Search results for "digestive system"
showing 10 items of 1747 documents
Biomechanical properties of oesophagus wall under loading
2003
In this investigation, firstly, the biomechanical properties of different parts of oesophagus were determined. Oesophagus stress and strain are the greatest in the cervical part for all age groups. The human oesophagus deforms unevenly, depending on the direction of load in relation to the organ's axis, it exhibits anisotropical behaviour. With the age the values of mechanical parameters of the oesophagus wall reduce, in particular beginning from 45 years of age, but the modulus of elasticity increases. Biomechanical properties of the oesophagus depend on the architecture of its structure. By loading the organ in the circumferential direction, microfibrilae rupture and deformation of the mu…
Risk factors for recurrence and incontinence after anal fistula surgery
2009
Objective: Fistula-in-ano continues to raise problems that require important therapeutic decisions. Our aim was to evaluate its recurrence and incontinence risk factors. Method: We analysed a series of 279 patients who had undergone anal fistula surgery with long-term follow-up. Results: 42.7% of the fistulae were considered complex and 46% had been referred from other institutions. There was delayed healing or recurrence in 7.2% patients, which appeared at a median of 4 months. The factors associated with recurrence were the type of fistula (extrasphincteric/suprasphincteric), nonidentification of internal opening (IO), recurrent or complex fistulae (CF), and associated chronic abscess. On…
Overcoming a “Probable” Diagnosis in Antimitochondrial Antibody Negative Primary Biliary Cirrhosis: Study of 100 Sera and Review of the Literature
2010
Serum anti-mitochondrial antibodies (AMA) are the serological hallmark of primary biliary cirrhosis (PBC), yet up to 15% of PBC sera are AMA negative at routine indirect immunofluorescence (IIF) while being referred to as “probable” cases. The diagnostic role of PBC-specific antinuclear antibodies (ANA) remains to be determined. We will report herein data on the accuracy of new laboratory tools for AMA and PBC-specific ANA in a large series of PBC sera that were AMA-negative at IIF. We will also provide a discussion of the history and current status of AMA detection methods. We included IIF AMA-negative PBC sera (n = 100) and sera from patients with other chronic liver diseases (n = 104) th…
Cytochrome P-450 mRNA expression in human liver and its relationship with enzyme activity.
2001
CYP activity and protein contents have been measured in human liver using different techniques. In contrast, CYP mRNA data are scarce and the relationships between CYP mRNA contents and activities have not been established. These studies deserve further attention because mRNA determinations by RT-PCR require a very small amount of material (e.g., liver needle biopsy) and could provide important data regarding CYP expression regulation. In this study we measured in 12 human liver samples the mRNA contents of 10 CYPs by quantitative RT-PCR and the metabolic activities using specific substrates. mRNA contents and activities showed high correlation coefficients for CYP1A1, CYP1A2, CYP3A4, CYP2D…
Serum levels of aripiprazole and dehydroaripiprazole, clinical response and side effects
2007
Aripiprazole, a novel antipsychotic drug, is metabolized by CYP3A4 and CYP2D6 forming mainly its active metabolite dehydroaripiprazole. In this study, aripiprazole and dehydroaripiprazole serum levels of psychiatric patients were measured and related to dose, comedication, and clinical effects including therapeutic and side effects. Patients were treated with mean doses of 20 +/- 8 mg/day of aripiprazole (median 15 mg, range 7.5-60 mg). Serum levels correlated significantly with the dose (r = 0.419; P0.01), with a mean value of aripiprazole of 214 +/- 140 ng/ml. Mean concentrations of the active metabolite dehydroaripiprazole amounted to 40% of the parent compound. Comedication with CYP3A4 …
Rapid and reliable genotyping procedure for detection of alleles with mutations, deletion, or/and duplication of the CYP2D6 gene
2009
Abstract Background Polymorphisms of cytochrome P450 2D6 (CYP2D6) have a significant effect on the pharmacokinetics of most tricyclic antidepressants. More than 150 alleles lead to four distinct phenotypes of drug metabolism. The phenotypes are described as ultrarapid, extensive, intermediate, and poor metabolizers. Therapeutic plasma levels of CYP2D6 substrates may be difficult to achieve. Here we describe a rapid and reliable procedure for CYP2D6*4, *3, *6, and *9 genotyping. Design and methods Serum concentrations of venlafaxine and its pharmacologically active metabolite, O-desmethylvenlafaxine, were measured in patients treated with the antidepressant venlafaxine, a substrate of CYP2D6…
The role of cytochrome P450 2D6 in the metabolism of moclobemide.
1996
The metabolic fate of moclobemide (Ro 11-1163), a new reversible and selective inhibitor of monoamine oxidase type A (MAO-A), has been assessed in a pilot study in 2 debrisoquine poor metabolizers (PM) and 4 extensive metabolizers (EM) after multiple oral dosings of moclobemide with and without co-medication of dextromethorphan. Absorption and disposition parameters were not different between PM and EM. Concurrent application of dextromethorphan, a selective substrate of CYP2D6, did not affect the pharmacokinetics of moclobemide. These results indicate that the cytochromal isoenzyme CYP2D6 does not play a major role in the metabolic degradation of moclobemide. Limited CYP2D6 activities beca…
CYP2D6 genotype and phenotyping by determination of dextromethorphan and metabolites in serum of healthy controls and of patients under psychotropic …
1998
Fourteen drug free healthy volunteers and 22 psychiatric patients under psychotropic medication were phenotyped for their individual CYP2D6 activity using dextromethorphan as a probe drug. A solution containing 20 mg dextromethorphan was administered and blood was taken 60 min later for determination of dextromethorphan and metabolites in serum. For comparison, urine was collected over 8 h after ingestion of 20 mg dextromethorphan in a separate test. The CYP2D6 phenotype was determined from the ratio of dextromethorphan to dextrorphan. For genotyping, mutant alleles of the CYP2D6 gene were identified using allele-specific polymerase chain reactions. Genotyping revealed five poor metabolizer…
Trends for genetic variation of Hepatitis C Virus quasispecies in Human Immunodeficiency virus-1 coinfected patients
2007
Chronic infection by Hepatitis C Virus (HCV) causes liver fibrosis, which is accelerated by unknown mechanisms in patients with HIV-1 coinfection. The evolution of HCV quasispecies in this setting of coinfection is not fully understood. To compare HCV quasispecies between HIV-HCV coinfection and HCV monoinfection, we sequenced 340 HCV clones from the HVR-1 and NS3 regions at two different time points in two groups of treatment-naive patients with HCV-1a infection: (1) HIV-HCV positive (n=6); and (2) HIV negative-HCV positive (n=3). In HCV/HIV coinfection, we found a trend for reduced HCV genetic complexity and diversity, and a trend towards reduced dN/dS ratios in the HVR-1 region, especial…
Extent and patterns of MGMT promoter methylation in glioblastoma- and respective glioblastoma-derived spheres.
2010
Abstract Purpose: Quantitative methylation-specific tests suggest that not all cells in a glioblastoma with detectable promoter methylation of the O6-methylguanine DNA methyltransferase (MGMT) gene carry a methylated MGMT allele. This observation may indicate cell subpopulations with distinct MGMT status, raising the question of the clinically relevant cutoff of MGMT methylation therapy. Epigenetic silencing of the MGMT gene by promoter methylation blunts repair of O6-methyl guanine and has been shown to be a predictive factor for benefit from alkylating agent therapy in glioblastoma. Experimental Design: Ten paired samples of glioblastoma and respective glioblastoma-derived spheres (GS), c…