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Structure-based grouping of chemicals for targeted testing and read-across is an efficient way to reduce resources and animal usage. For substances of unknown or variable composition, complex reaction products, or biological materials (UVCBs), structure-based grouping is virtually impossible. Biology-based approaches such as metabolomics could provide a solution. Here, 15 steam-cracked distillates, registered in the EU through the Lower Olefins Aromatics Reach Consortium (LOA), as well as six of the major substance constituents, were tested in a 14-day rat oral gavage study, in line with the fundamental elements of the OECD 407 guideline, in combination with plasma metabolomics. Beyond signs of clinical toxicity, reduced body weight (gain), and food consumption, pathological investigations demonstrated the liver, thyroid, kidneys (males only), and hematological system to be the target organs. These targets were confirmed by metabolome pattern recognition, with no additional targets being identified. While classical toxicological parameters did not allow for a clear distinction between the substances, univariate and multivariate statistical analysis of the respective metabolomes allowed for the identification of several subclusters of biologically most similar substances. These groups were partly associated with the dominant (> 50%) constituents of these UVCBs, i.e., indene and dicyclopentadiene. Despite minor differences in clustering results based on the two statistical analyses, a proposal can be made for the grouping of these UVCBs. Both analyses correctly clustered the chemically most similar compounds, increasing the confidence that this biological approach may provide a solution for the grouping of UVCBs. [ABSTRACT FROM AUTHOR]

Accurate determination of cell number is essential for the quantitative description of biological processes. The changes should be related to a measurable reference e.g. in the case of cell culture, the viable cell number is a very valuable reference parameter. Indirect methods of cell number/viability measurements may have up to 10 % standard deviation. This can lead to undesirable large deviations in the analysis of '- omics' data as well as time course studies. Such data should be preferably normalized to the exact viable cell number at a given time to allow meaningful interpretation and understanding of the biological processes. Manual counting of cell number is very laborious and not possible in certain experimental setups. We therefore, developed a simple and reliable fluorescence based method with an accuracy of 95-98 % for the determination of the viable cell number in situ. We optimized the seeding cell densities for primary rat hepatocytes for optimal cell adhesion. This will help in efficient use of primary cells which are usually limited in availability. The method will be very useful in the application of '- omics' techniques, especially metabolome analysis where the specific rates of uptake/production of metabolites can be reliably calculated. [ABSTRACT FROM AUTHOR]

Dehydroepiandrostreone (DHEA) is a neuroactive steroid produced by the inner layer of the adrenal cortex close to the adrenomedullary cells. Chromaffin cell growth and proliferation are under the control of insulin-like growth factor II (IGF-II) and basic fibroblast growth factor (bFGF). The aim of the present study was to examine the role of DHEA on chromaffin cell proliferation induced by IGF-II and bFGF. In our model, DHEA significantly decreased IGF-II-induced proliferation by 48.7%, whereas it did not affect the proliferation induced by bFGF. These data suggest that DHEA exerts a paracrine function in the control of chromaffin cell growth. [ABSTRACT FROM AUTHOR]

Objective: To determine whether naproxen, a propionic acid inhibitor of cyclooxygenase, alters the course of experimental rhinovirus colds.Design: A randomized, double-blind, controlled trial.Setting: Rhinovirus challenge model in volunteers cloistered in individual hotel rooms.Volunteers: Eighty-seven healthy young adults with serum neutralizing antibody titers of less than or equal to 1:2 to the challenge virus; 79 were evaluable.Intervention: Thirty-nine participants received naproxen (loading dose, 400 mg or 500 mg followed by 200 mg or 500 mg three times daily for 5 days). Forty participants received placebo. Treatment was started 6 hours after viral challenge.Measurements: Daily measurement of viral titers, symptoms, nasal mucus production, and nasal tissue use; incidence of infection and illness; and measurement of homotypic serum neutralizing antibody responses.Results: Viral titers and serum homotypic antibody responses were similar in the naproxen and placebo groups. Significant reductions in headache, malaise, myalgia, and cough occurred in the naproxen group. A 29% reduction was noted in the total (5-day) symptom score in the naproxen group (95% CI, 16% to 42%).Conclusion: Naproxen treatment did not alter virus shedding or serum neutralizing antibody responses in participants with experimental rhinovirus colds, but it had a beneficial effect on the symptoms of headache, malaise, myalgia, and cough. Prostaglandins may be among the inflammatory mediators that play a role in the pathogenesis of rhinovirus colds. [ABSTRACT FROM AUTHOR]

Background In 2009, the General Medical Council (GMC) updated its guidance on consent, introducing a new statement that employees should be offered the opportunity to view reports, before the reports are sent to the employer. Aims To investigate the effects of this change on the perceptions and practice of occupational physicians. Methods A cross-sectional survey of UK occupational physicians via the Society of Occupational Medicine e-newsletter, seeking their opinions of the anticipated and actual effects of the guidance on employers, employees, occupational physicians and occupational health services. Results Two hundred and ninety-five completed questionnaires were returned (estimated response rate 30%). Respondents included 25% of accredited UK specialists. Some reported improved standards and greater transparency, however the change was generally perceived as unfavourable, with employee and employer losses: 50% reported delay providing timely advice to employers and 35% reported delays in employees returning to work. Significant variation in practice and increased costs were reported, with variable effects on different services. Difficulties in areas such as pensions and health surveillance were reported. Some occupational physicians had moved to instant reporting; others had moved away from this to allow more care with wording of reports. Conclusions We found significant variations in practice between occupational physicians and concerns of employee and employer losses as a result of changes to the GMC consent guidance. Clearer guidance on practical implementation was desired. The background ethical reasoning should be stated so that the parameters of the guidance are delineated and its reach should be clarified. [ABSTRACT FROM PUBLISHER]