Wijnhoven, Susan W P; Hoogervorst, Esther M; Waard, Harm de; Horst, Gijsbertus T J van der; Steeg, Harry van (2007-01-03)
Several mouse models with defects in genes encoding components of the nucleotide excision repair (NER) pathway have been developed. In NER two different sub-pathways are known, i.e. transcription-coupled repair (TC-NER) and global-genome repair (GG-NER). A defect in one particular NER protein can lead to a (partial) defect in GG-NER, TC-NER or both. GG-NER defects in mice predispose to cancer, both spontaneous as well as UV-induced. As such these models (Xpa, Xpc and Xpe) recapitulate the human xeroderma pigmentosum (XP) syndrome. Defects in TC-NER in humans are associated with Cockayne syndrome (CS), a disease not linked to tumor development. Mice with TC-NER defects (Csa and Csb) are - except for the skin - not susceptible to develop (carcinogen-induced) tumors. Some NER factors, i.e. XPB, XPD, XPF, XPG and ERCC1 have functions outside NER, like transcription initiation and inter-strand crosslink repair. Deficiencies in these processes in mice lead to very severe phenotypes, like trichothiodystrophy (TTD) or a combination of XP and CS. In most cases these animals have a (very) short life span, display segmental progeria, but do not develop tumors. Here we will overview the available NER-related mouse models and will discuss their phenotypes in terms of (chemical-induced) tissue-specific tumor development, mutagenesis and premature aging features.
Jong, Nynke de; Klungel, Olaf H; Verhagen, Hans; Wolfs, Marion C J; Ocké, Marga C; Leufkens, Hubert G M (2007-05-19)
Current regulations focus on the mandatory safety evaluation of functional foods before they come to market, but Nynke de Jong and colleagues argue that the effects of such foods should also be evaluated after they have been launched
Carfi', M; Gennari, A; Malerba, I; Corsini, E; Pallardy, M; Pieters, R; Loveren, Henk van; Vohr, H W; Hartung, T; Gribaldo, L (2007-01-05)
The implementation of Registration, Evaluation and Authorisation of new and existing Chemicals (REACH) will increase the number of laboratory animals used, if alternative methods will not be available. In the meantime, REACH promotes the use of in vitro tests and, therefore, a set of appropriated alternative testing methods and assessment strategies are needed. The immune system can be a target for many chemicals including environmental contaminants and drugs with potential adverse effects on human health. The aim of this study was to evaluate the predictivity of a set of in vitro assays to detect immunosuppression. The tests have been performed on human, rat and murine cells. Different endpoints have been assessed: cytotoxicity, cytokine release, myelotoxicity and mitogen responsiveness. For each of these endpoints IC50s values have been calculated. Six chemical substances, representative of the full range of in vivo responses and for which good human and/or animal data are available either from databases or literature, have been selected: two chemicals classified as not immunotoxic (Urethane and Furosemide), and four (tributyltin chloride (TBTC), Verapamil, Cyclosporin A, Benzo(a)pyrene) with different effect on immune system. All the tests confirmed the strong immunotoxic effect of TBTC as well as they confirmed the negative controls. For one chemical (Verapamil) the IC50 is similar through the different tests. The IC50s obtained with the other chemicals depend on the endpoints and on the animal species. The clonogenic test (CFU-GM) and the mitogen responsiveness showed similar IC50s between human and rodent cells except for Cyclosporin A and TBTC. All different tests classified the compounds analyzed in the same way.
Vogt, M; Derendorf, H; Krämer, J; Junginger, H E; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M (2007-01-01)
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing prednisolone are reviewed. Data on its solubility, oral absorption, and permeability are not totally conclusive, but strongly suggest a BCS Class 1 classification. Prednisolone's therapeutic indications and therapeutic index, pharmacokinetics, and the possibility of excipient interactions were also taken into consideration. Available evidence indicates that a biowaiver for IR solid oral dosage forms formulated with the excipients tabulated in this article would be unlikely to expose patients to undue risks.
Jacobs-van der Bruggen, Monique A M; Bos, Griët; Bemelmans, Wanda J; Hoogenveen, Rudolf T; Vijgen, Sylvia M; Baan, Caroline A (2007-01-01)
OBJECTIVE: In the current study we explore the long-term health benefits and cost-effectiveness of both a community-based lifestyle program for the general population (community intervention) and an intensive lifestyle intervention for obese adults, implemented in a health care setting (health care intervention). RESEARCH DESIGN AND METHODS: Short-term intervention effects on BMI and physical activity were estimated from the international literature. The National Institute for Public Health and the Environment Chronic Diseases Model was used to project lifetime health effects and effects on health care costs for minimum and maximum estimates of short-term intervention effects. Cost-effectiveness was evaluated from a health care perspective and included intervention costs and related and unrelated medical costs. Effects and costs were discounted at 1.5 and 4.0% annually. RESULTS: One new case of diabetes per 20 years was prevented for every 7-30 participants in the health care intervention and for every 300-1,500 adults in the community intervention. Intervention costs needed to prevent one new case of diabetes (per 20 years) were lower for the community intervention (euro2,000-9,000) than for the health care intervention (euro5,000-21,000). The cost-effectiveness ratios were euro3,100-3,900 per quality-adjusted life-year (QALY) for the community intervention and euro3,900-5,500 per QALY for the health care intervention. CONCLUSIONS: Health care interventions for high-risk groups and community-based lifestyle interventions targeted to the general population (low risk) are both cost-effective ways of curbing the growing burden of diabetes.
Schalk, Johanna A C; Mooi, Frits R; Berbers, Guy A M; Aerts, Leon A G J M van; Ovelgönne, Hans; Kimman, Tjeerd G (2007-01-03)
DNA vaccines are based on the transfer of genetic material, encoding an antigen, to the cells of the vaccine recipient. Despite high expectations of DNA vaccines as a result of promising preclinical data their clinical utility remains unproven. However, much data is gathered in preclinical and clinical studies about the safety of DNA vaccines. Here we review current knowledge about the safety of DNA vaccines. Safety concerns of DNA vaccines relate to genetic, immunologic, toxic, and environmental effects. In this review we provide an overview of findings related to the safety of DNA vaccines, obtained so far. We conclude that the potential risks of DNA vaccines are minimal. However, their safety issues may differ case-by-case, and they should be treated accordingly.
Versteegh, A.; Brandsema, P.; Aa, M. van der; Dik, H. (Dekker en Nordemann, Rotterdam, 2007-11-01)
Ongeveer 20 procent van de zorginstellingen en zwembaden heeft in 2005 te maken gehad met een legionellabesmetting in de leidingwaterinstallatie. Dit gold ook voor 5 procent van de hotels en campings. Vooral in zorginstellingen kan Legionella in de waterleidingen gevaarlijk zijn, omdat de mensen hier vaak een zwakkere gezondheid hebben. Circa 90% van de instellingen leeft niet alle wettelijk voorgeschreven preventiemaatregelen volledig na. Bij hercontrole is echter een groot deel van de problemen opgelost. Dit toont de effectiviteit en het belang van de controles: eenmaal op de hoogte van de risico’s zijn de eigenaren meestal bereid de nodige aanpassingen te doen. Het aantal collectieve leidingwaterinstallaties met Legionella nam tussen 2000 en 2006 niet duidelijk af. Een betere naleving van de legionellapreventie regelgeving en installatievoorschriften leidt naar verwachting wél tot minder Legionella in leidingwaterinstallaties. Tussen 2000 en 2006 steeg het aantal gemelde patiënten met legionellose. Een betrouwbare schatting van het aantal patiënten dat gerelateerd is aan een collectieve leidingwaterinstallatie als besmettingsbron is echter niet mogelijk.
Kooistra, M; Franx, A; Schuitemaker, N; Wolf, H; Graafmans, W (Reed Elsevier, 2007-11)
Export search results
The export option will allow you to export the current search results of the entered query to a file. Different
formats are available for download. To export the items, click on the button corresponding with the preferred download format.
By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.
To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export.
The amount of items that can be exported at once is similarly restricted as the full export.
After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.