Both the hyperproduction of oxygen free radicals (OFR) and the weakening of natural scavenging mechanisms have been implicated as contributors to multiple organ failure in septic shock. This study ...examined whether the antioxidants glutathione (GSH) and N-acetyl-L-cysteine (NAC) play a protective role against damage by OFR in early septic shock. We randomly entered 30 patients with septic shock into one of three groups within 24 h of diagnosis. All of the patients received septic shock therapy, including parenteral nutrition, antibiotics, and volume-expanding and inotropic agents. One group (Group B) also received 70 mg/kg/d of intravenous GSH, and a second group (Group C), 70 mg/kg/d of intravenous GSH and 75 mg/kg/d of intravenous NAC. The protection against OFR damage was evaluated by measuring expired ethane, plasma malondialdehyde, erythrocyte deformability, complement activation, and clinical scores at admission and on Days 3 and 5 of treatment. A significant decrease in peroxidative indexes was observed at Day 5 in Group B as compared with both the control group and basal values. The decrease in peroxidative indexes was even more marked in Group C. Clinical scores in this group were also significantly improved. In conclusion, the administration of high doses of NAC added to GSH significantly decreased the peroxidative stress of patients with septic shock.
Abstract Background Estrogens may induce the proliferation of neoplastic cells by activating neo-angiogenesis. Aim To evaluate the effect of estrogens on the expression of vascular endothelial growth ...factor (VEGF) and related receptors (VEGF-R) in human cholangiocarcinoma and the role played by VEGF in mediating the proliferative effects of estrogens. Methods Seven biopsies of intra-hepatic cholangiocarcinoma and the HuH-28 cell lines were investigated. Cell proliferation was measured by both PCNA Western blot and MTS proliferation assay. Results By immunohistochemistry, biopsies of human cholangiocarcinoma stained positively for VEGF-A and VEGF-C and related receptors. HuH-28 cells expressed VEGF-A, -C, and VEGFR-1, -2, -3 and, their protein level was enhanced by 17β-estradiol in association with the stimulation of cell proliferation. 17β-Estradiol-stimulated proliferation of HuH-28 cells was blocked by 70% by VEGF-TRAP, a receptor-based VEGF inhibitor. 17β-Estradiol induced the secretion of VEGF in the supernatant of HuH-28 cells. The stimulatory effect of 17β-estradiol on the protein expression of VEGF-A, VEGF-C and VEGFR-1, -2, -3 was blocked by antagonists of ER (Ici182,780) or insulin-like growth factor 1-receptor (αIR3). Conclusions With the limitations of experiments performed in a cell line, our study indicates that VEGF plays a major role in mediating the proliferative effects of estrogens on human cholangiocarcinoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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