Search results for "45"
showing 10 items of 1896 documents
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…
Evaluation of DNA ploidy and degree of DNA abnormality in benign and malignant melanocytic lesions of the skin using video imaging.
2000
BACKGROUND Making a morphologic distinction between benign and malignant melanocytic tumors of the skin is frequently difficult, especially because “gray zones” between these lesions often exist. DNA image cytometry as an adjuvant method for the diagnosis and prognostic prediction of premalignant lesions and malignant tumors of many other organs is already well established. The aim of this study was to determine whether DNA image cytometry is helpful in distinguishing benign from malignant melanocytic lesions and whether cytometry would give valid information with which to predict the prognoses associated with malignant melanomas. METHODS DNA image cytometry was performed on 127 benign and …
Cytochrome P450 2E1 variable number tandem repeat polymorphisms and health risks: A genotype-phenotype study in cancers associated with drinking and/…
2012
Cytochrome P450 2E1 (CYP2E1) is one of the main enzymes involved in the oxidation of ethanol and in the transformation of a number of potentially dangerous compounds. It has various polymorphic sites, one of which is a variable number tandem repeat (VNTR) polymorphism previously described in the 5'-flanking region. The aim of this study was to investigate the genotype-phenotype association between CYP2E1 VNTR polymorphisms and risky health habits in healthy subjects and to analyze the associations between these polymorphisms with drinking- and/or smoking-related cancers. We analyzed 166 healthy subjects by genotyping for the CYP2E1 VNTR polymorphism associated with drinking and/or smoking h…
Neddylation inhibition ameliorates steatosis in NAFLD by boosting hepatic fatty acid oxidation via the DEPTOR-mTOR axis
2021
Objective Neddylation is a druggable and reversible ubiquitin-like post-translational modification upregulated in many diseases, including liver fibrosis, hepatocellular carcinoma, and more recently, non-alcoholic fatty liver disease (NAFLD). Herein, we propose to address the effects of neddylation inhibition and the underlying mechanisms in pre-clinical models of NAFLD. Methods Hepatic neddylation measured by immunohistochemical analysis and NEDD8 serum levels measured by ELISA assay were evaluated in NAFLD clinical and pre-clinical samples. The effects of neddylation inhibition by using a pharmacological small inhibitor, MLN4924, or molecular approaches were assessed in isolated mouse hep…
Acute Effects of High-intensity Resistance Exercise on Cognitive Function
2021
The purpose of the present study was to examine the influence of an acute bout of high-intensity resistance exercise on measures of cognitive function. Ten men (Mean ± SD: age = 24.4 ± 3.2 yrs; body mass = 85.7 ± 11.8 kg; height = 1.78 ± 0.08 m; 1 repetition maximum (1RM) = 139.0 ± 24.1 kg) gave informed consent and performed a high-intensity 6 sets of 10 repetitions of barbell back squat exercise at 80% 1RM with 2 minutes rest between sets. The Automated Neuropsychological Assessment Metrics (ANAM) was completed to assess various cognitive domains during the familiarization period, immediately before, and immediately after the high-intensity resistance exercise bout. The repeated measures …
Cytochrome P450 regulation by hepatocyte nuclear factor 4 in human hepatocytes: A study using adenovirus-mediated antisense targeting
2001
Abstract Hepatocyte nuclear factor 4 (HNF4) is a member of the nuclear receptor super-family that has shown activating effects on particular cytochrome P450 (CYP) promoters from several species. However, its role in the regulation of human CYPs in the liver is still poorly understood, as no comprehensive studies in human-relevant models have been performed. In the present study, we have investigated whether HNF4 plays a general role in the expression of 7 major CYP genes in primary cultured human hepatocytes. To this end, we developed an adenoviral vector for efficient expression of HNF4 antisense RNA. Transduction of human hepatocytes with the recombinant adenovirus resulted in a time-depe…
Attitude and knowledge of pain management among Italian nurses in hospital settings
2015
Pain is multidimensional, and, as such, the chief reason patients seek urgent healthcare services. If inadequately assessed and untreated, pain may negatively impact on the quality of life of the patient. Treating pain is an important step in regaining control over quality of life. The objective of the present study is to examine the level of knowledge and types of approach among Italian nurses who deal with pain assessment and management. The Ferrell and McCaffery's Knowledge and Attitudes Survey Regarding Pain (KASRP) was distributed to 286 nurses employed in one of the biggest specialized hospitals in Rome, Italy. The interviewed staff work at three different settings, according to the h…
Usefulness of echocardiography in the assessment of internal medicine inpatients: An analysis according to ACC/AHA guidelines
1999
BACKGROUND: We aimed to analyze the importance of echocardiography in our Internal Medicine Institute. We think that this technique could have a large impact in the evaluation of the internistic inpatient who is usually affected by multiple pathological problems. METHODS: Analysis was performed according to the ACC/AHA guidelines for the application of echocardiography. The data of 1211 consecutive inpatients were analyzed. RESULTS: Sixty-three per cent of all the patients had two or more associated diseases. Moreover, patients in whom echocardiography could be considered appropriate or useful were 67%. Our results point out that echocardiographic examination is generally a technique of gre…