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1.
The time courses of fecal excretion and tissue distribution of metabolites derived from 2,2′,4,5,5′-pentachlorobiphenyl (CB101) and 2,2′,3,4′,5′,6-hexachlorobiphenyl (CB149) were investigated in male Wistar rats. The metabolism of both congeners involved primarily hydroxylation at the 3-position, and methylthiolation at the 4-position. Metabolites distributed in tissue were dominated by different ratios of 3- and 4-methylsulfonyl (MeSO2) metabolites. The 3-/4-MeSO2 metabolite ratios in liver and adipose tissue for both congeners were 0.41–0.61 at day 4, and then increased to 0.85–1.00 for up to day 42. In contrast, the ratios in lung were 0.03–0.04, and then decreased to 0.01. Compared to the unchanged PCBs at day 42, the distribution ratios of 3-MeSO2 metabolites were greater in the order of liver (0.46 for CB101 and 0.21 for CB149) > kidney > blood > lung > adipose tissue, whereas those of 4-MeSO2 metabolites were in the order of lung (9.50 for CB101 and 4.00 for CB149) > kidney > blood > liver > adipose tissue, indicating the different binding affinity of 3-MeSO2 metabolites in liver from that of 4-MeSO2 metabolites in lungs of rats. Furthermore, the structure-tissue affinity relationship for 3-MeSO2 metabolites was investigated, following the administration of 11 3-MeSO2-PCB congeners to rats. The results indicated that the retention potential of 3-MeSO2 metabolites in the liver largely depends on the ortho-chlorine substitution in the biphenyl ring rather than the degree of chlorination. Received: 17 July 1998/Accepted: 11 January 1999  相似文献   

2.
The toxicity of 3,3,4,4-tetrachloroazobenzene (TCAB) and 3,3,4,4-tetrachloroazoxybenzene (TCAOB) to chick embryos was examined. TCAB or TCAOB was dissolved in corn oil and injected into the air cell of fertile chicken eggs. The time of injection had a major effect on embryo mortality as eggs injected with TCAB or TCAOB on the fourth day of incubation had a higher incidence of embryo mortality than eggs injected on days 11–13. Both TCAB and TCAOB were more toxic than all other chemicals that have been tested in the chick embryo with the exception of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Comparing the potency of the two compounds, TCAOB was more potent than TCAB in the chick embryo with an estimated LD50 of 12 ng and 44 ng respectively. Rump edema was the major abnormality observed in embryos treated with either TCAB or TCAOB. Other malformations included altered feather pattern and lack of down, hemorrhage, external viscera, reduced body size, failure to withdraw the yolk sac, beak malformation, dilation of blood vessels, and monomicropthalmia. The results of this investigation suggest that both TCAB and TCAOB are teratogenic in the chick embryo.This work was presented in part at the Annual Meeting of the Society of Toxicology, San Diego, CA, March 1–5, 1981.  相似文献   

3.
4.
The addition of 100 (g/L of Aroclor® 1242 (A1242) or 2,5,2,5-tetrachlorobiphenyl (TeCB) during 10 week chronic toxicity tests withHyalella azteca resulted in complete mortality. There were no effects on survival, growth, or reproduction after addition of 30 g/L. Toxic effects were observed at tissue levels of between 30 and 180 g/g on a wet weight basis, and tissue levels appear to be a better indicator of toxicity than levels in water. No toxic effects were observed after additions of up to 2,700 g/L of the coplanar congener 3,4,3,4-TeCB.H. azteca has the ability to avoid accumulating in excess of 140 g/g 3,4,3,4-TeCB. The amount taken up was proportional to the amount added in water up to 100 g/L, but was constant at higher additions, possibly accounting for its relatively low toxicity. The low toxicity of the coplanar congener, as compared to the non-coplanar 2,5,2,5-TeCB, is in direct contrast to the high toxicity of coplanar PCB congeners to mammals and may be associated with slower rates of aromatic hydrocarbon metabolism in amphipods. Polychlorinated biphenyl levels measured in amphipods from Lake Ontario are approximately 100-fold below levels associated with toxicity inH. azteca, but are above levels which, through biomagnification up the food chain, lead to salmonid residues in excess of 2 g/g, a tolerance limit for human consumption.  相似文献   

5.
The excretion and tissue retention of three 14C-labeled lower chlorinated biphenyls were examined in prepubertal male and female Sprague-Dawley rats following IV administration. Urine and feces were collected individually at different time intervals up to 72 h for pharmacokinetic analyses. After 72 h, different organs were removed and extracted in acetone:hexane (1:1, v/v) to determine radioactivity. Within the first 10 h after dosing, 2,2′,5-trichlorobiphenyl (PCB 18) was rapidly excreted in urine (8–18% of the administered dose), whereas only 0.6–0.8% of 2,2′,4,4′-tetrachlorobiphenyl (PCB 47) and 0.3–0.8% 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) were found in urine during this time period. The half-life of elimination was shortest for PCB 18 (37.5 to 49.2 h). The half-lives for PCB 47 and PCB 77 were 351 to 672 h and 152 to 186 h, respectively. The cumulative total excretion (urinary + fecal) of PCB 18 within 72 h was 51–62%, of PCB 77 was 22–25%, and of PCB 47 was 7–10%. No parent PCBs were detected in urine. PCB 47 accumulated preferentially in adipose tissues (subcutaneous fat > mesenteric fat); relatively high levels of PCB 47 were also found in adrenals, ovaries, lungs, liver, and skin. The highest concentration of PCB 77 was found in serum, followed by adipose tissues. Very low concentrations of PCB 18 were found in most tissues; the highest being found in serum, followed by ovaries and adrenal glands. This study suggests that prepubertal rats retain higher short-term serum levels and have lower excretion rates than adult rats. Received: 3 February 1998/Accepted: 16 August 1998  相似文献   

6.
Prenatal exposure of rats to 3,4,3,4-tetrachlorobiphenyl (4CB) at 3 mg/kg/day from day 6 through day 18 of gestation produced a high incidence of perinatal mortality. Although the fine structure of fetal liver at day 19 appeared normal, significant changes were manifest in newborn pups. These alterations included a distention of cisternae of the rough endoplasmic reticulum and conspicuous proliferation of smooth membrane elements, which persisted in survivors for several weeks. In addition, mitochondria often appeared condensed with an atypical distribution of cristae. These changes were accompanied by a postnatal induction in the activity of liver UDP-glucuronyltransferase. In treated litters, 3-week-old pups had activity levels of the enzyme three times that of the controls.  相似文献   

7.
2,2′,4,4′-Tetrabromodiphenyl ether (BDE47) is an environmental contaminant. To determine the reproductive toxicity, we studied groups of adult male mice and found that the rate of sperm capacitation was decreased significantly in three BDE47-exposed groups (0.0015, 0.045 and 30 mg kg?1 day?1). Sperm motility parameters (MOT, PRO, VCL and BCF) after capacitation were also declined in treated groups. Moreover, exposure to BDE47 at concentrations of ≥0.045 mg kg?1 day?1 caused increased germ cell loss and apoptosis in some seminiferous tubules. Our results suggest that short-term exposure to low-dose BDE47 may have adverse effects on semen quality and spermatogenesis in adult male mice.  相似文献   

8.
Several PCB congeners, present in commercial PCB formulations, are chiral. These PCBs can undergo enantiomeric enrichment in many animal species and in humans due to currently uncharacterized enantioselective biotransformation processes. To investigate if certain cytochrome P-450 enzymes (CYPs), such as CYP2B’s, are responsible for this enantiomeric enrichment, we investigated the enantioselective disposition of (±)-PCB 136 in female mice after induction of different CYP enzymes by pretreatment with corn oil alone, β-naphthoflavone (CYP1A’s), phenobarbital (CYP2B’s), or dexamethasone (2B’s and 3A’s), followed by oral PCB administration. PCB 136 levels were significantly lower in phenobarbital- and, to a lesser extent, in dexamethasone-pretreated animals, presumably due to the induction of PCB 136 metabolizing enzymes. Although (+)-PCB 136 was enriched in all tissues, none of the pretreatments altered the enantioselective disposition of PCB 136 in a manner that suggests a particular CYP subfamily as the cause of the enrichment of (+)-PCB 136. Fecal PCB levels and enantiomeric fraction values changed over time in a manner consistent with slower digestive motility in the mice pretreated with phenobarbital and dexamethasone. Overall, this study does not support the hypothesis that metabolism by CYP2B enzymes is responsible for the enrichment of (+)-PCB 136 in mice.  相似文献   

9.
《Nutrition Research》1986,6(5):589-599
When the concentration and turnover of the cyclic nucleotides cyclic 3′, 5′-adenosine monophosphate (cAMP) and cyclic 3′,5′-guanosine monophosphate (cGMP) were measured in the thymus, spleen and cervical lymphnodes of xats subjected to various models of malnutrition, and these same parameters of cAMP alone assessed in their liver, kidney and brain, undernutrition has been found to modify cyclic nucleotide metabolism. When the results on nucleic acid and protein metabolism are taken into consideration with the changes in cyclic nucleotide metabolism, it was noted that the various phases of the cell cycle are prolonged or blocked in the organs of malnourished rats. These data indicate a correlation between cyclic nucleotide metabolism and impaired immune responsiveness seen commonly in undernourished rats.  相似文献   

10.
Two tetrachlorobiphenyls (2,2,4,4-tetraCB and 3,3,4,4-tetraCB) had different effects on the longevity of adult female house flies (Musca domestica), depending on enzyme levels at dosing. Twenty-four-hour acute toxicities of the two tetrachlorobiphenyls were also compared with one trichlorobiphenyl (2,2,5-triCB) at different enzyme levels. 2,2,4,4-tetraCB killed more than 90% of the flies within 12 h at the highest dose (1,667 ppm, g/g); however, the toxicity of the moderate dose (1,250 ppm) was age-dependent and greater in 1- and 15-day-old flies and lower in 5-day-old flies. Daily mortality patterns of the lower doses (390 and 833 ppm) were similar to the control. LT50s (time for 50% death) were also different in different age groups at the moderate dose. The toxicity of 3,3,4,4-tetraCB was similar to the control in all age groups, with a slight increase in the early mortalities and a decrease in the LT50s at the highest (1,200 ppm) dose.The twenty-four-hour lethality of 2,2,4,4-tetraCB was very high, even at the lower doses in 1- and 15-day-old flies. Lower doses were least toxic at day 5, when the levels of cytochrome P450 enzymes were at the highest. On the other hand, the acute toxicity of 2,2,5-triCB increased from 5 and 15% in 1- and 15-day-old flies, respectively, to about 50% in 5-day-old flies, suggesting bioactivation of 2,2,5-triCB. The acute toxicity of 3,3,4,4-tetraCB was negligible in all ages of house flies.  相似文献   

11.
Diets supplemented with 0.01 or 0.05 ppm (mg/kg) of 3,4,5,3,4,5-hexachlorobiphenyl (345-HCB) were fed to mink to investigate the toxicological manifestations of this toxic polychlorinated biphenyl congener in a sensitive species. Dietary exposure of mink to 0.05 ppm 3,4,5,3,4,5-hexachlorobiphenyl for 135 days resulted in 50% mortality while no deaths occurred on 0.01 ppm 345-HCB. Clinical signs of toxicity included anorexia, bloody stools, disrupted molting patterns, and thickened, elongated and deformed nails. Ascites and gastric ulcers were present in animals that died. Statistically significant increases in liver, kidney, and adrenal gland weights were found in the 345-HCB-treated mink. Decreases in total and free triiodothyronine concentrations were observed in mink fed the 345-HCB-treated diets and total thyroxine was decreased in the mink fed 0.05 ppm 345-HCB. No consistent histopathologic lesions were found in the thyroid or adrenal glands of the 345-HCB-treated mink, nor were there any statistically significant differences between the 345-HCB-treated and the control mink in serum epidermal growth factor levels, plasma 17-estradiol and progesterone concentrations, hepatic aminopyrine N-demethylase, and benzo()pyrene hydroxylase activities, hypothalamic norepinephrine, dopamine, and serotonin concentrations or in the incorporation of (3H) thymidine by concanavalin-A-stimulated lymphocytes.Published with the approval of the Michigan Agricultural Experiment Station as Journal Article Number11963.  相似文献   

12.
Physicochemical parameters (vapor pressure, water solubility, Henrys law constant) and biological activities of two halogenated natural products frequently detected in marine samples and food were determined. Synthetic 2,3,3,4,4,5,5-heptachloro-1-methyl-1,2-bipyrrole (Q1) and 2,4,6-tribromoanisole (TBA) were available in pure form. The physicochemical parameters were in the range of anthropogenic chlorinated compounds of concern. The aqueous solubilities at 25°C (Sw,25) of Q1 and TBA were 4.6 g/L and 12,200 g/L, respectively, whereas subcooled liquid vapor pressures were 0.00168 Pa (Q1) and 0.06562 Pa (TBA) as measured by the gas chromatographic–retention time technique. Q1 was negative by established test systems for the determination of ethoxyresorufin-O-deethylase (EROD) induction and by sulforhodamine B assay. EROD induction potency was at least 10–7 times lower than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). At a relatively high concentration (20 M), Q1 inhibited specific binding of 2 nM [3H]TCDD to the in vitro-expressed human aryl hydrocarbon receptor (AHR) by 18%; lower concentrations showed no effect. Molecular modeling showed that Q1 is nonplanar, consistent with its relatively modest affinity as an AHR ligand. When tested for cell-growth inhibitory/cytocidal activity in human tumor cells, Q1 was only marginally, if at all, active with an IC50 value >50 M compared with five to ten times lower IC50 values for potent cytotoxins tested in the test system used. Furthermore, standard pesticide tests on insecticidal, herbicidal, and fungicidal activity did not provide any significant activity at highest concentrations. For TBA, the results in all tests were comparable with Q1. The SRB assay was also applied to the halogenated natural product 4,6-dibromo-2-(2,4-dibromo)phenoxyanisole, but no toxic response was found. Although it was apparent that Q1 and TBA had been proven to have relatively low biological activity in all tests performed, further research is necessary to clarify whether metabolites of the compounds eventually may possess a risk to humans or other living organisms. Nevertheless, the role of Q1 in nature remains uncertain.  相似文献   

13.
A two compartment pharmacokinetic model was developed which describes the uptake and elimination of 5,5,6-trichlorobiphenyl (TCB) and pentachlorophenol (PCP) in the midge, Chironomus riparius. C. riparius were exposed to nominal TCB (2 g L–1) and PCP (9 g L–1) concentrations during a 16 h static uptake phase. Depuration was determined over approximately 45 h using a flowthrough system without feeding. The uptake clearance (P) was 330±61 ml g–1 midge h–1 for TCB and 55±4 ml g–1 midge h–1 for PCP, while measured bioconcentration factors (BCF) were 35,900 and 458 for TCB and PCP, respectively. Overall, the clearance-volume-based pharmacokinetic model predicted BCF values that were consistent with published values as well as with BCF values obtained from the octanol-water partition coefficient (KOW).  相似文献   

14.
Objectives: In the present study, effects of 3′,4′-dihydroxyflavonol (DiOHF) on anxiety-like behavior, and learning and memory were investigated in a model of transient global cerebral ischemia and reperfusion.

Methods: The animals were assigned to sham-operated, ischemia, and two DiOHF-treated (10 mg/kg i.p.) groups. DiOHF was administered at 1 hour before and immediately after the ischemia. Male rats were subjected to bilateral common carotid artery occlusion to induce acute cerebral ischemia for 20 minutes, followed by reperfusion for 7 days. The openfield, elevated plus maze (EPM), and Morris water maze tests were used to evaluate the effects of DiOHF treatment on ischemia-induced locomotor activity, anxiety-like behavior, and spatial and recognition memory impairments, respectively.

Results: In the open field test, locomotor activity in the ischemic rats was not altered 6 days after the ischemia, nor was anxiety-like behavior, which was evaluated with the EPM (P > 0.05). In the water-maze test, cerebral ischemia significantly decreased the exploration time in the target quadrant, and the platform crossing counts were lower (P < 0.05) in the probe trial test; this memory impairment was significantly improved by DiOHF applied 1 hour before and immediately after ischemia (P < 0.05).

Discussion: All together, these findings suggest that DiOHF reverses spatial learning and memory deficits resulting from transient global ischemia but has no significant effect on anxiety-like behavior.  相似文献   


15.
Objective To explore the role of TGF-βand TGIF in the pathogenesis of endometriosis. Methods The expression of TGF-β and TGIF was detected by immunohistochemistry method in the ectopic and eutopic endometrium of 30 cases with endometriosis (ec-topic endometrium group and eutopic endometrium group) and in the normal endometrium of 40 cases without endometriosis (control group). Result The expression of TGF -β in ectopic endometrium group was significantly higher than that in eutopic endometrium group and control group (P < 0.05). There was no significant difference in the expression of TGF- βbetween eutopic endometrium group and control group(P > 0.05). The expression of TGIF in ectopic endometrium group was significantly lower than that in eutopic endometrium group and control group( P <0.05). There was no significant difference in the expression of TGIF between eutopic endometrium group and control group(P > 0.05). There were negative correlation between the expressions of TGF - β and TGIF in ectopic endometrium group and eutopic endome-trium group(rs= - 0.769, - 0.549, P < 0.05). Conclusion The abnormal expression of TGF-β and TGIF in ectopic endometrium of pa-tients with endometriosis may be associated with the genesis and progression of endometriosis.  相似文献   

16.
[目的]分析1990~1999年我国城市和农村居民糖尿病死亡率的现况特点并预测未来5年的变化趋势.[方法]根据<全国卫生统计年报>资料,对我国1990至1999年糖尿病死亡率的现况进行流行病学分析,并利用灰色动态模型GM(1.1)预测我国2000至2005年城市和农村糖尿病死亡率趋势.[结果]城市1999年糖尿病死亡率为15.37/10万而农村为5.13/10万,分别是1990年死亡率的1.89倍和1.71倍;女性的死亡率高于男性,城市和农村男女死亡率之比分别为0.63∶1和0.76∶1;根据1990~1999死亡率所建立的城市的灰色模型预测方程为t=-106.481 7×(1-e0.074 58t)-Yt-1(t=1,2,...,N),而农村的方程为t=-33.605 3×(1-e0.075 37t)-Yt-1(t=1,2,...,N);预测到2005年我国城市和农村糖尿病死亡率将分别达到25.24/10万人和8.15/10万人;精度检验证明了城市和农村的预测模型拟合良好而外推测值可信.[结论]我国人群糖尿病死亡率上升趋势明显,提示有关部门应加强防治力度;灰色模型GM(1.1)能够较好地预测糖尿病死亡率的近期变化趋势.  相似文献   

17.
The doctor–patient relationship has been widely studied in biomedicine. However, little research has focused on similar provider–client relationships in holistic healthcare forms. Based on ethnographic research with acupuncture clients and practitioners, the authors found that participants used specific models of health to understand and develop subsequent models of interaction, and in doing so, provided a clear critique of biomedicine. This article offers a brief overview of major models of healthcare, including biomedical, biopsychosocial, and holistic. The authors present current models of interaction that have been used to understand the biomedical doctor–patient relationship, and discuss the utility of both sets of models as they relate to the ethnographic observations. Although a particular model of health (biomedical or holistic) does not necessitate a particular model of health interaction (paternalism, consumerism, or collaboration), participants' attempts to tie these 2 realms together are important to understanding practitioner–patient relationships in all healthcare situations.  相似文献   

18.
The usefulness of an isotopic in vitro assay in the field was evaluated by comparing its results with the therapeutic response determined by the simplified WHO in vivo test in symptomatic Cameroonian patients treated with chloroquine. Of the 117 enrolled patients, 102 (87%) completed the 14-day follow-up, and 95 isolates obtained from these patients (46 children, 49 adults) yielded an interpretable in vitro test. A total of 57 of 95 patients (60%; 28 children and 29 adults) had an adequate clinical response with negative smears (n = 46) or with an asymptomatic parasitaemia (n = 11) on day 7 and/or day 14. The geometric mean 50% inhibitory concentration of the isolates obtained from these patients was 63.3 nmol/l. Late and early treatment failure was observed in 29 (30.5%) and 9 (9.5%) patients, respectively. The geometric mean 50% inhibitory concentrations of the corresponding isolates were 173 nmol/l and 302 nmol/l. Among the patients responding with late and early treatment failure, five isolates and one isolate, respectively, yielded a discordant result (in vivo resistance and in vitro sensitivity). The sensitivity, specificity, and predictive value of the in vitro test to detect chloroquine-sensitive cases was 67%, 84% and 86%, respectively. There was moderate concordance between the in vitro and in vivo tests (kappa value = 0.48). The in vitro assay agrees relatively well with the therapeutic response and excludes several host factors that influence the results of the in vivo test. However, in view of some discordant results, the in vitro test cannot substitute for in vivo data on therapeutic efficacy. The only reliable definition of "resistance" in malaria parasites is based on clinical and parasitological response in symptomatic patients, and the in vivo test provides the standard method to determine drug sensitivity or resistance as well as to guide national drug policies.  相似文献   

19.
20.

Background

In Benin, malaria was the leading cause of hospital consultation for children less than 5 years old (47.2%), and for all patients not hospitalized (42.3%). Its incidence among those who attended a health facility was respectively 42.9% and 17%. To address this problem, the National Program for the Fight against Malaria undertook, in 2011, a mass campaign of distribution of Long-Lasting Insecticidal Nets (LLINs). In addition to this strategy, the program decided to implement Indoor Residual Spraying in 7 of the 9 municipalities of Atacora department, which is one of the most malaria endemic areas. The objective of this study was to see if adding the IRS to the LLINs (municipality of Kouandé) strategy is cost-effective, as compared to the LLINs-only strategy (municipality of Copargo), in highly malaria endemic areas.

Method

This study was a cross-sectional study of the implementation of the IRS from June 2011 to July 2011. Regarding the selection of health workers, managers of the malaria program, and partners of implementation of the IRS, a reasoned choice was made. The data collection consisted mainly of a series of interviews with people responsible for resource management and the exploitation of documents provided by them.

Results

After the implementation of LLNs + IRS the annual incidence of malaria in health facilities decreased significantly at Kouandé-Centre and at Guilmaro. In the same period it increased significantly at Copargo- Centre, and decreased at Pabégou.The average cost per malaria case prevented (CE) was respectively 85,572.4 FCFA at Copargo Centre, 38,932.6 FCFA at Kouandé Centre, 15,940.6 FCFA at Pabégou and 174,728.5 FCFA at Guilmaro. According to the results, the CE ratio at Kouandé-Centre is lower than the CE ratio at Copargo- Centre and the CE ratio at Guilmaro is higher than the CE ratio at Pabégou.The LLINs?+?IRS strategy is more cost effective in urban areas than the LLINs-only strategy. The opposite result is observed in rural areas.

Conclusion

The LLINs?+?IRS strategy is cost effective in highly endemic areas both urban and rural, if communities sleep in sprayed structures and use LLINs even when it is hot.
  相似文献   

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