Assessment of PCBs and Hydroxylated PCBs as Potential Xenoestrogens: In Vitro Studies Based on MCF-7 Cell Proliferation and Induction of Vitellogenin in Primary Culture of Rainbow Trout Hepatocytes

In the present study, four structurally diverse polychlorinated biphenyls (PCBs) were chosen from a set of 20 PCBs selected to represent the 154 tetra- through hepta-chlorinated biphenyls. The purpose was to determine estrogenic activities of the chosen PCBs and five of their hydroxylated derivatives (OH-PCBs). A human breast cancer cell line (MCF-7) and primary cultures of rainbow trout (Oncorhyncus mykiss) hepatocytes were used to determine estrogenic effects. The PCBs 2,2′,4,6,6′-pentachlorobiphenyl (104) and 2,2′,3,4′, 5,6,6′-heptachlorobiphenyl (188), and the hydroxylated PCBs 2,2′,4′,6′-tetrachloro-4-biphenylol (4′-50), 2′,4′,6′-trichloro-4-biphenylol (4′-30), 2′,3,5,5′-tetrachloro-4-biphenylol (4′-72), 2′,3,3′,5′,6′-pentachloro-4-biphenylol (4′-112), and 2′,3,4′,5,6′-pentachloro-4-biphenylol (4′-121) significantly increased MCF-7 cell proliferation. The coaddition of hydroxytamoxifen, an estrogen antagonist, inhibited increased cell proliferation. The activity of the hydroxylated PCBs 4′-50 and 4′-30 was significantly higher at all nominal concentrations tested as compared to the corresponding PCB, viz., PCB 104. The hydroxylated PCBs 4′-50, 4′-30, 4′-72 and 4′-112 induced vitellogenin synthesis in rainbow trout hepatocytes. Significant differences were found in the MCF-7 system between the parent PCB and its hydroxylated derivative, viz., for 4′-50/4′-30 and 104, and in the rainbow trout hepatocyte assay between 4′-112 and 112, respectively. No activity was observed for PCB 58 in any of the two assays in the present study. Even though cells from two different species (human and fish) are used in the present study, the results obtained by the two methods agree fairly well. In both studies the hydroxylated PCBs were more active than the PCBs, and 4′-30 was the most active compound second only to 17β-estradiol. Received: 28 August 1998/Accepted: 3 March 1999     

Errata

In the Lucas Lecture 1981, ‘Professional Ethics—ForWhose Benefit’, by Paul Sieghart (32, 4–14) the following errors occurred. The author's position is Barrister not Barrister-at-Law. The following lines should read: p. 4, column 2, line 2: ‘troubled Dr Conor Cruise O'Brien(1980).’ p. 5, column 1, line 32: ‘regard it as the study of morality,that is, the’. p. 9, column 1, line 27: ‘conflicts? Of all the specialties,that of. p. 9, column 2, line 4: ‘order of a competent court ortribunal’. p. 12, column 2, line 16: ‘himself of that obligationbecause another’.     

Wastewater disinfection and organic matter removal using ferrate (VI) oxidation

The use of iron in a +6 valence state, (Fe (VI), as FeO₄^-2) was tested as a novel alternative for wastewater disinfection and decontamination. The removal of organic matter (OM) and index microorganisms present in an effluent of a wastewater plant was determined using FeO₄^-2 without any pH adjustment. It was observed that concentrations of FeO₄^-2 ranging between 5 and 14 mg l^-1 inactivated up to 4-log of the index microorganisms (initial concentration c.a. 10⁶ CFU/100 ml) and achieved OM removal up to almost 50%. The performance of FeO₄^-2 was compared with OM oxidation and disinfection using hypochlorite. It was observed that hypochlorite was less effective in OM oxidation and coliform inactivation than ferrate. Results of this work suggest that FeO₄^-2 could be an interesting oxidant able to deactivate pathogenic microorganisms in water with high OM content and readily oxidize organic matter without jeopardizing its efficiency on microorganism inactivation.     

Fate of Chlortetracycline in Korean Arable Soil

The widespread use of the pharmaceutical chlortetracycline to treat human and animal infectious diseases is raising concern in Korea regarding the potential development of antibiotic-resistant bacteria. This study investigated the fate of chlortetracycline in Korean arable soils, to assess its environmental impact. The estimated half-life of chlortetracycline was 26.70–27.17 days indoors and 18.63–30.16 days outdoors. The chlortetracycline epimers and metabolites, 4-epichlortetracycline and 4-epi-anydrochlotetracycline were determined using liquid chromatography tandem mass spectroscopy. The respective concentrations of 4-epi-anydrochlotetracycline and 4-epichlortetracycline were 1.91%–9.71% and 11.12%–23.92% of the total chlortetracycline residual concentration indoors and 2.96%–11.44% and 17.61%–40.73% outdoors.     

Diets containing the highest levels of dairy products are associated with greater eutrophication potential but higher nutrient intakes and lower financial cost in the United Kingdom

Previously, the nutritional contribution, environmental and financial costs of dairy products have been examined independently. Our aim was to determine the nutritional adequacy, financial cost and environmental impact of UK diets according to dairy content. In this cross-sectional study of adults (19–64 years) from the UK National Diet and Nutrition Survey years 1–4 (n = 1655), dietary intakes assessed from 4-day estimated food diaries were organized into quartiles (Q) total grams of dairy (milk, cheese, yogurt, dairy desserts) and analyzed using ANCOVA controlling for age, sex and energy intake with Bonferroni post hoc test for nutritional adequacy, Alternative Healthy Eating Index (AHEI-2010), environmental impact [greenhouse gas emissions (GHGE), eutrophication and acidification potentials], financial cost, markers of health and cardio-metabolic diseases. Nutritional adequacy, particularly for protein, calcium and iodine (+ 18 g, + 533 mg, + 95 g, respectively, all P < 0.0001) and AHEI-2010 (P < 0.0001) were significantly higher and systolic BP (− 2 mmHg, P = 0.019) was significantly lower for the higher-dairy diets (Q4, 274–1429 g/day dairy), compared with diets containing lower dairy (Q1, 0–96 g/day dairy). Diets in Q4 had lower financial cost (− 19%, P < 0.0001) and the greatest eutrophication potential, compared with Q1 (+ 29%, P < 0.0001). Yet the environmental (GHGE) and financial costs per unit nutrient (riboflavin, zinc, iodine, magnesium, calcium, potassium) were lower in Q4 than Q1 (all P < 0.0001). Diets with the highest dairy content had higher nutrient composition, better diet quality, were associated with lower BP and financial cost, but with higher eutrophication potential. Robust environmental data for many of food groups are limited and this needs an urgent addressing. This trial was registered on clinicaltrials.gov as NCT03407248.     

Previous Breastfeeding Practices and Duration of Exclusive Breastfeeding in the United States

We examined the influence of duration of exclusive breastfeeding (DEBF) for a mother’s earlier children on the DEBF for her later children among multiparous women from the 2002 National Survey of Family Growth. DEBF was categorized as: never breastfed (NBF) (referent); not exclusively breastfed or exclusively breastfed for <4 months (EBF < 4); and exclusively breastfed for ≥4 months (EBF ≥ 4). We examined DEBF using weighted percentages and odds ratios (OR) with 95% confidence intervals (CI) from multinomial logistic regression models, adjusting for maternal factors. About 70% of multiparous women (n = 2,149) repeated the duration of exclusive breastfeeding of their first child for their second child; 14% of women repeated EBF ≥ 4. Among multiparous women, the adjusted odds ratio for EBF ≥ 4 for second children was 7.2 (95% CI = 4.0–12.9) when first children were EBF < 4 and 90.7 (95% CI = 45.4–181.4) when first children were EBF ≥ 4, relative to NBF first children. In analyses where DEBF of third children was the outcome, odds of EBF ≥ 4 were more strongly influenced by DEBF of second children while the impact of DEBF of first children was not as strong. Older maternal age and being married were related to an increased DEBF. Being married at second birth predicted a change from NBF for first children to EBF ≥ 4 for second children (OR = 6.2, 95% CI = 2.7–14.2). In conclusion, mothers generally repeated the DEBF of their previous child. For third children, DEBF of the second child was more likely to be repeated than that of the first child.     

A Multi-Level Assessment of a Program to Teach Medical Students to Teach

Few longitudinal programs exist to teach senior students (MS4s) to be teachers, nor have there been any reports of comprehensive program evaluation in this area. The primary objectives of this study were to describe our ongoing faculty development effort and to develop a multi-level program evaluation, using Dixon’s model. The TALKS (Teaching and Learning Communication Skills) program is a senior elective and open to all MS4s. We evaluated our program through assessment of its participants at three levels: level 1, opinion; level 2, competence; and level 3, performance; but not level 4, patient outcomes. The authors used a retrospective, pre–post questionnaire to assess MS4 attitudes about their educational experiences, a traditional instrument to assess their teaching, an interaction analysis technique using Bloom’s taxonomy to assess MS4s’ feedback skills, and a SP exam to assess MS4 communication skills. The authors hypothesized that MS4s participating in TALKS would view medical education more positively and informatively, would demonstrate important principles in giving feedback, would be assessed as excellent teachers, and would perform better than controls in an SP exam emphasizing communication skills. Results revealed that MS4s’ ratings as teachers were very good to excellent, with the highest scores on the items “knowledgeable, supportive of me, and answering questions clearly.” (Level 1, Opinion) MS4s’ perceptions of their knowledge, attitudes and skills increased significantly from the pre to the post-questionnaire. (Level 2, Competence) MS4 feedback skills to MS2s revealed they did more talking than ideal, often at the lowest levels of Bloom’s taxonomy. (Level 3, Performance) MS4s demonstrated better communication skills than controls on an evaluation by professional SPs. (Level 3, Performance).     

Determinants of Polychlorinated Biphenyl Levels in Plasma from 42-Month-Old Children

We report on the PCB levels in plasma from 42-month-old children and the factors that determine these levels. We measured the levels of the PCB congeners 118 (2,4,5-3′4′ pentachlorobiphenyl (CB)), 138 (2,3,4-2′4′5′hexaCB), 153 (2,4,5-2′4′5′hexaCB), and 180 (2,3,4,5-2′4′5′heptaCB) in cord plasma, breast milk, and plasma from 42-month-old children (n = 126) living in the Groningen area, The Netherlands. The sum of the levels of these four congeners was calculated for cord plasma (ΣPCB_cord), breast milk (ΣPCB_milk), and 42-month plasma (ΣPCB_42mo). ΣPCB_cord was used as a measure of prenatal exposure. Postnatal exposure was assessed in terms of the ΣPCB_milk and the duration of lactation. In addition, maternal factors including age, body weight and height, parity, and formal education were recorded. In 42-month-old children who have been fully breast-fed for at least six weeks as babies, the median ΣPCB_42mo was 4.5 times as high as that in formula-fed children (0.81 μg/L vs. 0.18 μg/L). The PCB levels in cord blood and human milk and the duration of breast-feeding predict the plasma PCB level at 42 months. Each additional week of full breast-feeding is estimated to result in an increase of 0.3% of the milk PCB level. We concluded that lactation is a major source for the child's PCB body burden at 42 months. Received: 24 July 1997/Accepted: 22 December 1997     

Antimicrobial susceptibilities of <Emphasis Type="Italic">Campylobacter jejuni</Emphasis> isolates from hospitalized children in Athens,Greece, collected during 2004–2005

A total of 170 Campylobacter jejuni strains isolated from the stool of children with clinical gastroenteritis, aged from 3 months to 14 years, were collected during a two-year period (2004–2005). From the 170 strains 30% were resistant to ciprofloxacin (MIC ≥ 4 μg/ml), 55% to tetracycline (MIC > 8 μg/ml), 13% to clindamycin (MIC ≥ 8 μg/ml), 4% to ampicillin (MIC > 16 μg/ml), 6% to erythromycin (MIC ≥ 8 μg/ml), 4% to coamoxiclav (MIC ≥ 16/8 μg/ml) and 0% to gentamicin. Compared to previous reports from Greece, the antimicrobial resistance rates to erythromycin, ampicillin and coamoxiclav remain low, while they are still high for tetracycline and ciprofloxacin. Considering similar reports from many other countries and the high incidence of Campylobacter gastroenteritis worldwide, the value of ciprofloxacin as a first choice drug␣in the empiric treatment of the infection is questionable.     

Chronic bronchitis and pesticide exposure: a case–control study in Lebanon

Objective Pesticides are widely used toxics. The objective of the study is to evaluate the odds of exposure to pesticides in chronic bronchitis patients.Methods Using the American Thoracic Society standardized questionnaire confirmed by medical diagnosis of chronic bronchitis, a case–control study was␣performed in Lebanon. Pesticide exposure was estimated and between groups comparison was made.Results The study involved 262 controls and 110 chronic bronchitis outpatient subjects from 10 medical centers. Any exposure to pesticides was associated to chronic bronchitis (OR = 2.46 [1.53–3.94]; p < 10⁻⁴). Occupational use presented the highest association (15.92 [3.50–72.41]; p < 10⁻⁴), followed by regional exposure (3.70 [2.05–6.70]; p < 10⁻⁴). Results were confirmed by multivariate and subgroup analysis.Conclusion Pesticide exposure was associated with chronic bronchitis in Lebanese adults. Pesticides toxicological effects may explain chronic respiratory effects associations found with all exposure types.     

Evaluation of pot-chlorination of wells during a cholera outbreak, Bissau, Guinea-Bissau, 2008

We evaluated the ability of UNICEF-designed pot-chlorinators to achieve recommended free residual chlorine (FRC) levels in well water in Bissau, Guinea-Bissau, during a cholera outbreak. Thirty wells were randomly selected from six neighbourhoods. Pot-chlorinators – perforated plastic bottles filled with gravel, sand and calcium hypochlorite granules – were placed in each well. FRC was measured before and 24, 48 and 72 h after placement and compared with World Health Organization (WHO)-recommended levels of 1 mg L^-1 for well water during cholera outbreaks and 0.2–5 mg L^-1 in non-outbreak settings. Presence of well covers, distance from wells to latrines, and rainfall were noted. Complete post-chlorination data were collected from 26 wells. At baseline, no wells had FRC >0.09 mg L^-1. At 24, 48 and 72 h post-chlorination, 4 (15%), 1 (4%) and 0 wells had FRC 1 mg L^-1 and 16 (62%), 4 (15%) and 1 (4%) wells had FRC between 0.2 and 5 mg L^-1, respectively. Several families reported discontinuing household water chlorination after wells were treated with pot-chlorinators. Pot-chlorinators failed to achieve WHO-recommended FRC levels in well water during a cholera outbreak, and conveyed a false sense of security to local residents. Pot-chlorination should be discouraged and alternative approaches to well-water disinfection promoted.     

Inactivation of Nitrosomonas europaea and pathogenic Escherichia coli by chlorine and monochloramine

The purpose of this study was to measure the chlorine and monochloramine inactivation kinetics of Nitrosomonas europaea at 21°C in the presence and absence of particles. The inactivation kinetics rates were compared with those obtained with Escherichia coli O157:H7. The results show that, in pure water, the use of free chlorine produced 4 log₁₀ of N. europaea inactivation at a CT value of 0.8 mg.min l^-1, whereas monochloramine yielded 4 log₁₀ of inactivation at CT values of approximately 9.9–16.4 mg.min l^-1. With E. coli, chlorine produced approximately 4 log₁₀ of inactivation at a CT of 0.13 mg.min l^-1, whereas monochloramine resulted in 4 log₁₀ of inactivation at a CT of approximately 9.2 mg.min l^-1. These results suggest that N. europaea is more resistant to monochloramine and chlorine than E. coli. Corrosion debris, soil material and wastewater had no statistically significant (p < 0.05) impact on the inactivation of N. europaea by either chlorine or monochloramine. It seems likely that the CT values present in distribution systems would be sufficient to control suspended cells of these two organisms, especially under conditions of breakpoint chlorination, which could be used to control nitrification. Adequate disinfection should prevent the growth of these organisms in a distribution system.     

Air Quality Status During Diwali Festival of India: A Case Study

The PM_2.5 and PM₁₀ samples were collected during Diwali celebration from study area and characterized for ionic concentration of four anions (NO₃ ⁻, NO₂ ⁻, Cl⁻, SO₄ ²⁻) and five cations (K⁺, Mg²⁺, NH₄ ⁺, Ca²⁺, Na⁺). The results showed that the ionic concentrations were three times compared to those on pre and post Diwali days. Predominant ions for PM_2.5 were K⁺ 33.7 μg/m³, Mg⁺ 31.6 μg/m³, SO₄ ²⁻ 22.1 μg/m³, NH₄ ⁺ 17.5 μg/m³ and NO₃ ⁻ 18 μg/m³ and for PM₁₀ the ionic concentrations were Mg⁺ 29.6 μg/m³, K⁺ 26 μg/m³, SO₄ ²⁻ 19.9 μg/m³, NH₄ ⁺ 16.8 μg/m³ and NO₃ ⁻ 16 μg/m³. While concentration of SO₂ and NO₂ were 17.23, 70.33 μg/m³ respectively.     

Human toxicokinetics of inhaled monochlorobenzene: latest experimental findings regarding re-evaluation of the biological tolerance value

Objective: The aim of this study was to obtain toxicokinetic data on the absorption and elimination of monochlorobenzene (MCB) in blood and its main metabolite 4-chlorocatechol (4-ClCat) as well as on the isomeric chlorophenols (o-ClPh, m-ClPh, and especially p-ClPh as the main ClPh metabolite) in urine for re-evaluation of the biological tolerance (BAT) value of MCB. Methods: Eight subjects performed 8-h inhalation tests daily over five successive days in an exposure chamber, at a maximum allowable concentration at the workplace (MAK) value of 10 ppm MCB. Five and two probands carried out the test series during physical activity levels of 75 and 50 W, respectively, for 10 min/h on a bicycle ergometer, and one subject was exposed continuously while at rest. MCB and its metabolites were analyzed by gas chromatography in combination with mass spectrometry. Results: The mean MCB blood concentration of the five subjects exposed during physical activity of 75 W was 217 ± 42 μg/l. The relationship of the mean blood concentration measured under the conditions of rest or 50 and 75 W activity levels was in a ratio of about 1:1.7:2.8. The half-life values in the first hour after ending the exposures were 53 min and 150 min for the ensuing period, with steady-state being reached after 45 min. The mean 4-ClCat concentration in urine at the end of the five days was 150 ± 13 mg/g creatinine in the case of the subjects exposed at 75 W, which decreased to 25 mg/g creatinine at the beginning of the next exposure. The analogous p-ClPh concentrations were 25 ± 2 and 9 ± 2 mg/g creatinine. The elimination half-life values of the ClPh isomers ranged from 12.4 to 16.5 h, and the half-life of 4-ClCat was 6.4 h. There was no apparent tendency for MCB and its metabolites to accumulate in blood or urine. Conclusions: The results are in accordance with relevant field and laboratory studies. Taken into consideration with the 95th percentile, the evaluated BAT values should be set at levels of 300 μg MCB/l blood, 175 mg 4-ClCat/g creatinine or alternatively at 30 mg p-ClPh/g creatinine in urine after the end of a shift. At the beginning of the next shift, the BAT values of the metabolites should be 35 and 15 mg/g creatinine, respectively. Received: 20 December 1999 / Accepted: 25 April 2000     

Validation Study of a Distress Screener

Objectives A 3-item screening instrument called the Distress Screener was developed for early identification of distress among employees on sick leave. The Distress Screener consists of three items obtained from the distress subscale of the four-dimensional symptom questionnaire (4DSQ). This study assessed an optimal cut-off point and validated the Distress Screener by relating it to the 4DSQ and to medical diagnoses. Methods 171 sick-listed employees filled in the Distress Screener and the 4DSQ (containing four subscales: distress, depression, anxiety and somatisation) and medical diagnoses were obtained from occupational physicians (OPs). The optimal cut-off point was assessed by computing sensitivity and specificity values. Validity was assessed by relating the Distress Screener score to the scores on 4DSQ subscales. In addition scores were compared to mental health medical diagnoses and the degree of similarity between two repeated measurements was obtained. Results Using the 4DSQ distress score >10 as reference standard, the optimal cut-off point of the Distress Screener was ≥4. Regarding validity, a high correlation (0.82) existed between the Distress Screener and the 4DSQ distress subscale and it was significantly different from the correlations with the other 4DSQ subscales. Also a high correlation existed for the test–retest reliability (0.83). Furthermore, a high score on the Distress Screener seemed to be related to the medical diagnosis ‘Stress-related complaints’. All low scores seemed to be related to the medical diagnosis ‘Other complaints’. Sensitivity (0.85) and specificity (0.78) values, and positive and negative predictive values of the screener were comparable to those of the 4DSQ distress subscale. Conclusions The Distress Screener is a valid instrument for use by the OP during consulting time as a quick scan for early identification of distress in employees on sick leave. The cut-off point ≥4 is useful for early identification of distress in employees on sick leave.     

Influence of gender on DHA synthesis: the response of rat liver to low dietary α-linolenic acid evidences higher ω3 ∆4-desaturation index in females

Purpose  

The conversion rate of α-linolenic acid (ALA) into docosahexaenoic acid (DHA) is determined by dietary and non-dietary factors. Higher capacity of DHA synthesis has been evidenced in females, indicating that sex factors influence the conversion pathway. To evaluate the extent to which sexual dimorphism of DHA synthesis is subordinated to nutritional handling, we measured the ω3 ∆4-desaturation index in male and female rats receiving adequate or inadequate amounts of ALA. The ω3 ∆4-desaturation index was drawn from the DHA to docosapentaenoic acid (ω3DPA) ratio in liver phospholipids.     

Comparative Antioxidant Profiling of Tolerant and Sensitive Varieties of Brassica juncea L. to Arsenate and Arsenite Exposure

Comparative antioxidant profiling of tolerant (TPM-1) and sensitive (TM-4) variety of Brassica juncea L. was performed after exposure to arsenate [As(V)] and arsenite [As(III)]. TPM-1 demonstrated higher accumulation of As upon exposure to both 500 μM As(V) and 250 μM As(III) (49 and 37 μg g⁻¹ dw after 15 days) as compared with that observed in TM-4. The activities of various antioxidant enzymes and the level of glutathione and proline demonstrated, in general, a comparatively better response in TPM-1 than in TM-4 that presumably allowed TPM-1 to tolerate higher As concentrations as compared with that of TM-4.     

Patterns of antibody response in humans to the anthrax vaccine adsorbed (AVA) primary (six-dose) series

The antibody profile during and after the six-dose primary vaccination series with anthrax vaccine adsorbed (AVA, Biothrax) was characterized in 86 human volunteers. Ninety-three percent of recipients developed IgG antibodies to Bacillus anthracis protective antigen (PA) after two doses, and 100% were seropositive after dose #3. Geometric mean concentrations (GMC) of IgG to PA measured before and after each dose were significantly lower after injection #3 (peak GMC=146.65 microg/mL, trough GMC=15.16 microg/mL) than after injections #4 (peak GMC=430.46 microg/mL, trough GMC=94.57 microg/mL), #5 (peak GMC=415.05 microg/mL, trough GMC=81.94 microg/mL), or #6 (peak GMC=401.16 microg/mL, trough GMC=96.19 microg/mL) (por=0.7923 for each). Decay rates for IgG to PA were significantly faster after injection #3 (half life [T1/2]=39.21 days) than after injections #4 (T1/2=72.03 days), #5 (T1/2=70.14 days), and #6 (T1/2=74.59 days) (p相似文献