Objective: To determine the chemical composition of surgical smoke produced during transurethral resection of the prostate (TURP) and vaporization. Methods: A total of 12 smoke samples were collected from a continuous irrigation suction drainage system to a Tenax absorber at a 0.05 L/min flow rate during TURP and vaporization. The gases were quantitatively and qualitatively analyzed by gas chromatography-mass spectrometry (GC-MS) equipped with a purge and trap sample injector. Results:The main chemical constituents of surgical smoke produced during TURP and vaporization include propylene, allene, isobutylene, 1,3-butadiene, vinyl acetylene, mecaptomethane, ethyl acetylene, diacetylene, 1-pentene, EtOH, piperylene, propenylacetylene, 1,4-pentadiene, cyclopentadiene, acrylnitrile and butyrolactone. Three of the constituents are very toxic and carcinogenic (1,3-butadiene, vinyl acetylene and acrylonitrile). The amount (mean Ϯ standard deviation) of chemical components in the 45 L of gas and room air mixture produced during TURP and vaporization were as follows: propylene, 0.80 Ϯ 0.52 mg; isobutylene, 212.85 Ϯ 75.65 mg; 1,3-butadiene, 0.93 Ϯ 0.34 mg; ethyl acetylene, 0.09 Ϯ 0.05 mg; 1-pentene, 6.75 Ϯ 1.62 mg; 1,4-pentadiene, 0.06 Ϯ 0.02 mg; and acrylonitrile, 1.62 Ϯ 1.19 mg. Conclusions: Three of the toxic gases generated during TURP and vaporization are carcinogens (1,3-butadiene, vinyl acetylene and acrylonitrile). Therefore, higher quality filter masks, smoke evacuation devices and/or smoke filters should be developed for the safety of the operating room personnel and patients during TURP and vaporization.
Houttuynia cordata Thunb (H cordata), a medicinal plant, has anticancer activity, as it inhibits cell growth and induces cell apoptosis in cancer. However, the potential anti-cancer activity and mechanism of H cordata for human liver cancer cells is not well understood. Recently, we identified hypoxia-inducible factor (HIF)-1A, Forkhead box (FOX)O3, and MEF2A as proapoptotic factors induced by H cordata, suggesting that HIF-1A, FOXO3, and MEF2A contribute to the apoptosis of HepG2 hepatocellular carcinoma cells. FOXO3 transcription factors regulate target genes involved in apoptosis. H cordata significantly increased the mRNA and protein expression of HIF-1A and FOXO3 and stimulated MEF2A expression in addition to increased apoptosis in HepG2 cells within 24 hours. Therefore, we determined the potential role of FOXO3 on apoptosis and on H cordata–induced MEF2A in HepG2 cells. HIF-1A silencing by siRNA attenuated MEF2A and H cordata–mediated FOXO3 upregulation in HepG2 cells. Furthermore, H cordata–mediated MEF2A expression enhanced caspase-3 and caspase-7, which were abolished on silencing FOXO3 with siRNA. In addition, H cordata inhibited growth of human hepatocellular carcinoma xenografts in nude mice. Taken together, our results demonstrate that H cordata enhances HIF-1A/FOXO3 signaling, leading to MEF2A upregulation in HepG2 cells, and in parallel, it disturbs the expression of Bcl-2 family proteins (Bax, Bcl-2, and Bcl-xL), which results in apoptosis. Taken together, these findings demonstrate that H cordata promotes the activation of HIF-1A–FOXO3 and MEF2A pathways to induce apoptosis in human HepG2 hepatocellular carcinoma cells and is, therefore, a promising candidate for antitumor drug development.
Previously, the arginine at hen egg-white lysozyme 61 (HEL 61) was characterized as inhibiting T-lymphocyte stimulation due to the inefficient binding of the arginine-containing epitope peptide to the corresponding major histocompatibility complex class II molecules in C57BL/6 mice. In this study, we produced recombinant HEL, with arginine or alanine at HEL 61, and compared its ability to induce immune responses in mice to see whether modification of an inhibitory amino acid could enhance the immunogenicity of an inefficient antigen. Immunization of the mice with modified HEL induced strong antibody and T-cell immune responses against the native antigen. The enhanced T-cell immune response was due to a more specific elevation of the T-cell responses to the HEL 46-61 epitope region than to other epitope regions, although recognition of the other epitope peptides of HEL was generally increased. Mass spectrometric analyses of the epitope peptides generated by splenic antigen-presenting cells indicated that production of the epitope peptides encompassing HEL 46-61 was efficient using the modified antigen. These results suggest that modification of the critical amino acid residue(s) involved in hampering induction of an efficient immune response is an effective method to improve the immunogenicity of an inefficient antigen.
Summary To understand the mechanism of autoimmunity induction, hen egg lysozyme (HEL)‐transgenic (Tg) C57BL/6 (B6) mice were immunized with HEL or phosphorylcholine‐conjugated HEL (PC‐HEL). Repeated immunization of HEL‐Tg mice with native HEL failed to induce the antibody response against HEL. However, immunization with PC‐HEL generated a significant anti‐HEL antibody response. Immunization of the Tg mice with dominant (HEL74−88) or cryptic (HEL47−61) T‐cell epitope peptide stimulated the corresponding T‐cell response and similarly yielded the anti‐HEL antibody response. Predominance of immunoglobulin G1 (IgG1) anti‐HEL antibody response in the HEL‐Tg mice and preferential IL‐4 production by HEL‐specific T cells suggested the dependency of the antibody response to the presence of T helper 2. HEL‐Tg mice received HEL‐primed B6 T cells, but not HEL‐primed Tg T cells, were able to generate anti‐HEL antibody response following PC‐HEL immunization. The pattern and the level of epitope peptides generated by splenic antigen‐presenting cells indicated that PC‐HEL results in much more efficient processing as compared to HEL. These results strongly suggest that the enhancement of antigen processing by hapten (PC) conjugation to the antigen facilitates more efficient stimulation of T cells reactive to self antigen, HEL in HEL‐Tg mice resulting in the production of anti‐self HEL antibody.
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