Subject(s)
Hypersensitivity, Immediate/immunology , Receptors, G-Protein-Coupled/physiology , Receptors, Histamine/physiology , Signal Transduction/physiology , Histamine/physiology , Humans , Lymphocytes/immunology , Lymphocytes/metabolism , Matched-Pair Analysis , Phosphorylation , Promoter Regions, Genetic , Receptors, Histamine H4 , STAT1 Transcription Factor/metabolism , STAT6 Transcription Factor/metabolismABSTRACT
OBJECTIVE AND DESIGN: Pyrethroids are claimed to have a low human toxicity with some neuro- and immunotoxicity. The objective of this study was to investigate the immunotoxicological properties of six commercially used pyrethroids, including natural pyrethrum and synergist piperonyl-butoxide (PBO). MATERIAL AND METHODS: PHA-stimulated cultures of T-helper lymphocytes and blood basophil incubates from nonatopic and atopic patients (IgE > 1000 IU) provided cytokine and histamine determination. Western blot analysis was used for the measurement of Th2-specific signal transducer and activator of transcription-6 (STAT6). Pyrethroids and xenobiotics were added 4 h post-plating. RESULTS: We demonstrated that interferon-gamma (IFN-gamma) production and expression was correlated with lymphocyte proliferation, however, interleukin-4 (IL-4) was down-regulated at the end of the 3 day culture. Atopics showed significantly higher IL-4 activity than nonatopics. Pyrethroids inhibited IFN-gamma and IL-4 in both groups at around 10(-5) M. Only fenvalerate and S-bioallethrin combined with 10-fold PBO in the atopic-enriched blood basophil incubates caused a weak but significant increase in histamine release. Histamine acted bidirectionally on STAT6, but pyrethroids inhibited the intracellular Th2-specific STAT6 more effectively in atopics than in nonatopics. CONCLUSION: It can be suggested that pyrethroids inhibit signal transduction in human lymphocytes ex vivo, and do not act via lymphocyte-influencing histamine release.
Subject(s)
Hypersensitivity, Immediate/physiopathology , Insecticides/pharmacology , Pyrethrins/pharmacology , Signal Transduction/drug effects , T-Lymphocytes, Helper-Inducer/drug effects , Adult , Blotting, Western , Cell Differentiation/drug effects , Cells, Cultured , Cytokines/biosynthesis , Female , Histamine/pharmacology , Histamine Release/drug effects , Humans , Interferon-gamma/biosynthesis , Interferon-gamma/genetics , Interleukin-4/biosynthesis , Interleukin-4/genetics , Male , No-Observed-Adverse-Effect Level , RNA/chemistry , RNA/isolation & purification , Tetrazolium Salts , ThiazolesSubject(s)
Basophils/metabolism , Histamine Release/drug effects , Insecticides/pharmacology , Pyrethrins/pharmacology , Adult , Basophils/drug effects , Humans , In Vitro Techniques , Mast Cells/drug effects , Mast Cells/metabolism , N-Formylmethionine Leucyl-Phenylalanine/pharmacology , STAT6 Transcription Factor , Signal Transduction/drug effects , Trans-Activators/biosynthesisSubject(s)
Insecticides/adverse effects , Nervous System Diseases/chemically induced , Pyrethrins/adverse effects , Allethrins/urine , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Female , Hair/chemistry , Humans , Insecticides/urine , Interferon-gamma/metabolism , Interleukin-4/metabolism , Leukocytes, Mononuclear/metabolism , Middle Aged , Nervous System Diseases/immunology , Pesticide Synergists/immunology , Piperonyl Butoxide/immunology , Pyrethrins/immunology , Pyrethrins/urine , Skin TestsABSTRACT
Synthetic pyrethroids are increasingly used as insecticides and are claimed to have a relatively low human toxicity. The aim of this study was to examine the in vitro effects of the synthetic pyrethroid S-bioallethrin alone and in combination with the common synergist piperonyl-butoxide (PBO) on human blood lymphocytes and basophils in atopic individuals and non-atopic control subjects. S-bioallethrin and PBO also caused inhibition of lymphocyte proliferation (MTT-test) after a 72-h culture period in a concentration dependent manner. In contrast to the MTT-measurements the combined agents are more effective in inhibiting interleukin-4 (IL-4)- and interferon-gamma (IFN-gamma)-production. The regulatory IL-4/IFN-gamma balance showed a significant difference between atopic and non-atopic subjects after a culture period of 24-48 h in the presence of micromolar S-bioallethrin (P < 0.001). Furthermore S-bioallethrin, PBO and the combined agents induced histamine release from human basophils. Although this effect was little compared to histamine liberators like FMLP and anti-IgE, the response to S-bioallethrin and PBO was significantly different in atopic donors compared with non-atopics (P < 0.01). In scratch test experiments 4 of 18 tested atopic volunteers showed positive reaction (wheals and flares) to S-bioallethrin and permethrin, whereas no reaction could be measured in the control group (age-matched). These findings demonstrate the immuno- and allergo-toxicological properties of the synthetic pyrethroid S-bioallethrin combined with the synergistic PBO using this in vitro approach with human lymphocytes and basophils.
Subject(s)
Allethrins/toxicity , Insecticides/toxicity , Piperonyl Butoxide/toxicity , T-Lymphocytes/drug effects , Adolescent , Adult , Cells, Cultured , Female , Histamine Release/drug effects , Humans , Interferon-gamma/biosynthesis , Interleukin-4/biosynthesis , Male , Middle Aged , Skin TestsSubject(s)
Allethrins/adverse effects , Basophils/drug effects , Insecticides/adverse effects , Piperonyl Butoxide/adverse effects , Pyrethrins/adverse effects , T-Lymphocytes/drug effects , Adolescent , Adult , Cells, Cultured , Drug Hypersensitivity , Female , Histamine Release/drug effects , Humans , Interferon-gamma/biosynthesis , Interleukin-4/biosynthesis , Male , Middle Aged , Permethrin , Pesticide Synergists/adverse effectsABSTRACT
The article describes uterus duplex and unilateral agenesis of the kidney in two sisters. Although this combined malformation has been described in literature in about 100 cases, it would seem that it occurred in one and the same family in only one case, namely, in mother and daughter. If agenesis of the kidney or a malformation of the uterus is found in a patient, the physician should look for a combined malformation in other members of the family.
Subject(s)
Abnormalities, Multiple/genetics , Kidney/abnormalities , Uterus/abnormalities , Abnormalities, Multiple/diagnostic imaging , Adolescent , Adult , Female , Humans , Hysterosalpingography , Kidney/diagnostic imagingABSTRACT
Two cases with calcifications of the pancreatic duct are demonstrated. The degree exceeds similar published calcifications. In both cases the diagnostic investigation had to be limited to non-invasive methods.
