Prevalence and clinical features of opioid-induced constipation in the general population: A French study of 15,000 individuals.

BACKGROUND: Constipation is common during opioid therapy and can compromise analgesia. AIM: The aim of this article is to determine the prevalence and clinical characteristics of opioid-induced constipation (OIC) in France. METHODS: A questionnaire study was conducted in a representative sample of the French general population. Participants completed a 31-item questionnaire covering opioid use during the previous six months, and the occurrence of constipation (defined as <3 bowel movements per week, straining during defaecation, or both) during opioid treatment. RESULTS: Data were obtained from 15,213 participants, of whom 4753 (31.2%) reported opioid use. Most analgesics (96.5%) were classified as World Health Organization step II analgesics, and the remainder were step III. The most common indications for opioids were bone or joint pain, and soft tissue pain. Overall, 414/4753 (8.7%) opioid users reported OIC while the prevalence of OIC reached 21% in case of regular or prolonged (>1 month) opioid use. Other characteristics associated with OIC included female gender, age ≥50 years and use of step III opioids. Only 177/414 (42.8%) participants with OIC had used medications (most commonly osmotic laxatives) to treat constipation, and satisfaction with constipation medication was moderate (mean (SD) score 7.2 (1.3) on a scale of 0-10). CONCLUSIONS: Approximately one-third of a representative French population had used opioids within the previous six months, and 9% of users had experienced OIC, which is more frequent in case of regular use. OIC appears to be under-treated, and participants' satisfaction with their constipation medications was only moderate, suggesting that significant unmet need remains in OIC management.

Comparison of milk fatty acid profiles measured on Kouri cows near Lake Chad and on dairy cattle as reported by meta-analytical data.

Kouri (Bos taurus) is a breed aboriginal from Lake Chad and threatened with extinction. This study aimed to compare milk fatty acid profiles measured on Kouri cows and on high-yielding dairy cattle in Europe and elsewhere as reported by meta-analytical data (22 experimentations). Milk samples were collected from 14 Kouri dairy cows in dry season (March to June) and fatty acids (FA) were determined by gas chromatography. Overall, 32 FA have been identified. Kouri showed lower values (P < 0.001) in the sum of saturated FA (SFA, -10.9 pts), cis-9, cis-12 18:2 (-1.00 pt) (P < 0.01, higher values (P < 0.001) in the sum of monounsaturated FA (MUFA, +15.3 pts), C18:0) (+3.5 pts), cis-9, trans-11 C18:2-CLA (+1.00 pts), trans-11 18:1 (+1.4 pts) and (P < 0.01) in cis-9, C18:1 (+3.00 pts) acids. The differences between the milk FA profile of the Kouri cows and that obtained from meta-analytical data could be the possible consequence of the use of particular lake pastures by Kouri cows.

[Risk factors of upper gastrointestinal complications in outpatients on antiplatelet therapy: description and management]. / Facteurs de risque de complications digestives des patients sous antiagrégant plaquettaire suivis en cardiologie de ville : description et prise en charge.

OBJECTIVES: Patients on antiplatelet therapy have a gastrointestinal bleeding risk. It is increased by risk factors. The frequency of those risk factors, the prevalence of upper digestive symptoms and their management in patients on antiplatelet agents is unknown. PATIENTS AND METHODS: We performed an observational multi-centred prospective survey among 560 French cardiologists with private practice. Each cardiologist completed a questionnaire for the first four patients treated with antiplatelet agents in primary or secondary prevention. RESULTS: Among the 2182 patients included, (age = 67 ± 11 years; 74% male), 83% had at least one gastrointestinal bleeding risk factor and 38.9% had a history of upper digestive tract symptom. A history of gastrointestinal bleeding was reported in 3.4% and a history of documented gastro-duodenal ulcer in 5.5%. A proton pump inhibitor was already prescribed in 39% of the patients. At the time of the consultation, upper digestive symptoms were described in 21% of the patients. In those patients with symptoms, 85% had no modification in antiplatelet therapy and 62.7% were prescribed gastro-protective drugs (proton pump inhibitors: 51.8%, H(2)-blockers 3.6% other anti-acid medication: 7.3%). CONCLUSION: Among patients on antiplatelet agents, the prevalence of upper digestive symptoms and risk factors for gastrointestinal bleeding is high. Preventative management needs to be clarified in this population.

[Adenoviruses structure]. / Structure des ad�novirus.

Adenoviruses are double stranded DNA non enveloped viruses. Although these viruses are widely studied for gene therapy and anticancer applications, fundamental knowledge of these viruses, especially from a structural point of view is lacking. This is probably partly responsible for the limited success of the first clinical trials.With these viruses, one of the main conditions necessary to use adenoviruses for therapeutic application is structural modification of the virus. Indeed, one has to retarget the virus to specific tissues and/or remove all the immunogenic loops present on the outside of the virus in order to limit the host immune response. To make these changes rationally, the structure of the capsid has to be known at atomic resolution. Today, electron microscopy is the only tool that enables us to have access to the structure of the entire virus, but only at intermediate resolution. Because the atomic structures of the adenovirus major capsid proteins are known, one can combine these structures with the electron microscopy based envelope to calculate a model of the capsid at quasi-atomic resolution. These kinds of models are useful to visualize and understand the complexity of the virus. Nevertheless, the structure of the entire capsid at atomic resolution will really be necessary to use the virus in a safe way.

Structure of the dodecahedral penton particle from human adenovirus type 3.

The sub-viral dodecahedral particle of human adenovirus type 3, composed of the viral penton base and fiber proteins, shares an important characteristic of the entire virus: it can attach to cells and penetrate them. Structure determination of the fiberless dodecahedron by cryo-electron microscopy to 9 Angstroms resolution reveals tightly bound pentamer subunits, with only minimal interfaces between penton bases stabilizing the fragile dodecahedron. The internal cavity of the dodecahedron is approximately 80 Angstroms in diameter, and the interior surface is accessible to solvent through perforations of approximately 20 Angstroms diameter between the pentamer towers. We observe weak density beneath pentamers that we attribute to a penton base peptide including residues 38-48. The intact amino-terminal domain appears to interfere with pentamer-pentamer interactions and its absence by mutation or proteolysis is essential for dodecamer assembly. Differences between the 9 Angstroms dodecahedron structure and the adenovirus serotype 2 (Ad2) crystallographic model correlate closely with differences in sequence. The 3D structure of the dodecahedron including fibers at 16 Angstroms resolution reveals extra density on the top of the penton base that can be attributed to the fiber N terminus. The fiber itself exhibits striations that correlate with features of the atomic structure of the partial Ad2 fiber and that represent a repeat motif present in the amino acid sequence. These new observations offer important insights into particle assembly and stability, as well as the practicality of using the dodecahedron in targeted drug delivery. The structural work provides a sound basis for manipulating the properties of this particle and thereby enhancing its value for such therapeutic use.

Deciphering Arabidopsis thaliana gene neighborhoods through bibliographic co-citations.

In the framework of genome annotation, scientific literature is obviously the major source of biological knowledge. The aim of the work described in this paper is to exploit this source of data for the model plant Arabidopsis thaliana. The first step has consisted in constituting a relevant bibliographic references dataset for plant genomic research. Genes co-citations have then been systematically annotated in this reference dataset, starting from the simple idea that if genes are cited in the same publication, they must probably share some related functional properties. In order to deal with the synonymous gene name problem, a gene name reference list has been constituted starting from A. thaliana SwissProt entries. This list was used to build clusters of co-cited genes by a single linkage procedure such that any gene in a given cluster possesses at least one co-cited partner in the same cluster. Analysis of the clusters demonstrate the biological consistency of this approach, with only very few fortuitous links. As an example, a cluster including genes related to flowering time is more deeply described in the paper. Finally, a graphical representation of each cluster was performed, which provides a convenient way to retrieve the genes (the nodes of the graphs) and the references in which they were co-cited (the edges of the graphs). All the results can be accessed at the URL http://chlora.Igi.infobiogen.fr:1234/bib_arath/.

Beraprost sodium-fluindione combination in healthy subjects: pharmacokinetic and pharmacodynamic aspects.

Beraprost sodium (BPS), an orally active PGI2 (prostaglandine 12) analogue possesses vasodilatating and platelet aggregation inhibiting properties. It is being developed in peripheral arterial occlusive disease. As in future clinical practice BPS might be co-prescribed with oral anticoagulants, we investigated its interaction with fluindione, a vitamin K antagonist in healthy subjects in a randomised, double-blind, placebo-controlled, crossover study. Twelve healthy Caucasian male subjects randomly received BPS 40 microg t.i.d. or placebo for 3 days. There was a 7 day wash out between the two treatment periods. On day 3 of each treatment, the subjects ingested concomitantly a single oral dose of 20 mg of fluindione. The main assessment criterion was fluindione's pharmacokinetics. Secondarily, pharmacodynamic measurements of coagulation (prothrombin time, and International Normalised Ratio, INR) and platelet function (in vitro closure time assessed by PFA-100) were performed. Fluindione was assayed by HPLC with UV detection up to 96 h post-drug. No statistical difference could be evidenced on any fluindione pharmacokinetic parameters between BPS and placebo phases: t 1/2 (h): 35.9 (8.2) vs. 34.0 (4.2) [90% CI 105.8 (95.5-116.2)]; T(max) (h): 2.0 (0.5-6.0) vs. 4.0 (0.5-6.0) [90% CI 136.4 (70.7-208.9)]; Cmax (mg/L): 3.1 (0.6) vs. 2.9 (0.5) [90% CI 94.1 (85.8-103.2)]; AUC 0-inf (mg/h/L): 117.0 (31.5) vs. 113.9 (33.8) [90% CI 97.6 (87.5-108.8)]. The studied doses of BPS did not affect platelet function, at least as assessed by the in vitro platelet function testing. Twenty milligrams of fluindione marginally modified the PT ratio and INR, however, no statistically significant difference was found between BPS and placebo phases. In conclusion, a 3 day regimen of BPS 40 microg t.i.d. by oral route does not seem to affect pharmacokinetic parameters of a fluindione 20 mg single dose.