Serum and follicular fluid organochlorine concentrations among women undergoing assisted reproduction technologies

<p>Abstract</p> <p>Background</p> <p>Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, is widespread among the general population. There is evidence of adverse effects on reproduction and early pregnancy in relation to organochlorine exposure but human studies remain limited. The increased use of assisted reproductive technologies (ART) presents unique opportunities for the assessment of environmental influences on early pregnancy outcomes not otherwise observable in humans, but studies need to be designed to maximize the efficiency of the exposure data collected while minimizing exposure measurement error.</p> <p>Methods</p> <p>The present study was conducted to assess the correlation between concentrations of organochlorines in serum and follicular fluid samples collected from a subset of women undergoing ART in a large study that took place between 1994 and 2003, as well as the temporal reliability of serum organochlorine concentrations among women undergoing multiple ART cycles in the study. PCB congeners (118, 138, 153, and 180), 1,1,1-trichloro-2,2-bis(<it>p</it>-chlorophenyl)ethane (p,p'-DDT), the DDT metabolite p,p'-DDE, hexachlorobenzene (HCB), oxychlordane, trans-nonachlor and mirex were measured in 72 follicular fluid samples and 265 serum samples collected from 110 women.</p> <p>Results</p> <p>Organochlorine concentrations in paired serum and follicular fluid samples were correlated, with Pearson and Spearman coefficients ranging from 0.60 to 0.92. Serum organochlorine concentrations were two- to three-fold greater than in follicular fluid, and a significant inverse trend was observed in the distribution of follicular fluid:serum ratios with increasing molecular weight of the compound (p-value for trend < 0.0001). Serum organochlorine concentrations were highly reliable over the course of several months, with intraclass correlation coefficients ranging from 0.86 to 0.98. Finally, there was evidence for a declining trend in organochlorine concentrations between samples collected between years 1994–1998 and those collected in 1999–2003.</p> <p>Conclusion</p> <p>Our results support the use of a single serum sample to adequately represent a more biologically relevant dose (concentrations in follicular fluid), as well as exposure levels over time, in epidemiological studies of ART outcomes in relation to organochlorine exposure.</p

Toenails as biomarker of exposure to essential trace metals: A review

Health problems associated with essential trace metals can result from both inadequate (i.e., low intake) and excessive exposures (i.e., from environmental and/or occupational source). Thus, measuring the exposure level is a real challenge for epidemiologists. Among non-invasive biomarkers that intend to measure long-term exposure to essential trace metals, the toenail is probably the biological matrix with the greatest potential. This systematic review collects the current evidence regarding the validity of toenail clippings as exposure biomarker for trace metals such as boron, cobalt, copper, iron, manganese, molybdenum, selenium, silicon, vanadium and zinc. Special attention was paid to the time-window of exposure reflected by the toenail, the intraindividual variability in exposure levels over time in this matrix, and the relationship of toenail with other biomarkers, personal characteristics and environmental sources. Our search identified 139 papers, with selenium and zinc being the most studied elements. The variability among studies suggests that toenail levels may reflect different degrees of exposure and probably correspond to exposures occurred 3–12 months before sampling (i.e., for manganese/selenium). Few studies assessed the reproducibility of results over time and, for samples obtained 1–6 years apart, the correlation coefficient were between 0.26 and 0.66. Trace metal levels in toenails did not correlate well with those in the blood and urine and showed low-moderate correlation with those in the hair and fingernails.This work was supported by FIS grants PI12/00150, PI17CIII/00034 & PI18/00287 (Instituto de Salud Carlos III, State Secretary of R + D + I and European Union (ERDF/ESF, "Investing in your future"))

Specific fatty acid intake and the risk of pancreatic cancer in Canada

The possible association of specific fatty acid (FA) intake and pancreatic cancer risk was investigated in a population-based case–control study of 462 histologically confirmed cases and 4721 frequency-matched controls in eight Canadian provinces between 1994 and 1997. Dietary intake was assessed by means of a self-administered food frequency questionnaire. Unconditional logistic regression was used to assess associations between dietary FAs and pancreatic cancer risk. After adjustment for age, province, body mass index, smoking, educational attainment, fat and total energy intake, statistically significant inverse associations were observed between pancreatic cancer risk and palmitate (odds ratios (ORs)=0.73; 95% confidence intervals (CIs) 0.56–0.96; P-trend=0.02), stearate (OR=0.70; 95% CI 0.51–0.94; P-trend=0.04), oleate (OR=0.75; 95% CI 0.55–1.02; P-trend=0.04), saturated FAs (OR=0.67; 95% CI 0.50–0.91; P-trend=0.01), and monounsaturated FAs (OR=0.72; 95% CI 0.53–0.98; P-trend=0.02), when comparing the highest quartile of intake to the lowest. Significant interactions were detected between body mass index and both saturated and monounsaturated FAs, with a markedly reduced risk associated with intake of stearate (OR=0.36; 95% CI 0.18–0.70; P-trend=0.001), oleate (OR=0.36; 95% CI 0.19–0.72; P-trend=0.002), saturated FAs (OR=0.35; 95% CI 0.18–0.67; P-trend=0.002), and monounsaturated FAs (OR=0.32; 95% CI 0.16–0.63; P-trend<0.0001) among subjects who are obese. The results suggest that substituting polyunsaturated FAs with saturated or monounsaturated FAs may reduce pancreatic cancer risk, independently of total energy intake, particularly among obese subjects

Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast

BACKGROUND: Viruses including Epstein–Barr virus (EBV), a human equivalent of murine mammary tumour virus (MMTV) and human papillomavirus (HPV) have been implicated in the aetiology of human breast cancer. We report the presence of HPV DNA sequences in areolar tissue and tumour tissue samples from female patients with breast carcinoma. The presence of virus in the areolar–nipple complex suggests to us a potential pathogenic mechanism. METHODS: Polymerase chain reaction (PCR) was undertaken to amplify HPV types in areolar and tumour tissue from breast cancer cases. In situ hybridisation supported the PCR findings and localised the virus in nipple, areolar and tumour tissue. RESULTS: Papillomavirus DNA was present in 25 of 29 samples of breast carcinoma and in 20 of 29 samples from the corresponding mamilla. The most prevalent type in both carcinomas and nipples was HPV 11, followed by HPV 6. Other types detected were HPV 16, 23, 27 and 57 (nipples and carcinomas), HPV 20, 21, 32, 37, 38, 66 and GA3-1 (nipples only) and HPV 3, 15, 24, 87 and DL473 (carcinomas only). Multiple types were demonstrated in seven carcinomas and ten nipple samples. CONCLUSIONS: The data demonstrate the occurrence of HPV in nipple and areolar tissues in patients with breast carcinoma. The authors postulate a retrograde ductular pattern of viral spread that may have pathogenic significance

A cohort study of in utero polychlorinated biphenyl (PCB) exposures in relation to secondary sex ratio

Abstract: Background: Polychlorinated biphenyls (PCBs) are ubiquitous industrial chemicals that persist in the environment and in human fatty tissue. PCBs are related to a class of compounds known as dioxins, specifically 2,3,7,8-TCDD (tetrachloro-dibenzodioxin), which has been implicated as a cause of altered sex ratio, especially in relation to paternal exposures. Methods: In the 1960's, serum specimens were collected from pregnant women participating in the Child Health and Development Study in the San Francisco Bay Area. The women were interviewed and their serum samples stored at -20°C. For this study, samples were thawed and a total of eleven PCBs were determined in 399 specimens. Secondary sex ratio, or sex ratio at birth, was evaluated as a function of maternal serum concentrations using log-binomial and logistic regression, controlling for hormonally active medications taken during pregnancy. Results: The relative risk of a male birth decreased by 33% comparing women at the 90th percentile of total PCBs with women at the 10th percentile (RR = 0.67; 95% CI, 0.48–0.94; p = 0.02), or by approximately 7% for each 1 μg/L increase in total PCB concentration. Although some congener-specific associations with sex ratio were only marginally statistically significant, all nine PCB congeners with < 30% of samples below the LOQ showed the same direction of association, an improbable finding under the null hypothesis. Conclusion: Maternal exposure to PCBs may be detrimental to the success of male sperm or to the survival of male embryos. Findings could be due to contaminants, metabolites or PCBs themselves

Pharmacokinetics and tissue distribution of PGG–paclitaxel, a novel macromolecular formulation of paclitaxel, in nu/nu mice bearing NCI-460 lung cancer xenografts

PGG–PTX is a water-soluble formulation of paclitaxel (PTX), made by conjugating PTX to poly(l-γ-glutamylglutamine) acid (PGG) via ester bonds, that spontaneously forms a nanoparticle in aqueous environments. The purpose of this study was to compare the pharmacokinetics and tissue distribution of PTX following injection of either free PTX or PGG–PTX in mice. Both [3H]PTX and PGG–[3H]PTX were administered as an IV bolus injection to mice bearing SC NCI-H460 lung cancer xenografts at a dose of 40-mg PTX equivalents/kg. Plasma, tumor, major organs, urine, and feces were collected at intervals out to 340 h. Total taxanes, taxane extractable into ethyl acetate, and native PTX were quantified by liquid scintillation counting and HPLC. Conjugation of PTX to the PGG polymer increased plasma and tumor C max, prolonged plasma half-life and the period of accumulation in tumor, and reduced washout from tumor. In plasma injection of PGG–PTX increased total taxane AUC0–340 by 23-fold above that attained with PTX. In tumors, it increased the total taxane by a factor of 7.7, extractable taxane by 5.7, and native PTX by a factor of 3.5-fold. Conjugation delayed and reduced total urinary and fecal excretion of total taxanes. Incorporation of PTX into the PGG–PTX polymer significantly prolonged the half-life of total taxanes, extractable taxane, and native PTX in both the plasma and tumor compartments. This resulted in a large increase in the amount of active PTX delivered to the tumor. PGG–PTX is an attractive candidate for further development

Sentinel node detection in N0 cancer of the pharynx and larynx

Neck lymph node status is the most important factor for prognosis in head and neck squamous cell carcinoma. Sentinel node detection reliably predicts the lymph node status in melanoma and breast cancer patients. This study evaluates the predictive value of sentinel node detection in 50 patients suffering from pharyngeal and laryngeal carcinomas with a N0 neck as assessed by ultrasound imaging. Following 99m-Technetium nanocolloid injection in the perimeter of the tumour intraoperative sentinel node detection was performed during lymph node dissection. Postoperatively the histological results of the sentinel nodes were compared with the excised neck dissection specimen. Identification of sentinel nodes was successful in all 50 patients with a sensitivity of 89%. In eight cases the sentinel node showed nodal disease (pN1). In 41 patients the sentinel node was tumour negative reflecting the correct neck lymph node status (pN0). We observed one false-negative result. In this case the sentinel node was free of tumour, whereas a neighbouring lymph node contained a lymph node metastasis (pN1). Although we have shown, that skipping of nodal basins can occur, this technique still reliably identifies the sentinel nodes of patients with squamous cell carcinoma of the pharynx and larynx. Future studies must show, if sentinel node detection is suitable to limit the extent of lymph node dissection in clinically N0 necks of patients suffering from pharyngeal and laryngeal squamous cell carcinoma