Mortality risk among workers with exposure to dioxins.

BACKGROUND: In several studies, dioxin exposure has been associated with increased risk from several causes of death. AIMS: To compare the mortality experience of workers exposed to dioxins during trichlorophenol (TCP) and pentachlorophenol (PCP) production to that of the general population and to examine mortality risk by estimated exposure levels. METHODS: A retrospective cohort study which followed up workers' vital status from 1940 to 2011, with serum surveys to support estimation of historical dioxin exposure levels. RESULTS: Among the 2192 study subjects, there were nine deaths in TCP workers from acute non-lymphatic leukaemia [standardized mortality ratio (SMR) = 2.88, 95% confidence interval (CI) 1.32-5.47], four mesothelioma deaths (SMR = 5.12, 95% CI 1.39-13.10) and four soft tissue sarcoma (STS) deaths (SMR = 3.08, 95% CI 0.84-7.87). In PCP workers, there were eight deaths from non-Hodgkin's lymphoma (SMR = 1.92, 95% CI 0.83-3.79), 150 from ischaemic heart disease (SMR = 1.20, 95% CI 1.01-7.89) and five from stomach ulcers (SMR = 3.38, 95% CI 1.10-7.89). There were no trends of increased mortality with increased dioxin exposure except for STS and 2,3,7,8-tetrachlorodibenzo-p-dioxin levels. This finding for STS should be interpreted with caution due to the small number of deaths and the uncertainty in diagnosis and nosology. CONCLUSIONS: While some causes of death were greater than expected, this study provides little evidence of increased risk when dioxin exposures are considered.

"Intrinsic" elimination rate and dietary intake estimates for selected indicator PCBs: toxicokinetic modeling using serial sampling data in US subjects, 2005-2010.

Changes in measured concentrations of persistent compounds such as polychlorinated biphenyls (PCBs) in an individual over time reflect not only intrinsic elimination rates but also any ongoing intake of the compounds and changes in the volume of distribution. Thus, "apparent" elimination rates calculated from data on changes in serum lipid-adjusted concentration may over- or under-estimate the "intrinsic" elimination rates for such compounds. Serum PCB concentrations were measured in 43 individuals approximately 5years apart. Changes in measured concentrations and body weights were used to estimate mass-based apparent elimination rates. The changes in estimated body mass of PCBs 105, 118, 138, 153, and 180 were input into a simple first-order model employing previously estimated intrinsic elimination rates to estimate congener-specific average dietary intake rates over the period between samples. Calculated median dietary intakes were compared to previous estimates. Intrinsic elimination rates were adjusted for two congeners. The analyses support central tendencies of intrinsic elimination rates of approximately 5years for PCBs 105 and 118, 11years for PCB 138, 14.4years for PCB 153, and 20years or more for PCB 180. Estimated dietary intakes for this population and time period depend on the assumed intrinsic elimination rates and range from 0.1ngkg(-1)d(-1) for PCB 105 to approximately 1-2ngkg(-1)d(-1) for PCB 180. Estimated body burdens of PCB 180 changed very little over the five-year period, suggesting near steady-state exposure levels. As a result, estimates for both elimination half-life and ongoing intake rates for this congener are highly uncertain.

Pancreatic small cells: analysis of quiescence, long-term maintenance and insulin expression in vitro.

We have previously identified a novel population of small cells in human and canine pancreas characterized by immature morphology, quiescence, and a glucose-responsive insulin secretion. Based on their immature phenotype and predominant presence in small islets, we have hypothesized that small cells serve as islet progenitors. This hypothesis remains untested, however, due to persistent quiescence and scarcity of small cells in vitro. We have recently developed a culture medium that allowed for modest small cell proliferation. In this study we characterized the expression of genes potentially involved in small cell growth regulation by Q-RT-PCR. Our results suggest that quiescence of small cells correlates with up-regulation of Cdk inhibitors p27(Kip1), p16(INK4a) and p21(CIP1), PTEN, Hep27 and Foxo1a and with down-regulation of c-Myc and the receptors for EGF, FGF2 and HGF. The exit from quiescence correlates with activation of EGFR expression and down-regulation of p27(Kip1) and p16(INK4a). We also report here that small cells can be maintained in long-term non-adherent cultures preserving insulin and glucagon production for up to 208 days. Therefore, expansion of small cells in vitro may have a significant potential for the treatment of diabetes. This study is an important step in understanding the mechanisms involved in small cell growth regulation, which is required to fully evaluate their functional potential.

Mortality rates among chemical workers in the Kanawha Valley of West Virginia: 1940-1999.

To expand a cohort of chemical workers in the Kanawha Valley, we conducted a study of 33,225 workers who were employed at three locations between 1940 and 1999. We observed no increase in overall cancer mortality. Higher risk estimates were observed for lymphosarcoma and reticulosarcoma among hourly employees who worked at the Institute or South Charleston locations. This finding was limited to men hired before 1960. We observed no new cases of angiosarcoma of the liver, a cause of death previously reported in association with vinyl chloride production at the South Charleston location. Specific risk factors for lymphosarcoma and reticulosarcoma have not been identified in previous targeted studies of this population and it is unlikely that additional cause-specific research will elucidate the etiology. Updates of the entire cohort will continue and can be used as a comparison population for chemical specific studies within these three plants.

[Experimentation of apiarian preparations for the direct and the indirect capping of the dental pulp]. / Experimentarea unor preparate apicole în coafajul indirect si direct al pulpei dentare.

With a view to extend the range of biologically active preparations for the direct and the indirect capping of the dental pulp the authors have used a paste made from an alcoholic solution of propolis and zincoxyde. The study was carried on in 150 teeth with indirect capping of deep cavities, and 50 teeth with direct capping. The evolution of the cappings was followed clinically, radiologically and morphologically. The results obtained showed that the paste with propolis exerts effects similar to those of zinc eugenate. The morphologic study of the indirect capping showed that secondary dentin developed shortly after the application of the paste, and that it was followed by the development of pulpolites and the sclerous transformation of the pulp. In teeth with direct capping a protective film developed at the opening of the dental chamber. With time the pulpal wound undergoes cicatrization by a process of fibrosis and there is a trend to remineralization. No areas of pulpal degenerescence were found the rest of the pulpal tissue, and this suggests that the paste is more histophilic than the pastes based on calcium hydroxide, with which an area of necrosis occurred at the opening of the chamber, and calcium and fibrous degenerescence occurred in the coronal pulp.

The role of solvents in the stabilization of helical structure: the low pH ribo A8 and A10 double helices in mixed solvents.

The order-disorder transitions of the double helices formed by the ribo-oligoadenylic acids rA8 and rA10 at pH 4.2 have been investigated in a series of organic/aqueous mixed solvents. Melting temperature data, Tm, derived from the uv melting curves were used to define the stability of the double helices in the different mixed solvent systems. It was found that the extent of helix destabilization depended in a predictable fashion on both the quantity and the nature of the added organic solvents. For the C1 through C4 aliphatic alcohols, the longer, less branched alcohols proved to be more effective destabilizers of the helical structure. Significantly, the amides proved to be more powerful destabilizers than the alcohols. Analysis of the melting curves provided the Van't Hoff enthalpy change for each transition. The data are interpreted in terms of the role of solvent in the stabilization of ribonucleic acid structure.