior chemotherapy regimens, but not at all (0/15) in patients who had received no more than one prior chemotherapy regimens (P<0.001). Additional DLTs included grade 4 diarrhea and grade 4 stomatitis in one patient each. The MTD was determined to be gemcitabine 800 mg/m2 and docetaxel 40 mg/m2 in patients who had received two or more prior chemotherapy regimens. However, minimally pretreated patients (no more than one prior chemotherapy regimen) were able to tolerate higher doses with an MTD of gemcitabine 1250 mg/m2 and docetaxel 40 mg/m2. There were no significant differences in toxicities or pharmacokinetics between the two sequences of administration. Partial and minor responses were observed in 23.5% of patients: non-small-cell lung (two of eight), gastric (two of three), head and neck (one of two), bladder (two of four) and hepatocellular cancer (one of one). Conclusions: The combination of gemcitabine and docetaxel administered on days 1 and 8 every 21 days was feasible and well tolerated in patients with advanced malignancies. The sequence of administration had no significant effect on the toxicity or pharmacokinetics of either drug. Minimally pretreated patients tolerated higher doses of this combination without significant toxicities. This schedule and combination demonstrated activity in a variety of solid tumors, and merits further evaluation.
TL;DR: The combination of docetaxel and cisplatin is active in SCCHN, but toxicity is substantial and this schedule does not appear to offer any advantage compared with conventional regimens.
TL;DR: In this article, a new ultra-sound pulsed-Doppler velocimetry (UPDV) is proposed to measure flow velocities in stirred tanks as a non-intrusive manner for laminar and turbulent regimes of Newtonian and non-Newtonian fluids.
TL;DR: In this paper, the dynamic kinetic resolution of α-haloacyl imidazolidinones with a variety of nitrogen and carbon nucleophiles has been achieved with selectivities up to 100% (d.e.).
TL;DR: Aryl boronic acids can be trapped by an ammonium hydroxide-form Dowex® Ion Exchangers resin leading to polymer-ionically bound borates and cycled into macroheterocycles under Suzuki-Miyaura coupling conditions.