• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1123-1127
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• 2015

Uterine leiomyomas (ULM), are benign tumors of the smooth muscle cells of the myometrium. They represent a common health problem and are estimated to be present in 30-70% of clinically reproductive women. Abnormal angiogenesis and vascular-related growth factors have been suggested to be associated with ULM growth. The angiotensin-I converting enzyme (ACE) is related with several tumors. The aim of this study was to identify possible correlation between ULM and the ACE I/D polymorphism, to evaluate whether the ACE I/D polymorphism could be a marker for early diagnosis and prognosis. ACE I/D was amplified with specific primer sets recognizing genomic DNA from ULM (n=72) and control (n=83) volunteers and amplicons were separated on agarose gels. The observed genotype frequencies were in agreement with Hardy-Weinberg equilibrium ($x^2=2.162$, p=0.339). There was no association between allele frequencies and study groups ($x^2=0.623$; p=0.430 for ACE I allele, $x^2=0.995$; p=0.339 for ACE D allele). In addition, there were no significant differences between ACE I/D polymorphism genotype frequencies and ULM range in size and number ($X^2=1.760;$ p=0.415 for fibroid size, $X^2=0.342;$ p=0.843 for fibroid number). We conclude that the ACE gene I/D polymorphism is not related with the size or number of ULM fibroids in Turkish women. Thus it cannot be regarded as an early diagnostic parameter nor as a risk estimate for ULM predisposition.

• Journal of Korean Physical Therapy Science
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• v.13 no.2
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• pp.99-119
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• 2006

Endothelin (ET) is a 21 amino acid peptide with multifunctional effects on the vasculature as well as a variety of other cell types such as respiratory, gastrointestinal, urogenital, endocrine, central nervous systems, and others. Endothelin has emerged as a modulator by autocrine and paracrine actions for many cellular activities, including vasoconstriction, cell proliferation, hormone production, neurotransmitter and/or neuromodulator. The endothelin family consists of three closely related peptides, ET-1, ET-2, and ET-3 derived from separate genes, such as chromosome 6, 1, and 20, respectively. ET-1 is the predominant isoform produced in the cardiovascular system and about which most is known. Endothelin receptors are seven-transmembrane GTP-binding protein-coupled receptors, which are classified into endothelin-A (ETA) and endothelin-B (ETB) receptors. Interestingly, recent evidence is accumulating to suggest that ET -1 may contribute to a variety of pain states such as allodynia and hyperalgesia in animals and humans. Therefore, in this review the biological characteristics and contraction-related mechanism of endothelin-1 in mammalian cells will be summarized. Especially, we focus on multifunctional roles for ET-1 in noxious stimulation-induced pain for the study of pain specialized physical therapy.

• Journal of Chest Surgery
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• v.36 no.12
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• pp.887-893
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• 2003

External stimuli increases intracellular (IC) $Ca^{2+}$, which increases extracellular (EC) $K^{+}$. To verify $K^{+}$ effects on the vascular contraction, we performed an experiment using mouse aortic endothelial cell. Meterial and Method: We examined the mouse aortic contractility changes as we measured the IC $Ca^{2+}$ change and ionic current by using the voltage clamp technique under different conditions such as: increasing EC $K^{+}$, removing endothelial cell, giving L-NAME (N-nitro-L-arginine methyl ester) which suppress nitric oxide formation, Ouabain which control N $a^{+}$ - $K^{+}$ pump and N $i^{2+}$ which repress N $a^{+}$-C $a^{2+}$ exchanger Result: When we increased EC $K^{+}$ from 6 to 12 mM, there was no change in aortic contractility. Aorta contracted with more than 12 mM of EC $K^{+}$. Ace-tylcholine (ACh) induced relaxation was inhibited with EC $K^{+}$ from 6 to 12 mM, but was not found after de-endothelialization or L-NAME treatment. ATP or ACh increased IC $Ca^{2+}$ in cultured endothelium. After maximal increase of IC $Ca^{2+}$, increasing EC $K^{+}$ from 6 to 12 mM made IC $Ca^{2+}$ decrease and re-decreasing EC $K^{+}$ to 6 mM made IC $Ca^{2+}$ increase. Ouabain and N $i^{2+}$ masked the inhibitory effect of endothelium dependent relaxation by increased EC $K^{+}$. Conclusion: These data indicate that increase in EC $K^{+}$ relaxes vascular smooth muscle and reduces $Ca^{2+}$ in the endothelial cells which inhibit endothelium dependent relaxation. This inhibitory mechanism may be due to the activation of N $a^{+}$- $K^{+}$ pump and N $a^{+}$-C $a^{2+}$ exchanger. $a^{+}$-C $a^{2+}$ exchanger.r.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.1
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• pp.32-39
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• 2018

Objective: In this study, we investigated the adverse effects of dietary zearalenone (ZEA) (0.5 to 1.5 mg/kg diet) on the localization and expression of the growth hormone receptor (GHR) in the uteri of post-weaning gilts and explored alternative mechanism of the reproductive toxicity of ZEA on piglets. Methods: A total of forty healthy piglets (Duroc${\times}$Landrace${\times}$Large White) aged 28 d were selected for study. Piglets were transferred to single cages after 10 days' adaptation on an obstetric table. The animals were allocated to one of four treatments: a normal basal diet supplemented with 0 (Control), 0.5 (ZEA0.5), 1.0 (ZEA1.0), or 1.5 (ZEA1.5) mg/kg purified ZEA, and fed for 35 d after the 10-d adaptation. Analyzed ZEA concentrations in the diets were 0, $0.52{\pm}0.07$, $1.04{\pm}0.03$, and $1.51{\pm}0.13mg/kg$, respectively. At the end of the feeding trial, piglets were euthanized after being fasted for 12 h. Two samples of uterine tissue from each pig were rapidly collected, one of which was stored at $-80^{\circ}C$ for analysis of the relative mRNA and protein expression of GHR, and the second was promptly fixed in Bouin's solution for immunohistochemical analysis. Results: The relative weight of the uteri and thickness of the myometrium and endometrium increased linearly (p<0.001) and quadratically (p<0.001) with an increasing level of ZEA. The results of immunohistochemical analysis indicated that GHR immunoreactive substance was mainly localizated in the cytoplasm of uterine smooth muscle, glandular epithelial, luminal epithelial, stromal, and vascular endothelial cells. In contrast, nuclear staining was rarely observed. The immunoreactive integrated optic density of GHR in the myometrium, luminal epithelium, glandular epithelium, and whole uteri of weaning gilts increased linearly (p<0.001) and quadratically (p<0.05) with an increasing level of ZEA. The mRNA and protein expression of GHR in the uteri of weaning gilts increased linearly (p<0.001) and quadratically (p<0.05) with an increasing level of ZEA. Conclusion: In conclusion, ZEA at a concentration of 0.5 mg/kg was sufficient to significantly thicken the myometrium and endometrium, and at a concentration of 1.0 mg/kg induced a high level of GHR expression to promote growth and development of the uteri. This revealed an alternative molecular mechanism whereby ZEA induces growth and development of the uteri and provides a theoretical basis for the revision of Chinese feed hygiene standards.