Ractopamine and Other Growth-Promoting Compounds in Beef Cattle Operations: Fate and Transport in Feedlot Pens and Adjacent Environments.

The current study represents a comprehensive investigation of the occurrence and fates of trenbolone acetate (TBA) and metabolites 17α-trenbolone (17α-TBOH), 17ß-TBOH, and trendione (TBO); melengesterol acetate (MGA); and the less commonly studied ß-andrenergic agonist ractopamine (RAC) in two 8 month cattle feeding trials and simulated rainfall runoff experiments. Cattle were administered TBA, MGA, or RAC, and their residues were measured in fresh feces, pen floor material, and simulated rainfall runoff from pen floor surfaces and manure-amended pasture. Concentrations of RAC ranged from 3600 ng g-1, dry weight (dw), in pen floor to 58 000 ng g-1 in fresh feces and were, on average, observed at 3-4 orders of magnitude greater than those of TBA and MGA. RAC persisted in pen floors (manure t1/2 = 18-49 days), and contamination of adjacent sites was observed, likely via transport of windblown particulates. Concentrations in runoff water from pen floors extrapolated to larger-scale commercial feedlots revealed that a single rainfall event could result in mobilization of gram quantities of RAC. This is the first report of RAC occurrence and fate in cattle feedlot environments, and will help understand the risks posed by this chemical and inform appropriate manure-management practices.

Occupational silica exposure as a risk factor for scleroderma: a meta-analysis.

OBJECTIVES: Among potential environmental risk factors for systemic sclerosis (SSc), occupational exposures have received some attention. In this meta-analysis, we examined the association between SSc and occupational exposure to silica. METHODS: We searched Medline, Toxline, BIOSIS, and Embase (1949 and November 2009) for original articles published in any language. Sixteen studies are included in the analysis, of which, 3 are cohort studies, 9 case-control and 4 are of other designs. The combined estimator of relative risk (CERR) and 95% confidence interval (CI) were calculated using fixed or random effect models. RESULTS: Significant heterogeneity was detected (I (2) = 97.2%; P < 0.01), and the CERR was 3.20 (95% CI, 1.89-5.43). The CERR for studies in females was 1.03 (95% CI, 0.74-1.44) and was 3.02 (95% CI, 1.24-7.35) for males. The CERR for case-control studies was 2.24 (95% CI, 1.65-3.31) and was 15.49 (95% CI, 4.54-52.87) for cohort studies. CONCLUSIONS: The findings suggest that silica exposure may be a significant risk factor for developing SSc and specifically in males. Further observational studies examining the role of occupational silica exposure in the context of other risk factors are needed.

Effects of anti-transforming growth factor-beta antibody and interleukin-2 in tumor-bearing mice.

In previous studies we found that the immunosuppression seen in mice bearing Herpes virus type 2-transformed (H238) fibrosarcoma was likely to be due to tumor-derived transforming growth factor-beta (TGF-beta). In vitro experiments showed that interleukin-2 (IL-2) and antibodies against TGF-beta could significantly counteract TGF-beta-induced depression in lymphocytes. The present study was performed to determine if the administration of polyclonal anti-TGF-beta antibody and recombinant IL-2, alone or in combination, could inhibit H238 tumor progression in vivo and to investigate possible mechanisms of action. The tumor cells were injected s.c. at 1 x 10(6) cells/mouse and treatments were given 1-10 days post-injection. In phase I, a total of 25,000 units of IL-2 (5,000 units/injection) and/or 900 ng of anti-TGF-beta (100 ng/injection) were administered i.p. per animal. Phase II was conducted similarly, except that each mouse received a total of 127,500 units of IL-2, either with or without the same amount of antibody. No treatment-related toxicity was noted. Tumor volumes were monitored for 16-18 days after tumor implantation. The H238 tumors in treated mice from both both phases grew as rapidly as, or significantly faster than, in untreated controls. Significant enhancement of tumor growth was found in the groups given IL-2 as a single agent, regardless of total dose. The combination of the higher IL-2 dose with anti-TGF-beta resulted in more rapid tumor progression than in animals given the antibody alone. Relative spleen weights, peripheral blood leukocyte counts, and the chemiluminescent oxidative burst of phagocytes were significantly elevated in all tumor-bearing mice, whereas T cell response to mitogenic stimulation was depressed. However, the oxidative burst capacity of spleen (but not blood) cells and natural killer cell cytotoxicity were markedly lower in the treated groups compared to nontreated tumor-bearing controls. In contrast, plasma levels of tumor necrosis factor-alpha and IL-2 were substantially higher in the group given both modalities (phase II) compared to the other treated groups. These findings show that anti-TGF-beta antibody, both with and without low-dose IL-2 regimens, can be safely administered in vivo. However, tumor growth was not delayed by the treatment protocols used. The induction of hyporesponsiveness in certain cell types may account, at least partly, for the enhancement seen in tumor progression.