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331.
Raimo Pohjanvirta Jouko Tuomisto Kaarina Vikkula 《Basic & clinical pharmacology & toxicology》1988,63(4):240-247
Abstract: A salient sign of fatal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication is dramatic body weight loss accompanied by hypophagia. Yet, the nature of this wasting syndrome is unknown. As all of the current leptogenic (weight reducing) drugs exert their action by affecting aminergic neurotransmission, this study set out to screen the reversibility of TCDD-induced anorexia with the following agents modulating aminergic neurotransmission: amphetamine, amperozide, chlordiazepoxide, clonidine, haloperidol, morphine, PCPA, phenoxybenzamine, reserpine and sotalol. In addition, dexamethasone, indomethacin, and insulin were included in the drug battery. The agents were administered subcutaneously to adult male Long-Evans rats over a period lasting from 3 to 14 days. Half of each drug group was concomitantly exposed to a lethal dose of TCDD (20 μg/kg). None of the regimens were able to mitigate the wasting syndrome. TCDD proved to markedly diminish the nocturnal feed intake while practically sparing daytime feed consumption. Insulin increased the daytime feeding of TCDD-exposed rats, and the termination of treatment resulted in almost total aphagia in this group. Amphetamine, dexamethasone, PCPA, and reserpine caused weight loss in drug control rats and aggravated the action of TCDD. However, clonidine had no effect on the weight of control rats but accelerated weight decline in TCDD-cotreated animals. TCDD seemed to have a somewhat minor influence on drinking than on feeding. Clonidine stimulated water intake in controls but not in TCDD-exposed rats. These results suggest that aminergic neurotransmission is not specifically or crucially affected by TCDD, but further studies are needed to confirm this conclusion. 相似文献
332.
TCDD reduces serum melatonin levels in Long-Evans rats 总被引:2,自引:0,他引:2
333.
Comparison of histamine assay methods in measuring in vitro-induced histamine release in patients with allergic rhinitis 总被引:1,自引:1,他引:0
histamine release tests using whole blood were applied in testing in vitro Type I birch allergic reaction in two patients with allergic rhinitis. Heparinized blood was incubated with varying dilutions of allergen for 30 min at +37 degrees C. After centrifugation of the blood, plasma was separated and the liberated histamine was analysed by histamine radio enzyme assay (REA), high performance liquid chromatography (HPLC) with post-column derivatization system or radio immuno assay (RIA), and the results obtained by these methods were compared. REA and HPLC gave similar results, while RIA gave somewhat higher values, but was less sensitive. 相似文献
334.
Tissue distribution, metabolism, and excretion of 14C-TCDD in a TCDD-susceptible and a TCDD-resistant rat strain 总被引:1,自引:0,他引:1
R Pohjanvirta T Vartiainen A Uusi-Rauva J M?nkk?nen J Tuomisto 《Pharmacology & toxicology》1990,66(2):93-100
A comparative study was carried out in the most TCDD-resistant [Han/Wistar (H/W), LD50 greater than 3000 micrograms/kg] and the most TCDD-susceptible [Long-Evans (L-E), LD50 about 10 micrograms/kg] rat strain to assess the significance of kinetic factors in TCDD toxicity. Young adult males of both strains were administered 5 micrograms/kg (1.9 microCi/kg) 14C-TCDD intraperitoneally. Four rats per strain were killed at 4 hr, 1, 4, 8, 16, and 32 days after exposure. A total of 22 tissues along with blood and serum were sampled for liquid scintillation counting. From half of the animals, daily urine and faeces were also analyzed. In addition, 3 rats per strain were given 50 micrograms/kg (19 microCi/kg) 14C-TCDD and prepared for whole-body autoradiography after 1, 4 or 8 days. The livers of two rats per strain killed at 4 hr, 4 or 16 days, and the excreta from two rats of both strains collected on days 1-4, 5-8, 13-16, and 29-32 after exposure were analyzed for metabolites of TCDD by high pressure liquid chromatography. The label was mainly excreted in faeces as metabolites of TCDD, and the half-life of elimination was 20.8 (L-E) or 21.9 (H/W) days. A very similar overall distribution pattern was observed in both strains irrespective of dose, and the liver was the major site of accumulation. Practically all liver 14C-activity was found as the parent compound. Moderate strain-related differences were observed in the thyroid, thymus, prostate, adrenals, and brown and white fat, where lower values were recorded in H/W rats.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
335.
336.
337.
Alaluusua S Calderara P Gerthoux PM Lukinmaa PL Kovero O Needham L Patterson DG Tuomisto J Mocarelli P 《Environmental health perspectives》2004,112(13):1313-1318
Children's developing teeth may be sensitive to environmental dioxins, and in animal studies developing teeth are one of the most sensitive targets of toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Twenty-five years after the dioxin accident in Seveso, Italy, 48 subjects from the contaminated areas (zones A and B) and in patches lightly contaminated (zone R) were recruited for the examination of dental and oral aberrations. Subjects were randomly invited from those exposed in their childhood and for whom frozen serum samples were available. The subjects were frequency matched with 65 subjects from the surrounding non-ABR zone for age, sex, and education. Concentrations of TCDD in previously analyzed plasma samples (zone ABR subjects only) ranged from 23 to 26,000 ng/kg in serum lipid. Ninety-three percent (25 of 27) of the subjects who had developmental enamel defects had been < 5 years of age at the time of the accident. The prevalence of defects in this age group was 42% (15 of 36) in zone ABR subjects and 26% (10 of 39) in zone non-ABR subjects, correlating with serum TCDD levels (p = 0.016). Hypodontia was seen in 12.5% (6 of 48) and 4.6% (3 of 65) of the zone ABR and non-ABR subjects, respectively, also correlating with serum TCDD level (p = 0.05). In conclusion, developmental dental aberrations were associated with childhood exposure to TCDD. In contrast, dental caries and periodontal disease, both infectious in nature, and oral pigmentation and salivary flow rate were not related to the exposure. The results support our hypothesis that dioxins can interfere with human organogenesis. 相似文献
338.
Effect of TCDD on mRNA expression of genes encoding bHLH/PAS proteins in rat hypothalamus 总被引:1,自引:0,他引:1
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) brings about a wide variety of toxic and biochemical effects via an AH receptor (AHR)-mediated signalling pathway. Wasting syndrome and acute lethality are TCDD-induced endpoints showing a striking sensitivity difference between two rat strains, TCDD-sensitive Long-Evans (Turku/AB) (L-E) and TCDD-resistant Han/Wistar (Kuopio) (H/W). These rat strains were used to study hypothalamic effects of TCDD on expression of genes encoding AHR-regulated bHLH/PAS proteins potentially involved in molecular pathogenesis of the wasting syndrome. In addition, two well-established target genes of TCDD, CYP1A1 and CYP1A2 were also examined. Quantitative RT-PCR was used to measure mRNA levels in hypothalamus, which is a major center of food intake and body weight regulation. At both 6 and 96 h after a single dose of 50 microg/kg TCDD, significant elevations were found in mRNA levels of AHR repressor (AHRR), CYP1A1 and CYP1A2, but not those of AHR, ARNT or ARNT2. Likewise, TCDD (100 microg/kg) did not alter the expression of SIM1, implicated in the suppressive impact of TCDD on food intake, nor that of PER2, involved in regulation of circadian rhythms. Differences between H/W and L-E rats appeared in constitutive levels of AHR and ARNT and in TCDD-induced levels of CYP1A2, AHRR, AHR and ARNT, which all were about two- to four-fold lower in H/W rats. Thus, although the changes found do not account for the wasting syndrome, expression of all principal genes of the AHR-signalling pathway in rat hypothalamus make it a candidate target for TCDD. 相似文献
339.
Huotari M Passlin M Nordberg HL Forsberg M Kotisaari S Tuomisto L Shintani F Tanaka KF Reenilä I Laitinen K Männistö PT 《Journal of neuroscience methods》2001,109(1):47-52
6-Nitronoradrenaline, a bioactive compound recently identified in the brain, is known to inhibit catechol-O-methyltransferase. To study its effect on dopamine metabolism, it was administered into rat striatum via a microdialysis probe. Other nitrated catechols (6-nitrodopamine, 6-nitro-DOPAC and 5-nitro-HVA) were studied for comparison. Tolcapone, a selective catechol-O-methyltransferase inhibitor, was used as a positive reference compound. Both 6-nitronoradrenaline and tolcapone increased striatal extracellular dopamine levels during the perfusion (at 100 microM concentration but not at 10 microM) and decreased the efflux of homovanillic acid. Tolcapone, but not other nitrated catechols, increased 3,4-dihydroxyphenylacetic acid efflux. None of the compounds inhibited MAO-B activity at 100 microM or lower. At 1 mM, 6-nitrodopamine inhibited MAO-B by 60%. Compared to tolcapone, other nitrated catechols were very weak COMT inhibitors in vitro. Neither tolcapone nor 6-nitronoradrenaline modified the metabolism of L-dopa which was given peripherally. In binding studies, both 6-nitronoradrenaline and other nitrocatechols failed to affect the dopamine transporter even at high micromolar concentrations. In conclusion, exogenous 6-nitronoradrenaline can act as a COMT inhibitor in the striatum and elevate striatal dopamine levels without inhibiting dopamine reuptake. Whether endogenous 6-nitronoradrenaline can be formed also in vivo in the striatum and act as a regulator of dopaminergic tone remains to be determined. 相似文献
340.
冬天干冷的气候会令全身肌肤可能因此越来越干燥、粗糙,失去水分和光泽。选择有良好滋润功效的沐浴露和身体乳液,让你在寒冷冬天也能拥有一身光滑细腻的肌肤。[编者按] 相似文献