Cyclic olefin copolymer plasma millireactors.

The novelty of this paper lies in the development of a multistep process for the manufacturing of plasma millireactors operating at atmospheric pressure. The fabrication process relies on the integration of metallic electrodes over a cyclic olefin copolymer chip by a combination of photopatterning and sputtering. The developed plasma millireactors were successfully tested by creating air discharges in the gas volume of the millichannel. A sputtered silica layer was deposited on the channel walls to provide a barrier between the plasma and the polymer in order to prevent the alteration of polymer surfaces during the plasma treatment. Interest in this process of employing plasma millireactor as a high reactive environment is demonstrated here by the degradation of a volatile organic compound (acetaldehyde) in ambient air. In this miniaturized device, we obtained a high acetaldehyde conversion (98%) for a specific input energy lower than 200 J L(-1).

[Amebic liver abscess and late recurrence with no travel in an endemic area]. / Abcès amibien hépatique avec récidive tardive en l'absence de séjour récent en zone d'endémie.

Amebic liver abscess is the main complication of amebic dysentery. Recurrences after treatment and apparent healing are very uncommon. The purpose of this report is to describe the case of a patient with a very late relapse of an amebic liver abscess, 10 years after the first episode. This recurrence seems due to an incomplete initial treatment. This case illustrates the reason for and importance of complying with the current therapeutic strategy: nitroimidazole followed by a luminal agent to eradicate intestinal amebic colonization.

Consumer perceptions of medication warnings about driving: a comparison of French and Australian labels.

OBJECTIVE: Little research has examined user perceptions of medication warnings about driving. Consumer perceptions of the Australian national approach to medication warnings about driving are examined. The Australian approach to warning presentation is compared with an alternative approach used in France. Visual characteristics of the warnings and overall warning readability are investigated. Risk perceptions and behavioral intentions associated with the warnings are also examined. METHOD: Surveys were conducted with 358 public hospital outpatients in Queensland, Australia. Extending this investigation is a supplementary comparison study of French hospital outpatients (n = 75). RESULTS: The results suggest that the Australian warning approach of using a combination of visual characteristics is important for consumers but that the use of a pictogram could enhance effects. Significantly higher levels of risk perception were found among the sample for the French highest severity label compared to the analogous mandatory Australian warning, with a similar trend evident in the French study results. The results also indicated that the French label was associated with more cautious behavioral intentions. CONCLUSION: The results are potentially important for the Australian approach to medication warnings about driving impairment. The research contributes practical findings that can be used to enhance the effectiveness of warnings and develop countermeasures in this area. Hospital pharmacy patients should include persons with the highest level of likelihood of knowledge and awareness of medication warning labeling. Even in this context it appears that a review of the Australian warning system would be useful particularly in the context of increasing evidence relating to associated driving risks. Reviewing text size and readability of messages including the addition of pictograms, as well as clarifying the importance of potential risk in a general community context, is recommended for consideration and further research.

[Clinical and behavioral approach]. / Approche clinique et comportementale.

During decades, the detection of alcohol related impairments was the main target for behavioral examination in drivers. The implementation of legislations on illegal drugs and driving, mainly cannabis, has led to an adaptation of the procedures by requiring, from the policemen, an evaluation of external signs of consumption, signs not anymore searched in case of alcohol. The current procedure in France consists in a medical evaluation by a required medical doctor, and based on the Field Sobriety test. This battery was nevertheless established for policemen and used by them in more than 40 countries. A present trend in the French authorities pushes to a back step to a chemical detection of drugs by policemen, by using saliva tests. This approach should have, in their opinion, the advantage of testing drivers without asking them to leave their car for an external evaluation. In our opinion, only a behavioral approach, could help the policemen to have at their disposal, relevant procedures for all situations, especially to face the increasing consumption of cannabis in drivers.

The role of captodiamine in the withdrawal from long-term benzodiazepine treatment.

BACKGROUND AND OBJECTIVES: Discontinuation of benzodiazepines can be associated with the emergence of a withdrawal syndrome which compromises successful termination of treatment. The objective of the present study was to evaluate whether a six week administration of captodiamine during benzodiazepine discontinuation could prevent emergence of a benzodiazepine withdrawal syndrome and thus facilitate discontinuation of these drugs. SUBJECTS AND METHODS: A controlled, randomised, double-blind trial of captodiamine versus placebo was conducted in 81 subjects presenting mild to moderate anxiety and treated for at least 6 months with a stable dose of benzodiazepine. Each subject was gradually weaned from benzodiazepines over a 14 day period using a tapering dose schedule and received captodiamine (150 mg/d) or placebo for 45 days from the beginning of the weaning period. OUTCOME MEASURES: The primary outcome criterion was the extent of withdrawal symptoms assessed using the Tyrer Benzodiazepine Withdrawal Symptom Questionnaire. Secondary outcome criteria were; self-evaluation of tension, anxiety, drowsiness and slowing of physical and mental performance using visual analogue scales; quality of sleep using the Spiegel questionnaire; anxiety using the Hamilton Anxiety Rating Scale; and cognitive function using a driving stimulation test. RESULTS: Analysis of the primary study criterion revealed a statistically significant difference (p < 0.0001) in the emergence of withdrawal symptoms between the two groups in favour of captodiamine at two, six and eight weeks following initiation of therapy. These results were supported by significant beneficial effects of captodiamine on the majority of secondary outcome measures. The switch to captodiamine was associated with an improvement in vigilance, which may be an advantage for the overall safety of the anxiolytic treatment, for example with regard to road safety. Discontinuation of captodiamine was not associated with the emergence of rebound anxiety. CONCLUSION: Captodiamine represents an interesting strategy for achieving benzodiazepine substitution with a low risk of dependence or impairment of cognitive function. Further clinical studies addressing the anxiolytic activity and safety of captodiamine in such subjects are merited.

Chromatographic determination of the association constant between 8-methoxypsoralen and modified beta-cyclodextrin: protective effect of hydroxypropyl-beta-cyclodextrin on 8-methoxypsoralen toxicity in human keratinocytes.

The retention of 8-methoxypsoralen (8-MOP) on an immobilised hydroxypropyl-beta-cyclodextrin (HP-beta-CD) column was analysed in HPLC by the determination of its Langmuir distribution isotherm. A such method was used to confirm the potential drug complexing role of this cyclodextrin. The 8-MOP/HP-beta-CD association constant (K) was equal to 29.5 and 18.7 M-1, respectively, at a temperature equal to 5 and 25 degrees C, respectively. These association constant values were used to determine the cytotoxicity profile of human keratinocyte cell line (HaCaT) in relation to the complex concentration. It was showed through these data that HP-beta-CD had a cytoprotective since a reverse effect of HP-beta-CD on 8-MOP cytotoxicity was observed.

Characterization of SRp46, a novel human SR splicing factor encoded by a PR264/SC35 retropseudogene.

The highly conserved SR family contains a growing number of phosphoproteins acting as both essential and alternative splicing factors. In this study, we have cloned human genomic and cDNA sequences encoding a novel SR protein designated SRp46. Nucleotide sequence analyses have revealed that the SRp46 gene corresponds to an expressed PR264/SC35 retropseudogene. As a result of mutations and amplifications, the SRp46 protein significantly differs from the PR264/SC35 factor, mainly at the level of its RS domain. Northern and Western blot analyses have established that SRp46 sequences are expressed at different levels in several human cell lines and normal tissues, as well as in simian cells. In contrast, sequences homologous to SRp46 are not present in mice. In vitro splicing studies indicate that the human SRp46 recombinant protein functions as an essential splicing factor in complementing a HeLa cell S100 extract deficient in SR proteins. In addition, complementation analyses performed with beta-globin or adenovirus E1A transcripts and different splicing-deficient extracts have revealed that SRp46 does not display the same activity as PR264/SC35. These results demonstrate, for the first time, that an SR splicing factor, which represents a novel member of the SR family, is encoded by a functional retropseudogene.

Characterization of multiple alternative RNAs resulting from antisense transcription of the PR264/SC35 splicing factor gene.

The PR264/SC35 splicing factor belongs to the family of SR proteins which function as essential and alternative splicing factors. Here, we report that the human PR264/SC35 locus is bidirectionally transcribed. Double in situ hybridization experiments have allowed simultaneous detection of sense and antisense RNA in human CCRF-CEM cells, suggesting that expression of the corresponding genes is not mutually exclusive. We have characterized three main classes of ET RNAs encoded by the opposite strand of the PR264/SC35 gene and containing PR264/SC35-overlapping sequences, PR264/SC35-non overlapping sequences or a combination of both. We show that their expression results from the use of alternative promoters, exons and polyadenylation signals. PR264/SC35-non overlapping ET mRNA species potentially encode two protein isoforms (449 and 397 amino acids) and are expressed from the PR264/SC35 promoting region. Northern blots and RNase protection analyses indicate that ET polyadenylated RNAs are differentially expressed in several human cell lines. Similar studies performed in the mouse have revealed that the bidirectional transcription of the PR264/SC35 locus is a conserved mechanism and that the open reading frame identified in a subset of human ET mRNAs is highly conserved (93% homology). Northern blot analyses performed with several murine tissues confirmed the differential expression of the ET gene and revealed that it is predominantly expressed in the testis.

Evaluation of alcohol consumption level in drivers when regranting licences after driving while intoxicated in France.

Biological markers form an important part of the decision-making process for regranting of driving licences in France. A major criterion in this respect is the need to distinguish between acute alcohol use and chronic abuse by applicants. Current markers reflect more hepatic damage than alcohol consumption and this stresses the need for more reliable markers.

RP 73870, a gastrin/cholecystokinin-B receptor antagonist with potent anti-ulcer activity in the rat.

RP 73870, the racemic potassium salt of (([N-(methoxy-3-phenyl)-N-(N-methyl-N-phenyl-carbamoylmethyl)- carbamoylmethyl]-3-ureido)-3-phenyl)-2-ethylsulfonate-(RS) is a potent, reversible antagonist of both gastrin and cholecystokinin-B receptors in guinea pig and rat tissues. This compound is a potent inhibitor of pentagastrin-stimulated gastric acid secretion in the perfused rat stomach. RP 73870 also inhibits basal gastric acid secretion in the rat, although at doses higher than that required for inhibition of pentagastrin-stimulated gastric acid secretion. RP 73870 is a potent inhibitor of aspirin-induced gastric damage in the rat. In the prevention of aspirin-induced gastric damage, RP 73870, given p.o., was 10-fold less potent than when given i.v. RP 73870 was as potent as a H2 receptor antagonist or proton pump inhibitor in the prevention of cysteamine-induced duodenal ulcers in the rat. Relative to other gastrin/cholecystokinin-B antagonists, RP 73870 demonstrates greater affinity to gastrin binding sites, and possesses a unique spectrum of in vivo biological activities appropriate for an anti-ulcer indication.

Pharmacological properties of ureido-acetamides, new potent and selective non-peptide CCKB/gastrin receptor antagonists.

We present here the pharmacological properties of 3 ureido-acetamide members of a novel family of non-peptide cholecystokinin-B (CCKB) receptor antagonists. RP 69758 (3-(3-[N-(N-methyl N-phenyl-carbamoylmethyl) N-phenyl-carbamoylmethyl] ureido)phenylacetic acid), RP 71483 ((E)-2-[3-(3-hydroxyiminomethyl phenyl) ureido] N-(8-quinolyl) N-[(1,2,3,4-tetrahydro 1-quinolyl)carbonylmethyl]acetamide) and RP 72540 ((RS)-2-[3-(3-[N-(3-methoxy phenyl) N-(N-methyl N-phenyl-carbamoylmethyl) carbamoylmethyl] ureido) phenyl] propionic acid) displayed nanomolar affinity for guinea-pig, rat and mouse CCKB receptors labelled with [3H]pCCK-8 or with the selective CCKB receptor ligand [3H]pBC264. RP 69758 and RP 72540 showed selectivity factors in express of 200 for CCKB versus CCKA receptors. All three compounds had also high affinity for gastrin binding sites in the stomach. The ureido-acetamides behaved as potent antagonists of CCK-8-induced neuronal firing in rat hippocampal slices in vitro, a functional model of brain CCKB receptor mediated responses. RP 69758 is also a potent gastrin receptor antagonist in vivo that dose dependently inhibits gastric acid secretion induced by i.v. injection of pentagastrin in the rat. None of the three ureido-acetamides, at concentrations up to 1 microM, significantly blocked CCK-8-evoked contractions of the guinea-pig ileum in vitro, a CCKA receptor bioassay. In ex vivo binding studies, i.p. administration of RP 69758 and RP 72540 resulted in a dose-dependent inhibition of [3H]pCCK-8 binding in mouse brain homogenate. However, the relative penetration of these ureido-acetamides into the forebrain after peripheral administration was below 0.01%. RP 71483 did not appear to cross the blood-brain barrier in quantities sufficient to prevent [3H]pCCK-8 binding at low doses, a property that makes it suitable for the exploration of the peripheral versus central origin of the behavioural effects observed following systemic administration of CCK. RP 69758, RP 71483 and RP 72540 are highly potent and selective non-peptide CCKB receptor antagonists which are useful tools to explore the physiological functions of CCKB receptors.

[Medication, narcotics and behavior at the wheel]. / Médicaments, drogues et comportement au volant.

Consumption of illicit drugs is generally underestimated as cause of road accidents. French legislation does not give the police authority to carry out their detection at once. If the regulation concerning driving and drinking is on the way of an hardening, a debate comes into being about the suppression of the penalization for consumption of some drugs whereas their involvement in road fatalities seems to be important. The influence of medicinal drugs on driver's behaviour forms the subject matter of many experimental studies, but the lack of a common methodology for testing their side effects prevents any possibility of categorization of the medicinal drugs depending of their risk for driving. This common methodology should include tests for the evaluation of risk taking and not only test for the detection of sedative effects. If self prescription and misuse of some medicinal drugs is often involved, if the prescription of some others should be allowed only for non drivers, it should be suitable to take into account the notions of therapeutical benefits and of preservation of social and professional integrity by the way of driving.

[Asthma and air pollution. A study of admissions to the Hospital of Saint-Nazaire]. / Asthme et pollution atmosphérique. Une étude des admissions à l'Hôpital de Saint-Nazaire.

To test the possible influence of atmospheric pollution on the frequency of asthmatic exacerbations we have looked to see whether there is a link between the number of daily admissions for asthma in hospitals in Saint-Nazaire and data from pollution sensors in the network of the Association for the Measurement of Atmospheric Pollution in the Loire estuary. The pollutions studied were sulphur dioxide, oxide of nitrogen (NOx) and non sedimenting dust (black smoke). The meteorological data (speed and direction of the wind and temperature) were also recorded. The study was carried out for 18 months in a retrospective fashion. During this period 372 hospital admissions were recorded in 229 subjects. The number of daily admissions correlated in a significant fashion with the level of black smoke (r = 0.149, p less than 0.001) and this result was particularly due to subjects who were less than 15 years old. In this group the frequency of hospital admission was doubled on those days when the level of smoke was at its most elevated. There was a weak link between the peaks of SO2 (r = 0.116, p less than 0.05). An analysis of the place of residence in those hospitals and the dominant direction of the wind did not enable us to confirm the role of the principal sources of industrial pollution, which were all situated to the east of Saint-Nazaire.

[Blood pressure response to antihypertension treatment. Comparison of data obtained at the doctor's office and by ambulatory blood pressure measurement]. / Réponse tensionnelle aux traitements antihypertenseurs. Confrontation des données obtenues en consultation et par mesure ambulatoire de la pression artérielle.

A comparative study of clinical and ambulatory responses to antihypertensive treatment was conducted retrospectively in 69 patients with mild to moderate arterial hypertension. The patients received different drugs, but blood pressure (BP) was measured by the same methods in each of them. (a) Clinical BP was measured with a mercury manometer some time after taking the last dose of antihypertensive drug: 24 hours in patients who took one daily dose, 12 hours in those who took two daily doses. (b) Ambulatory BP was measured with a Spacelabs SPM 5200 instrument over a minimum of 24 hours. The parameters compared were: (1) BP figures recorded. Correlation was very poor as regards both SBP (r = 0.42 before treatment, r = 0.55 after treatment) and DBP (r = 0.40 and r = 0.46 respectively). The mean BP value was lower in the ambulatory group than in the clinical group (-20/-12 mmHg), the difference being slightly less marked after treatment (-12/-6 mmHg). (2) Degree of absolute reduction of BP induced by treatment. Correlation was very poor between the two methods as regards both SBP (r = 0.46) and DBP (r = 0.49). (3) Proportion of responders and non-responders to treatment, the clinical response being defined as normalization and/or more than 10 p. 100 reduction of DBP, and the ambulatory response as a significant decrease of mean diastolic value over 24 hours. Among the 69 patients studied, there were 51 concordant cases (36 responders, 15 non-responders with the two methods) and 18 discordant cases (10 clinical responders but ambulatory non-responders, 8 clinical non-responders but ambulatory responders).(ABSTRACT TRUNCATED AT 250 WORDS)