ABSTRACT
Pesticides have been suspected to act as endocrine disruptive compounds (EDCs) through several mechanisms of action, however data are still needed for a number of currently used pesticides. In the present study, 30 environmental pesticides selected from different chemical classes (azole, carbamate, dicarboximide, organochlorine, organophosphorus, oxadiazole, phenylureas, pyrazole, pyrimidine, pyrethroid and sulfonylureas) were tested for their ability to alter in vitro the transcriptional activity of the androgen receptor in the MDA-kb2 reporter cell line. The responsiveness of the system was checked by using a panel of reference ligands of androgen and glucocorticoid receptors. When tested alone at concentrations up to 10 µM, none of the studied pesticides were able to induce the reporter gene after a 18 h exposure. Conversely, co-exposure experiments with 0.1 nM dihydrotestosterone (DHT) allowed identifying 15 active pesticides with IC(50) ranging from 0.2 µM for vinclozolin to 12 µM for fenarimol. Fipronil and bupirimate were here newly described for their AR antagonistic activity.
Subject(s)
Androgen Receptor Antagonists/toxicity , Endocrine Disruptors/toxicity , Pesticides/toxicity , Androgen Receptor Antagonists/administration & dosage , Cell Line, Tumor , Dihydrotestosterone/toxicity , Endocrine Disruptors/administration & dosage , Genes, Reporter/drug effects , Humans , Inhibitory Concentration 50 , Time Factors , Transcription, Genetic/drug effectsABSTRACT
UNLABELLED: The aim of the study was to determine what is the correlation between immunological phenomena and pathological changes in chronic gastritis and how it refers to the histology and endoscopy. PATIENTS AND METHODS: 42 patients with dyspepsia underwent following procedure: 1) gastroscopy and antral biopsy of 3 specimens; 2) histology; 3) immunofluorescence of the specimens in purpose to detect bound immunoglobulins using antibodies anti-human IgA + IgG + IgM labelled with rhodamine; 4) serologic test for anti-H.pylori antibodies. The research included 17 females and 25 males (ages 30-86, median 53.4 +/- 15.47). The obtained data were compared referring to mutual correlations and presented according to the kind of pathological changes depending on:--presence or absence of Helicobacter pylori infection;--presence or absence of anti-Helicobacter pylori antibodies;--presence or absence of lymphocytic infiltration;--presence or absence of bound immunoglobulins in gastric mucosa. RESULTS: --We have not observed ulcerations in anti-Helicobacter pylori seronegative group;--intestinal metaplasia and gastric ulcer were more frequent in bound immunoglobulins positive group;--biliary reflux was observed less frequently in lymphocyte infiltration negative group then in the positive one. CONCLUSION: pathological changes in chronic gastritis may depend not only on the presence of Helicobacter pylori infection, but also on the presence and quality of immunological response on its antigens.
Subject(s)
Gastric Mucosa/pathology , Gastritis/immunology , Helicobacter Infections/immunology , Helicobacter pylori/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Bacterial/immunology , Biopsy , Chronic Disease , Female , Fluorescent Antibody Technique , Gastritis/microbiology , Gastritis/pathology , Gastroscopy , Helicobacter Infections/pathology , Humans , Male , Middle AgedABSTRACT
Replacement of the carboxyl group of 2-(3-benzoylphenyl)propionic acid (Ketoprofen) with various bulky amines has produced a series of highly active antiinflammatory agents that have reduced intestinal ulcerogenicity and have better therapeutic ratios in the 21-day adjuvant arthritis assay in rats than currently marketed nonsteroidal antiinflammatory drugs. Activity is maintained on reduction of these 2-(3-benzoylphenyl)propyl bulky amines to the corresponding alcohols or methylene analogues, on conversion of the ketone function to a primary amine or oxime, and on introduction of a 4-halo substitutent (Cl or F) on the terminal aromatic ring. Removal of the alpha-CH3 group greatly reduces the antiinflammatory activity of the series. These compounds have been synthesized by the reductive amination of 2-(3-bromophenyl)propionaldehyde with the respective amine followed by lithiation of this product and condensation with the appropriate benzonitrile.
Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Ketoprofen/chemical synthesis , Phenylpropionates/chemical synthesis , Animals , Arthritis, Experimental/drug therapy , Chemical Phenomena , Chemistry , Drug Evaluation, Preclinical , Edema/drug therapy , Indicators and Reagents , Ketoprofen/analogs & derivatives , Ketoprofen/therapeutic use , Magnetic Resonance Spectroscopy , Male , Rats , Rats, Inbred Strains , Structure-Activity RelationshipABSTRACT
A critical review of the literature was undertaken to determine if there is valid data to support the contention that oral lichen planus represents a disease with significant potential for malignant degeneration. Although there are reports alleging such a relationship, there is insufficient documented evidence to state with any degree of confidence that oral lichen planus, in itself, represents a premalignant state.
