Search results for " TOXICOLOGY AND PHARMACEUTICS"
showing 10 items of 461 documents
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…
In vivo release of non-neuronal acetylcholine from human skin by dermal microdialysis: Effects of sunlight, UV-A and tactile stimulus
2007
Non-neuronal acetylcholine (ACh) is expressed in epithelial, endothelial and immune cells. For example, the in vivo release of ACh from the human skin pretreated with botulinum toxin has recently been demonstrated. In the present experiments the effects of light (sunlight and solar radiation by a commercial UV-A applier) and of a tactile stimulus on the release of non-neuronal ACh were investigated. Release of ACh from the proximal and distal shin, i.e. anterior tibial region, was measured by dermal microdialysis in 20 min samples over a time period of at least 140 min. Control experiments were performed in a dark room throughout. In some experiments volunteers were exposed to sunshine (80-…
Increased acetylcholine levels in skin biopsies of patients with atopic dermatitis.
2003
Recent experimental evidence indicates that non-neuronal acetylcholine is involved in the regulation of basic cell functions. Here we investigated the cholinergic system in the skin of healthy volunteers and patients with atopic dermatitis (AD). The synthesizing enzyme, choline-acetyltransferase (ChAT), was studied by anti-ChAT immunohistochemistry and enzyme assay. Skin biopsies taken from healthy volunteers and from AD patients were separated into the 2 mm superfical (epidermis and upper dermis) and 3 mm underlying portion (deeper dermis and subcutis). ChAT enzyme activity was detected in homogenized skin and subcutaneous fat (about 13 nmol/mg protein/h). ChAT immunoreactivity was express…
Airway epithelial dysfunction and mesenchymal transition in chronic obstructive pulmonary disease: Role of Oct-4
2021
Abstract The airway epithelium is a dynamic tissue that undergoes slow but constant renewal. Dysregulation of airway epithelial function related to cigarette smoke exposure plays an important role in the pathophysiology of COPD. Oct4 is a transcription factor responsible for maintaining cellular self-renewal and regeneration, and CD146 and CD105/Endoglin are adhesion molecules involved in cell proliferation, differentiation, epithelial-mesenchymal-transition and tissue remodeling. Bronchial biopsy specimens (BBs) were obtained from 7 healthy controls (HC) and 10 COPD and subjected to paraffin embedding; BBs from HC were also used for epithelial cell expansion and pHBEC/ALI (air-liquid inter…
Interest of genotyping and phenotyping of drug-metabolizing enzymes for the interpretation of biological monitoring of exposure to styrene
2002
In the field of occupational and/or environmental toxicology, the measurement of specific metabolites in urine may serve to assess exposure to the parent compounds (biological monitoring of exposure). Styrene is one of the chemicals for which biological monitoring programs have been validated and implemented in environmental and occupational medicine. However, inter-individual differences in the urinary excretion exist both for the main end-products (mandelic acid and phenylglyoxylic acid) and for its specific mercapturic acids (phenylhydroxyethylmercapturic acids, PHEMA). This limits to a certain extent the use of these metabolites for an accurate assessment of styrene exposure. In a group…
Sporadic ALS is not associated with VAPB gene mutations in Southern Italy
2006
Abstract Mutations in the Cu/Zn superoxide dismutase (Sod1) gene have been reported to cause adult-onset autosomal dominant Amyotrophic Lateral Sclerosis (FALS). In sporadic cases (SALS) de novo mutations in the Sod1 gene have occasionally been observed. The recent finding of a mutation in the VAMP/synaptobrevin-associated membrane protein B (VAPB) gene as the cause of amyotrophic lateral sclerosis (ALS8), prompted us to investigate the entire coding region of this gene in SALS patients. One hundred twenty-five unrelated patients with adult-onset ALS and 150 healthy sex-age-matched subjects with the same genetic background were analyzed. Genetic analysis for all exons of the VAPB gene by DH…
Contractile responses of human thyroid arteries to vasopressin
2013
Abstract Aims In the present study we investigated the intervention of nitric oxide and prostacyclin in the responses to vasopressin of isolated thyroid arteries obtained from multi-organ donors. Main methods Paired artery rings from glandular branches of the superior thyroid artery, one normal and the other deendothelised, were mounted in organ baths for isometric recording of tension. Concentration–response curves to vasopressin were determined in the absence and in the presence of either the vasopressin V 1 receptor antagonist d(CH 2 ) 5 Tyr(Me)AVP (10 − 8 M), the nitric oxide synthase inhibitor N G -monomethyl- l -arginine ( L -NMMA, 10 − 4 M), or the inhibitor of prostaglandins indom…
Investigation into mechanisms mediating the inhibitory effect of 1,4-benzodiazepines on mast cells by gene expression profiling.
2013
Abstract Aims This study aims to identify by a molecular genetic approach potential targets in mast cells at which 1,4-benzodiazepines may cause their inhibitory effect on mast cell activity. Main methods Gene expression analyses with microarray gene chip and/or quantitative PCR were performed using 1,4-benzodiazepine-treated human mast cell leukemia HMC-1.2 cells, promyelocytic leukemia HL-60 cells and human mast cells from healthy volunteers and patients with mast cell activation disease (MCAD). Pathway analysis was applied to search for enriched biological functions and canonical pathways within differentially regulated genes. Key findings Both neoplastic and normal human mast cells expr…
Blockade of nicotinic and muscarinic receptors facilitates spontaneous migration of human peripheral granulocytes: failure in cystic fibrosis.
2012
Circulating leucocytes express muscarinic (m) and nicotinic (n) receptors and synthesize acetylcholine (ACh) regulating various cell functions. Leucocytes from patients with cystic fibrosis contain less ACh; therefore it was tested whether the regulation of cellular functions like migration differed from healthy volunteers.Peripheral blood (10-20 ml) was used, leucocytes were isolated by Ficoll® gradient and the commercial MIGRATEST® combined with flow cytometric analysis was applied (pore size 3 μm).In the absence of test substances 4900±1800 (n=10) leucocytes migrated within a time period of 2 h. In the presence of tubocurarine (TC, 30 μM) the cell number increased to 7500±2700 [n=10] cor…
Dysfunction of the non-neuronal cholinergic system in the airways and blood cells of patients with cystic fibrosis.
2007
Abstract The non-neuronal cholinergic system is widely expressed in human airways, skin and immune cells. Choline acetyltransferase (ChAT), acetylcholine and nicotine/muscarine receptors are demonstrated in epithelial surface cells, submucosal glands, airway smooth muscle fibres and immune cells. Moreover, acetylcholine is involved in the regulation of cell functions like proliferation, differentiation, migration, organization of the cytoskeleton, cell–cell contact, secretion and transport of ions and water. Cystic fibrosis (CF), the most frequent genetic disorder, is known to be caused by a mutation of the CF-gene coding for the cystic fibrosis transmembrane regulator protein (CFTR). CFTR …