Effects of 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) injected into the yolks of chicken (Gallus domesticus) eggs prior to incubation

The yolks of White Leghorn chicken (Gallus domesticus) eggs were injected prior to incubation with either 3,3,4,4,5- pentachlorobiphenyl (PCB 126) at doses ranging from 0.1 to 12.8 g/kg egg or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at doses ranging from 0.04 to 0.64 g/kg egg. Chicks were subjected to necropsy within 24 h of hatching. The brain, bursa, heart, liver, and spleen were removed and weighed. Assessment of the rate of hatching indicated an LD₅₀±S.E. of 2.3±0.19 g/kg egg (7.1±0.58 nmol/kg egg) for PCB 126 and 0.15±0.012 g/kg egg (0.47±0.037 nmol/kg egg) for TCDD. No significant differences in the incidence of developmental abnormalities (structural defects and edema) were observed in TCDD-exposed embryos, while PCB 126 caused significantly more developmental abnormalities at 3.2, 6.4, and 12.8 g/kg egg than the vehicle control. PCB 126 caused lower hatchling weights and greater relative brain, heart, and liver weights when compared to the vehicle control group at a dose of 3.2 g/kg egg which is greater than the LD₅₀. TCDD at 0.08 g/kg egg caused relative bursa weights to be less than those of the vehicle control. A toxic equivalency factor (TEF) of 0.07 was determined for PCB 126 in relation to TCDD based on overt lethality.     

Tissue Distribution of Methylsulfonyl Metabolites Derived from 2,2′,4,5,5′-Penta- and 2,2′,3,4′,5′,6-Hexachlorobiphenyls in Rats

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     

Occurrence of Selected Polybrominated Diphenyl Ethers and 2,2′,4,4′,5,5′-Hexabromobiphenyl (BB-153) in Sewage Sludge and Effluent Samples of a Wastewater-Treatment Plant in Cape Town,South Africa

The reuse of treated effluent from wastewater treatment plants (WWTPs) as alternative water source for sport-field or landscape irrigation, agricultural, and other industrial purposes is growing significantly. Similarly, the application of treated sludge (biosolid) to agricultural soils is now being considered globally as the most economic means of sludge disposal. However, the presence of emerging organic contaminants in these matrices, including polybrominated diphenyl ethers (PBDEs), which are potential endocrine disruptors, portends a high health risk to humans and the environment in general. In this study, effluent and sewage sludge samples collected from a WWTP were analysed for some selected PBDE congeners (BDE congeners 28, 47, 99 100 153 154 183, and 209) as well as BB-153 using a high-capillary gas chromatograph equipped with an electron capture detector. The sum of the eight PBDE congeners ranged from 369 to 4370, 19.2 to 2640, and 90.4 to 15,100 ng/l for raw water, secondary effluent, and final effluent, respectively. A similar result was observed for sewage sludge samples, which ranged between 13.1 and 652 ng/g dry weight (dw). The results obtained for BB-153 were generally lower compared with those found for most PBDE congeners. These ranged from ND to 18.4 ng/l and ND to 9.97 ng/g dw for effluents and sewage sludge, respectively. In both matrices, BDE 47 and 209 congeners were found to contribute significantly to the overall sum of PBDEs. The reuse of the treated effluent, particularly for agricultural purposes, could enhance the possibility of these contaminants entering into the food chain, thus causing undesirable health problems in exposed subjects.     

Chronic toxicity and bioaccumulation of 2,5,2′,5′- and 3,4,3′,4′-tetrachlorobiphenyl and Aroclor® 1242 in the amphipodHyalella azteca

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.     

Short-Term Distribution, Metabolism, and Excretion of 2,2′,5-Tri-, 2,2′,4,4′-Tetra-, and 3,3′,4,4′-Tetrachlorobiphenyls in Prepubertal Rats

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     

Enantiomeric Enrichment of 2,2′,3,3′,6,6′-Hexachlorobiphenyl (PCB 136) in Mice After Induction of CYP Enzymes

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.     

Toxicities of 2,2′,4,4′- and 3,3′,4,4′-tetrachlorobiphenyls to house flies at different ages and enzyme levels

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.     

Embryotoxicity of 3,3′,4,4′-tetrachloroazobenzene and 3,3′,4,4′-tetrachioroazoxybenzene in the chick embryo

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.     

Effects of a Branched <Emphasis Type="Italic">p</Emphasis>-Nonylphenol Isomer (4(3′,6′-dimethyl-3′-heptyl)-phenol) on Embryogenesis in <Emphasis Type="Italic">Lymnae stagnalis</Emphasis> L.

The tertiary branched alkyl-chain isomers of p-nonylphenol (NP) are perceived to have more estrogenic potency than its constituent secondary and primary straight alkyl-chain isomers. Investigations with single tertiary branched isomers of NP can therefore contribute toward the elucidation of the mechanisms of toxicity and estrogenicity of NP. A single tertiary branched alkyl-chain isomer (4(3′,6′-dimethyl-3′-heptyl)-phenol) was used in studies to determine its effects on embryonic growth and mortality in Lymnaea stagnalis L. Egg masses were exposed to the test compound for 20 days in a static waterborne-exposure regime with an average NP concentration of 105 μg/L and water temperature range of 18–20°C. Observations were made under a microscope and pictures were taken with a digital camera to determine the various developmental stages of growth, the duration of growth in each stage, embryo hatchability, and embryo mortality. The isomer was found to cause significant delay in all stages of growth and more significantly in the Morula and Veliger stages. An increase in embryo mortality, from the third day until the end of the experiment, was observed in exposed egg masses compared to controls. The hatching success of embryos was also significantly reduced by exposure, with 81% hatchability in exposed egg masses compared to 93% in the controls, after 18 days of continuous exposure. The encapsulating jelly strand that completely covers the rows of egg masses may have prevented the isomer residues from effectively penetrating into the embryos as shown by the observed low bioconcentration factors of the isomer in egg masses during exposure, resulting in unexpectedly lower observed estrogenic effects. However, this factor was not investigated. In vivo biotransformation of some of the residues of the isomer into catechol metabolites by the embryos during exposure could also result in the reduction of its estrogenic potential. To understand more fully the extent of toxicity and estrogenicity of this isomer, in vitro estrogenic assays are recommended. It would also be necessary to investigate its estrogenic effects on embryo development after in vivo maternal exposure.     

Children’s and Parents’ Marburg Sugar Index (MSI) Values: Are They Comparable?

Studies on children’s nutritional behaviour (CNB) rarely compare children’s answers regarding the frequency of their sugar intake with the respective statements of their parents. Therefore, data from a prevention study were used to analyse this aspect, as well as a potential correlation between Marburg Sugar Index (MSI) values and caries experience of children. The present study based its questionnaire data on CNB and caries data. Pairs of questionnaires filled in separately by children and parents of the participating families were dichotomised by either having completed the diet section entirely (Group A) or in part (Group B). The MSI scores were calculated separately for children and parents. The statistical confidence level was set at α = 0.05 (two-sided). Furthermore, the Pearson correlation coefficient was calculated and tested for “r = 0”. Additionally, a test for equality of the correlations was applied. The number of available questionnaire pairs was 429 in Group A and 400 in Group B. In both groups, significant correlations between children’s and parents’ MSI scores (A: r = 0.301, p < 0.001; B: r = 0.226, p < 0.001) were found. Using Spearman’s Rho, a significant correlation between MSI scores and children’s caries experiences was observed in Group A. MSI scores based on dietary questionnaires can be used to obtain consistent information on children’s CNB provided by the children themselves or their parents. This is true even when the MSI score has to be calculated on the basis of incomplete questionnaires. Questionnaire-based CNB information can improve the effectiveness of individual or group preventive measures supplemented by individually adapted nutritional counselling.     

Cyclic 3′, 5′-adenosine monophosphate and cyclic 3′, 5′-guanosine monophosphate metabolism in malnutrition

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.     

Seasonal and nocturnal domiciliary human landing/biting behaviour of Lutzomyia (Lutzomyia) evansi and Lutzomyia (Psychodopygus) panamensis (Diptera; Psychodidae) in a periurban area of a city on the Caribbean coast of eastern Venezuela (Barcelona; Anzoátegui State)

In recent years, in addition to American cutaneous leishmaniasis (ACL), a significant number of cases of American visceral leishmaniasis (AVL) have been reported in periurban areas of Barcelona city (Anzoátegui State, Venezuela). We studied the bionomics of Lutzomyia (Lutzomyia) evansi and Lutzomyia (Psychodopygus) panamensis, possible vectors of AVL and ACL, respectively, in El Rincón, a periurban village of that city. To evaluate the seasonal domiciliary landing/biting activity of sandflies on human bait, a house was chosen in El Rincón. Landing catches were carried out between 18:00 and 06:00, once a month for a year. The results show the presence of 2 species, Lu. (Lu.) evansi (89.9%) and Lu. (Psy.) panamensis (10.1%). Lu. evansi was most abundant in the months of October and July, associated with the bimodal cycle of annual rainfall in the area. Maximum landing/biting activity of Lu. evansi was observed at 24:00 and 03:00. These findings suggest that at this time of the year and at these hours there is heightened risk of the transmission of AVL. Lu. panamensis monthly abundance also shows a direct association with rainfall and maximum landing/biting activity was observed between 02:00 and 03:00. The lower domiciliary abundance of Lu. panamensis suggests its greater importance in the extradomiciliary transmission of ACL.     

主动"维修"你的老公(下)

婚后生活鸡零狗碎，热战频频、冷战不断，其实。聪明的妻子为何不早早预备好一套“维修”老公的？“玫瑰秘籍”呢？要化干戈为玉帛，做妻子的就要坚持积极改善，主动“维修”的理念。谁让“好女人是一所学校”呢！     

The Health Utilities Index (HUI<Superscript>®</Superscript>): concepts,measurement properties and applications

This is a review of the Health Utilities Index (HUI^®) multi-attribute health-status classification systems, and single- and multi-attribute utility scoring systems. HUI refers to both HUI Mark 2 (HUI2) and HUI Mark 3 (HUI3) instruments. The classification systems provide compact but comprehensive frameworks within which to describe health status. The multi-attribute utility functions provide all the information required to calculate single-summary scores of health-related quality of life (HRQL) for each health state defined by the classification systems. The use of HUI in clinical studies for a wide variety of conditions in a large number of countries is illustrated. HUI provides comprehensive, reliable, responsive and valid measures of health status and HRQL for subjects in clinical studies. Utility scores of overall HRQL for patients are also used in cost-utility and cost-effectiveness analyses. Population norm data are available from numerous large general population surveys. The widespread use of HUI facilitates the interpretation of results and permits comparisons of disease and treatment outcomes, and comparisons of long-term sequelae at the local, national and international levels.     

Measurement equivalence of the Consumer Assessment of Healthcare Providers and Systems (CAHPS<Superscript>®</Superscript>) Medicare survey items between Whites and Asians

Purpose

Asians report worse experiences with care than Whites. This could be due to true differences in care received, expectations about care, or survey response styles. We examined responses to the Consumer Assessment of Healthcare Providers and Systems (CAHPS^®) Medicare survey items by Whites and Asians, controlling for underlying level on the CAHPS constructs.

Methods

We conducted multiple group analyses to evaluate measurement equivalence of CAHPS Medicare survey data between White and Asian Medicare beneficiaries for CAHPS reporting composites (communication with personal doctor, access to care, plan customer service) and global ratings of care using pooled data from 2007 to 2011. Responses were obtained from 1,326,410 non-Hispanic Whites and 40,672 non-Hispanic Asians (hereafter referred to as Whites and Asians). The median age for Whites was 70, with 24 % 80 or older, and 70 for Asians, with 23 % 80 or older. Fifty-eight percent of Whites and 56 % of Asians were female.

Results

A model without group-specific estimates fit the data as well as a model that included 12 group-specific estimates (7 factor loadings, 3 measured variable errors, and 2 item intercepts): Comparative Fit Index = 0.947 and 0.948; root-mean-square error of approximation = 0.052 and 0.052, respectively). Differences in latent CAHPS score means between Whites and Hispanics estimated from the two models were similar, differing by 0.053 SD or less.

Conclusions

This study provides support for measurement equivalence of the CAHPS Medicare survey composites (communication, access, customer service) and global ratings between White and Asian respondents, supporting comparisons of care experiences between the two groups.

     

Biological Activity and Physicochemical Parameters of Marine Halogenated Natural Products 2,3,3′,4,4′,5,5′-Heptachloro-1′-Methyl-1,2′-Bipyrrole and2,4,6-Tribromoanisole

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 (S_w,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.