Major environmental characteristics of swine husbandry that affect exposure to dust and airborne endotoxins.

Inhalation of organic dust or endotoxin in the dust is considered a major risk factor for occupational respiratory illnesses. Eighteen environmental characteristics associated with animal husbandry were surveyed at 36 swine farms in seven provinces throughout South Korea. Association of these factors with levels of indoor inhalable or respirable dust or endotoxin in each type of dust was analyzed using backward stepwise multiple linear regression models. Mean levels of inhalable and respirable dust were 0.5 ± 0.35 and 0.13 ± 0.12 mg/m3 air, respectively, and mean endotoxin levels were 676 ± 463 and 48.4 ± 68.2 EU/m3, respectively, in each dust. Factors negatively associated with inhalable dust levels included pig age, indoor farm temperature, number of pigs in the building, hr/week of indoor farm work, and partly slatted floor. Factors positively associated with inhalable dust levels included floor cleaning by manual scraping and slurry deposit duration. Factors negatively associated with the level of endotoxin in inhalable dust included pig age, temperature, number of pigs, hr/week of indoor farm work, and partly slatted floor. Factors negatively associated with respirable dust level included area of the confinement building, whereas factors positively associated with respirable dust level included the number of pigs and stocking density. Endotoxin levels in respirable dust were negatively associated with h/week of indoor farm work and partly slatted floor. Overall, data suggest that husbandry variables may be adjusted to control dust and airborne endotoxin levels in swine farms.

Recombinant erythroid differentiation regulator 1 inhibits both inflammation and angiogenesis in a mouse model of rosacea.

The erythroid differentiation regulator 1 (Erdr1), which is a novel and highly conserved factor, was recently reported to be negatively regulated by IL-18 and to play a crucial role as an antimetastatic factor. IL-18 is a proinflammatory cytokine that functions as an angiogenic mediator in inflammation. Rosacea is a chronic inflammatory skin disorder that is characterized by abnormal inflammation and vascular hyperactivity of the facial skin. To determine whether Erdr1 contributes to the regulation of the chronic inflammatory process in the development of rosacea, an immunohistochemical analysis was performed in healthy donors and patients with rosacea. In this study, we showed that Erdr1 was downregulated, whereas IL-18 was upregulated, in patients with rosacea, which led us to question the role of Erdr1 in this disorder. Moreover, a rosacea-like BALB/c mouse model was used to determine the role of Erdr1 in rosacea in vivo. LL-37 injection induced typical rosacea features, including erythema, telangiectasia and inflammation. Treatment with recombinant Erdr1 (rErdr1) resulted in a significant reduction of erythema, inflammatory cell infiltration (including CD4(+) and CD8(+) T cells), and microvessel density with vascular endothelial growth factor (VEGF). Taken together, our findings suggest that rErdr1 may be involved in attenuating the inflammation and angiogenesis associated with the pathogenesis of rosacea. Thus, these results provide new insight into the mechanism involved in this condition and indicate that rErdr1 could be a potential target for therapeutic intervention of rosacea.

Anti-angiogenic effect of the seed extract of Benincasa hispida Cogniaux.

Benincasa hispida in Korea was used mainly diabetes and diuresis diseases. This study was carried out to evaluate anti-angiogenic effect of the seed extract of Benincasa hispida Cogniaux. Basic fibroblast growth factor (bFGF) is a potent angiogenic factor found in various tumors. In this study, we found that the seed extract of Benincasa hispida Cogniaux decreased bFGF-induced endothelial cell proliferation and tube formation in a dose-dependent manner. Besides, Benincasa hispida seed extract showed no cytotoxicity on HUVECs and normal fibroblast cells. Furthermore, the seed extract of Benincasa hispida showed a potent inhibitory effect on bFGF-induced angiogenesis in vivo. These results suggest that the seed extract of Benincasa hispida inhibits the proliferation of endothelial cells induced by bFGF, which may explain its anti-angiogenic properties.

Topoisomerase I inactivation by reticulol and its in vivo cytotoxicity against B16F10 melanoma.

To investigate the enzyme-inhibitory efficacy and the cytotoxicity of reticulol produced from a strain of Streptoverticillium, we conducted a DNA topoisomerase (Topo) cleavage assay and an in vivo assay using B16F10 melanoma. From the inhibition assay of reticulol for Topo I, which is involved in melanoma metastasis, it was seen that Topo I treated with 45 microM reticulol did not replicate or transcribe DNA by forming supercoiled DNA. In the annexin V/propidium iodide staining assay to investigate the death pattern of B16F10 cells treated with 200 microM reticulol, proliferation of B16F10 cells was inhibited due to necrosis. Furthermore, from the in vivo assay, reticulol combined with Adriamycin (a mixture with retinolol 5 mg/kg and Adriamycin 1 mg/kg) further retarded the tumor growth compared to that in mice treated with Adriamycin alone (1 mg/kg). The survival rate of tumor-bearing mice treated with the mixture was closely associated with its cytotoxicity. Taken together, these results suggested that reticulol inactivates Topo I, which is involved in tumor metastasis, and exhibits excellent cytotoxic efficacy against B16F10 melanoma, when combined with Adriamycin, in a mouse model.

Antitumor efficacy of reticulol from Streptoverticillium against the lung metastasis model B16F10 melanoma. Lung metastasis inhibition by growth inhibition of melanoma.

Reticulol was isolated from the culture broth of the strain Streptoverticillium sp. NA-4803. Recticulol (M.W. 222.2) exhibited a potent in vitro cytotoxicity against A427, a human lung tumor cell line, and B16F10, a mouse melanoma cell line. In the trypan blue staining assay for B16F10 cells, the cell viability by reticulol treatment was significantly decreased in a dose-dependent manner. The in vivo assay for the lung metastasis-blocking effect showed that reticulol injected intravenously suppressed the increase in colonies on the lung in a dose-dependent manner. In addition, the survival rate of tumor-implanted mice treated with reticulol was closely associated with its antitumoral efficacy. Reticulol administered via the peritoneum of mice showed less metastasis inhibition than that injected intravenously. To demonstrate the mechanism for inhibition of metastasis, the inhibitory effect of reticulol for matrix metalloproteinase-2 or -9 involved in melanoma metastasis was investigated; however, they were not observed on zymogram gel. In addition, the antitumor efficacy of reticulol was not associated with cell cycle arrest or apoptosis. Therefore, it was inferred that reticulol known as a phosphodiesterase inhibitor directly inhibited the growth of B16F10 melanoma, showing necrotic response. These results suggest that reticulol protects its lung metastasis via the bloodstream by inhibiting the growth of B16F10 melanoma at the cellular level.