• The Korean Journal of Pain
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• v.29 no.4
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• pp.229-238
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• 2016

Background: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. Methods: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ($[Ca^{2+}]_i$) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. Results: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in $[Ca^{2+}]_i$. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. Conclusions: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.

• BMB Reports
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• v.34 no.3
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• pp.237-243
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• 2001

Taxol, a natural product extracted from the Taxus brevifolia, is known to have significant anti-tumor activities against many common cancers, including ovarian and breast cancers. Despite the pronounced anti-tumor activity of this compound, its poor solubility in aqueous solutions hampers its clinical applications. We studied the anticancer mechanisms of the water-soluble taxol diethylenetriamine pentaacetate (DTPA) used for radiolabeling, and compared it to that of taxol. In vitro cytotoxicities of taxol and taxol-DTPA conjugate were tested in HT29 human colorectal cancer cells by the MTT method. As the result, the $IC_{50}$ value of the taxol-DTPA conjugate was about three fold higher than that of taxol. When analyzed by an agarose gel electrophoresis, the DNA ladders became evident after the incubation of cells with the taxol-DTPA conjugate for 24 h. We also found morphological changes of the cells undergoing apoptosis with electron microscopy Next, we examined the signal pathway of taxol-DTPA conjugate-induced apoptosis in HT29 cells. The activation of extracellular signal-regulated protein kinase (ERK1/2) occurred at 10, 30, 60 and 120 min after 200 nM taxol-DTPA conjugate treatment. The pretreatment of the MEK inhibitor (PD98059) completely blocked the taxol-DTPA conjugate-induced ERK1/2 activation. The activated ERK1/2 translocated into the nucleus at the same time and phosphorylated its transcriptional factor, c-Jun. These results suggest that the taxol-DTPA conjugate has an apoptotic activity in HT29 cells, and that its proapoptic activity might be related with the signal transduction via ERK1/2 and c-Jun similar to that of taxol.

• Journal of Animal Science and Technology
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• v.51 no.3
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• pp.217-224
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• 2009

This study was carried out to investigate the nutritional value of soybean meal (SBM) from various geographic origins and the effects of their dietary supplementation on performance of broiler chickens. Nutritional value of dehulled SBM originating from USA, and non-dehulled SBM from India (IND), Argentina (ARG) and Korea (KOR) were evaluated by analyzing chemical composition, urease activity (UA) and KOH solubility, and determining true metabolizable energy (TME), nitrogen corrected TME (TMEn) and true amino acid availability (TAAA). The contents of crude protein ranged from 45.43% (ARG) to 48.47% (USA) and those of crude fiber varied widely from 3.48% (USA) to 7.12% (IND). The measurements of lysine varied from 2.79% (IND) to 3.09% (USA) and those of methionine from 0.56% (IND) to 0.65% (USA). The values of TMEn varied from 2986.6 kcal/kg (IND) to 3228.9 kcal/kg (USA) and the averages of TAAA were from 91.61% (IND) to 92.27% (USA). UA was found to be from 0.02 (ARG) to 0.04 (KOR, USA) and those of KOH solubility from 73% (ARG) to 84% (USA). A total of four hundred 20-days-old male broiler chicks were divided into four groups and fed with isocaloric and isonitrogenous experimental diets containing 27.5% of SBM and same amounts of lysine and sulfur amino acids for 15 days. Final body weight and body weight gain were the highest in birds fed with SBM from USA and lowest in birds fed with SBM from IND although the differences were not statistically significant. The feed/gain in chicks fed diet containing SBM from USA was significantly improved (p<0.05) compared to those of the other groups. There were no significant differences in carcass characteristics and the concentration of total cholesterol in serum among the treatments. The results of in vitro assay and bioassay agreed with the performance of broiler chicks, and thus there were close correlation between the broiler performance and the measured nutritive values of SBM. In conclusion, dehulled SBM from USA was superior to non- dehulled SBM from ARG and IND with regard to nutritive values.