An open randomized multicentre Phase 2 trial to assess the safety of DAV132 and its efficacy to protect gut microbiota diversity in hospitalized patients treated with fluoroquinolones.

Background: DAV132 (colon-targeted adsorbent) has prevented antibiotic-induced effects on microbiota in healthy volunteers.

Objectives: To assess DAV132 safety and biological efficacy in patients.

Patients And Methods: An open-label, randomized [stratification: fluoroquinolone (FQ) indication] multicentre trial comparing DAV132 (7.

A Colon-Targeted Adsorbent (DAV132) Does Not Affect the Pharmacokinetics of Warfarin or Clonazepam in Healthy Subjects.

DAV132 is a novel colon-targeted adsorbent that prevents the deleterious impact of antibiotics on gut microbiota without modifying their systemic availability. A randomized, Latin-square crossover, open-label trial with 2 substudies in 18 and 24 healthy volunteers evaluated the pharmacokinetic (PK) bioequivalence of warfarin, a drug with a narrow therapeutic index (NTI), and clonazepam, both widely used for the treatment of chronic conditions, with or without coadministration of DAV132 7.5 g.

Protection of the Human Gut Microbiome From Antibiotics.

Background: Antibiotics are life-saving drugs but severely affect the gut microbiome with short-term consequences including diarrhea and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers.

The outcome of fistulotomy for anal fistula at 1 year: a prospective multicentre French study.

Aim: The study aimed to evaluate outcome at 1 year of one- and two-stage fistulotomy for anal fistula in a large group of patients.

Method: A prospective multicentre observational study was designed to include patients with anal fistula treated by one- or two-stage fistulotomy. Data were collected using a self-administered questionnaire before surgery, during healing and at 1 year after surgery.

One-year outcome of haemorrhoidectomy: a prospective multicentre French study.

Aim: An evaluation was performed of the 1-year outcome of open haemorrhoidectomy (Milligan and Morgan alone or with posterior mucosal anoplasty [the Leopold Bellan procedure]).

Method: A prospective, multicentre, observational study included all patients having a planned haemorrhoidectomy from January 2007 to June 2008. Data were collected before surgery, and at 3 months and 1 year after surgery.

Sphincter-sparing anal-fissure surgery: a 1-year prospective, observational, multicentre study of fissurectomy with anoplasty.

Aim: Internal sphincterotomy is the standard surgical treatment for chronic anal fissure, but is frequently complicated by anal incontinence. Fissurectomy is proposed as an alternative technique to avoid sphincter injury. We describe 1-year outcomes of fissurectomy.

Adherence to treatment and quality of life during hepatitis C therapy: a prospective, real-life, observational study.

Background: Adherence is important for therapy of chronic diseases, but has still not been well studied in real life in chronic hepatitis C.

Aims: To assess adherence to hepatitis C combination therapy in routine clinical practice and to identify factors associated with imperfect adherence.

Methods: This cohort study included unselected chronic hepatitis C patients initiating peginterferon α-2b plus ribavirin.

Maintenance therapy and 3-year outcome of opioid-dependent prisoners: a prospective study in France (2003-06).

Aims: To describe the profile of imprisoned opioid-dependent patients, prescriptions of maintenance therapy at imprisonment and 3-year outcome in terms of re-incarceration and mortality.

Design: Prospective, observational study (France, 2003-06).

Setting: Health units of 47 remand prisons.

Patient education improves adherence to peg-interferon and ribavirin in chronic genotype 2 or 3 hepatitis C virus infection: a prospective, real-life, observational study.

Aim: To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response (SVR) in a real-life setting in genotype 2/3 hepatitis C, as there are few adherence data in genotype 2/3 infection, even from randomized trials.

Methods: This prospective survey included genotype 2/3 patients who received peg-interferon alfa-2b and ribavirin. There was no intervention.

Multicentre study of hepatitis B virus genotypes in France: correlation with liver fibrosis and hepatitis B e antigen status.

The clinical significance of hepatitis B virus (HBV) genotypes is still under debate. The aims of this study were to assess the distribution of HBV genotypes in France and to identify the associations between HBV genotypes and patient demographics, severity of liver disease and HBeAg status in patients referred to tertiary care centres. This was a French, multicentre, retrospective study on 262 patients with chronic HBV infection.

Hepatitis B virus genotypes and extrahepatic manifestations.

Background/aims: This study aimed at correlating the presence of extrahepatic manifestations with hepatitis B virus (HBV) genotypes in patients with chronic HBV infection.

Methods: This was a national (France), multicenter, retrospective, cross-sectional study. HBV genotypes were determined in 190 patients HBsAg-positive for at least 6 months and documented before any treatment.

Chronic MPTP treatment reproduces in baboons the differential vulnerability of mesencephalic dopaminergic neurons observed in Parkinson's disease.

Chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to baboons was shown previously to result in a motor syndrome and a pattern of striatal dopaminergic fibre loss similar to those observed in idiopathic Parkinson's disease. In the present study, tyrosine hydroxylase-immunoreactive neurons were quantified in the mesencephalon of control (n = 4) and chronically MPTP-treated (n = 3) baboons. MPTP induced a significant reduction in neuronal cell density in the substantia nigra (63.

In vivo high intrinsic efficacy of triazolam: a positron emission tomography study in nonhuman primates.

The triazolobenzodiazepine triazolam is a central-type benzodiazepine receptor (BZR) ligand that is widely prescribed as a hypnotic agent. Triazolam produces its effects through potentiation of gamma-aminobutyric acid-mediated neurotransmission. Findings reported from in vitro binding studies showed some discrepancies concerning the pharmacological characteristics of triazolam.

Synthesis of 3-[18F]fluoromethyl-BTCP and evaluation as a potential PET radioligand for the dopamine transporter in baboons.

In an attempt to visualize in vivo the dopamine transporter and evaluate its potential as an imaging tool for monitoring dopamine fiber degeneration by positron emission tomography, the 18F-positron-emitting analogue of 3-fluoromethyl-1-[1-(2-benzothienyl)-cyclohexyl]-piperidine, [18F]BTCP, was synthesized and tested in a primate model of hemiparkinsonism. [18F]BTCP was obtained from cyclotron-produced n.c.

Modeling analysis of [11C]flumazenil kinetics studied by PET: application to a critical study of the equilibrium approaches.

The multi-injection modeling approach was used for the in vivo quantitation of benzodiazepine receptors in baboon brain using positron emission tomography (PET) and [11C]flumazenil (RO 15-1788) as a specific ligand. The model included three compartments (plasma, free, and bound ligand) and five parameters (including the benzodiazepine receptor concentration). The plasma concentration after correction for the metabolites was used as the input function.

Stable parkinsonian syndrome and uneven loss of striatal dopamine fibres following chronic MPTP administration in baboons.

The progressive degeneration of dopamine neurons observed in idiopathic Parkinson's disease was mimicked by injecting low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to baboons, on a chronic basis. Five Papio papio baboons were treated on two different regimens (chronic intravenous administration at weekly intervals for 20-21 months or, daily MPTP treatment for five days followed five to six months later by chronic weekly injections for 5-21.5 months).

In vivo visualization of central muscarinic receptors using [11C]quinuclidinyl benzilate and positron emission tomography in baboons.

The muscarinic antagonist, quinuclidinyl benzilate (QNB), labeled with carbon 11 was used as a radioligand to visualize in vivo by positron emission tomography (PET) the central muscarinic acetylcholine receptors (mAChR) in baboons (Papio papio). The binding characteristics of [11C]QNB showed its specific binding to central mAChR. [11C]QNB brain uptake was high in cerebral cortex and striatum, areas that are rich in mAChR, whereas it decreased rapidly in cerebellum, evidencing non-specific binding in this structure that is almost devoid of mAChR.