1,3-Butadiene has been assessed as a Priority Substance under the Canadian Environmental Protection Act. The general population in Canada is exposed to 1,3-butadiene primarily through ambient air. Inhaled 1,3-butadiene is carcinogenic in both mice and rats, inducing tumors at multiple sites at all concentrations tested in all identified studies. In addition, 1,3-butadiene is genotoxic in both somatic and germ cells of rodents. It also induces adverse effects in the reproductive organs of female mice at relatively low concentrations. The greater sensitivity in mice than in rats to induction of these effects by 1,3-butadiene is likely related to species differences in metabolism to active epoxide metabolites. Exposure to 1,3-butadiene in the occupational environment has been associated with the induction of leukemia; there is also some limited evidence that 1,3-butadiene is genotoxic in exposed workers. Therefore, in view of the weight of evidence of available epidemiological and toxicological data, 1,3-butadiene is considered highly likely to be carcinogenic, and likely to be genotoxic, in humans. Estimates of the potency of butadiene to induce cancer have been derived on the basis of both epidemiological investigation and bioassays in mice and rats. Potencies to induce ovarian effects have been estimated on the basis of studies in mice. Uncertainties have been delineated, and, while there are clear species differences in metabolism, estimates of potency to induce effects are considered justifiably conservative in view of the likely variability in metabolism across the population related to genetic polymorphism for enzymes for the critical metabolic pathway.
Insulin-dependent (type 1) diabetes is a prototypic organ-specific autoimmune disease resulting from the selective destruction of insulin-secreting beta cells within pancreatic islets of Langerhans by an immune-mediated inflammation involving autoreactive CD4(+) and CD8(+) T lymphocytes which infiltrate pancreatic islets. Current treatment is substitutive, i.e. chronic use of exogenous insulin which, in spite of significant advances, is still associated with major constraints (multiple daily injections, risks of hypoglycaemia) and lack of effectiveness over the long term in preventing severe degenerative complications. Finding a cure for autoimmune diabetes by establishing effective immune-based therapies is a real medical health challenge, as the disease incidence increases steadily in industrialized countries. As the disease affects mainly children and young adults, any candidate immune therapy must therefore be safe and avoid a sustained depression of immune responses with the attendant problems of recurrent infection and drug toxicity. Thus, inducing or restoring immune tolerance to target autoantigens, controlling the pathogenic response while preserving the host reactivity to exogenous/unrelated antigens, appears to be the ideal approach. Our objective is to review the major progress accomplished over the last 20 years towards that aim. In addition, we would like to present another interesting possibility to access new preventive strategies based on the 'hygiene hypothesis', which proposes a causal link between the increasing incidence of autoimmune diseases, including diabetes, and the decrease of the infectious burden. The underlying rationale is to identify microbial-derived compounds mediating the protective activity of infections which could be developed therapeutically.
Cites: J Immunol. 2000 Jun 1;164(11):5683-810820244
There is some evidence to suggest that workers in animal-related occupations are at increased risk of developing lymphohematopoietic cancers. This study aimed to examine the risk of leukemia, non-Hodgkin's lymphoma (NHL), and multiple myeloma associated with occupational exposure to animals.
We used data from a multi-site, population-based case-control study using mailed questionnaires which had taken place in eight of ten Canadian provinces, during 1994-1998. There were 1023 leukemia cases, 1577 NHL cases, and 324 multiple myeloma cases (all histologically confirmed) and 4688 population-based controls. Animal-related occupations were identified from a lifetime occupational history. Subjects in animal-related jobs were compared with others using logistic regression for the risk of leukemia, NHL, and multiple myeloma.
Compared to subjects without occupational exposure to animals, occupational exposure to beef cattle increased the risks of leukemia (odds ratio (OR) 2.0, 95% confidence interval (CI) 1.2-3.3) and NHL (OR 1.8, 95% CI 1.1-2.9). No other animal exposure was consistently associated with risk of lymphohematopoietic cancer. An unexpected protective association was observed between work as a fisherman and leukemia (OR 0.4, 95% CI 0.2-0.8) and NHL (OR 0.6, 95% CI 0.4-0.9).
This population-based case-control study found that those individuals working in occupations associated with beef cattle are at increased risk for developing leukemia and lymphoma while those working in occupations requiring the handling of fish are at decreased risk of leukemia and lymphoma.
To investigate the prevalence of concurrent methicillin-resistant Staphylococcus aureus (MRSA) colonization in people and pets in the same household with a person or pet with an MRSA infection and to compare MRSA isolates by use of molecular techniques.
24 dogs, 10 cats, and 56 humans in part 1 and 21 dogs, 4 cats, and 16 humans in part 2 of the study.
In both parts of the study, nasal swab specimens were collected from humans and nasal and rectal swab specimens were collected from household pets. Selective culture for MRSA was performed, and isolates were typed via pulsed-field gel electrophoresis (PFGE) and spa typing. Households were defined as positive when MRSA was isolated from at least 1 person (part 1) or 1 pet (part 2).
In part 1, 6 of 22 (27.3%) households were identified with MRSA colonization in a person. In these households, 10 of 56 (17.9%) humans, 2 of 24 (8.3%) dogs, and 1 of 10 (10%) cats were colonized with MRSA. In part 2, only 1 of 8 households was identified with MRSA colonization in a pet. Most MRSA isolates obtained from humans and pets in the same household were indistinguishable by use of PFGE.
The high prevalence of concurrent MRSA colonization as well as identification of indistinguishable strains in humans and pet dogs and cats in the same household suggested that interspecies transmission of MRSA is possible. Longitudinal studies are required to identify factors associated with interspecies transmission.