• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.419-425
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• 2010

Mast cells are activated by specific allergens and also by various nonspecific stimuli, which might induce physical urticaria. This study investigated the functional expression of temperature sensitive transient receptor potential vanilloid (TRPV) subfamily in the human mast cell line (HMC-1) using whole-cell patch clamp techniques. The temperature of perfusate was raised from room temperature (RT, $23{\sim}25^{\circ}C$) to a moderately high temperature (MHT, $37{\sim}39^{\circ}C$) to activate TRPV3/4, a high temperature (HT, $44{\sim}46^{\circ}C$) to activate TRPV1, or a very high temperature (VHT, $53{\sim}55^{\circ}C$) to activate TRPV2. The membrane conductance of HMC-1 was increased by MHT and HT in about 50% (21 of 40) of the tested cells, and the I/V curves showed weak outward rectification. VHT-induced current was 10-fold larger than those induced by MHT and HT. The application of the TRPV 4 activator $3{\alpha}$-phorbol 12,13-didecanoate ($4{\alpha}$ PDD, $1\;{\mu}M$) induced weakly outward rectifying currents similar to those induced by MHT. However, the TRPV3 agonist camphor or TRPV1 agonist capsaicin had no effect. RT-PCR analysis of HMC-1 demonstrated the expression of TRPV4 as well as potent expression of TRPV2. The $[Ca^{2+}]_c$ of HMC-1 cells was also increased by MHT or by $4{\alpha}$ PDD. In summary, our present study indicates that HMC-1 cells express $Ca^{2+}$-permeable TRPV4 channels in addition to the previously reported expression of TRPV2 with a higher threshold of activating temperature.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.25-32
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• 2014

Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. NO is produced by nitric oxide synthase (NOS), and NOS is abundantly expressed in the human dental pulp cells (HDPCs). NO produced by NOS can be cytotoxic at higher concentrations to HDPCs. However, the mechanism by which this cytotoxic pathway is activated in cells exposed to NO is not known. The purpose of this study was to elucidate the NO-induced cytotoxic mechanism in HDPCs. Sodium nitroprusside (SNP), a NO donor, reduced the viability of HDPCs in a dose- and time-dependent manner. We investigated the in vitro effects of nitric oxide on apoptosis of cultured HDPCs. Cells showed typical apoptotic morphology after exposure to SNP. Besides, the number of Annexin V positive cells was increased among the SNP-treated HDPCs. SNP enhanced the production of reactive oxygen species (ROS), and N-acetylcysteine (NAC) ameliorated the decrement of cell viability induced by SNP. However, a soluble guanylate cyclase inhibitor (ODQ) did not inhibited the decrement of cell viability induced by SNP. SNP increased cytochrome c release from the mitochondria to the cytosol and the ratio of Bax/Bcl-2 expression levels. Moreover, SNP-treated HDPCs elevated activities of caspase-3 and caspase-9. While pretreatment with inhibitors of caspase (z-VAD-fmk, z-DEVD-fmk) reversed the NO-induced apoptosis of HDPCs. From these results, it can be suggested that NO induces apoptosis of HDPCs through the mitochondria-dependent pathway mediated by ROS and Bcl-2 family, but not by the cyclic GMP pathway.

• The Korean Journal of Physiology
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• v.23 no.1
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• pp.23-34
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• 1989

Gentamicin (GM) is a polybasic, aminoglycoside antibiotic used frequently for the treatment of serious gram-negative infections. The major limiting factors in the clinical use of GM as well as other aminoglycoside antibiotics are their nephrotoxicity and ototoxicity. The primary mechanism of cell injury in aminoglycoside toxicity appears to be the disruption of normal membrane function and the inhibition of $Na^{+}-K^{+}$ ATPase activity. There are both indirect and direct evidences which suggests that the effect of aminoglycoside antibiotics on $Na^{+}-K^{+}$ ATPase may explain, or contribute to, their toxicity. It has been shown that aminoglycoside reduce total ATPase activity (Kaku et al., 1973) and $Na^{+}-K^{+}$ ATPase activity (linuma et al., 1967) in the stria vascularis and spiral ligament of the guinea-pig cochlea. Lipsky and Lietman (1980) reported that aminoglycoside antibitoics inhibited the activity of $Na^{+}-K^{+}$ ATPase in microsomal fractions of the cortex and medulla of the guinea-pig kidney, isolated rat renal tubule and human erythrocyte ghosts. The present invstigation was undertaken to elucidate the mechanism of GM on human erythrocytes by examining its effect on $Na^{+}-K^{+}$ ATPase activity, actives sodium and potassium transport across red blood cell and $^{3}H-ouabain$ binding to red blood cell membranes. The results obtained are summarized as follows: 1) CM inhibited significantly both the activity of total ATPase and $Na^{+}-K^{+}$ ATPase at all concentrations tested. 2) GM inhibited active $^{22}Na$ efflux across red blood cell. When ouabain is present, the rate of $^{22}Na$ efflux was completely inhibited. When both GM and ouabain were added, the inhibitory effect of active $^{22}Na$ efflux was more pronounced. 3) Active $^{86}Rb$ influx was inhibited significantly by GM. In the presence of ouabain, the rate of $^{86}Rb$ influx is markedly inhibited. But $^{86}Rb$ influx is not appreciably altered by the presence of both GM and ouabain. 4) In the presence of GM, $^{3}H-ouabain$ binding to red blood cell membrane increased. From the above results, it may be concluded that the inhibition of active sodium and potassium transport across red blood cell by gentamicin appears to be due to the inhibition of $Na^{+}-K^{+}$ ATPase activity and an increase in ouabain binding to red blood cell membranes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.626-629
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• 2002

In Oriental medicine, Five Mental is a concept for understanding of man's mental structure. Spirit and body is inseparable relation in Oriental Medicine. Function of spirit and body is regarded as one in Oriental Medical physiology. Spirit is the essence of a function which an organism reveal, and it is regarded in the same with life. For this reason, identification spirit with life is special feature of Oriental Medicine. In Confucianism, Li(理) refers to nature's discipline, which everything under the sun shares. It is similar to the concept of Shin(神) in a broad sense and Sung(性) is similar to that of Shin(神) in a narrow sense. Confucianism's principle is similar to Oriental medicine's, in that they classify Sung(性) into Gi-Jil-Ji-Sung(氣質之性) and Bon-Yeon-Ji-Sung(本然之性), that Sung(性) acts upon man differently according to his disposition, and that materials have an effect on Shin(神)'s action. According to mind's action, there are Human mind(人心) and Moral mind(道心). Human mind(人心) is defined as a mental action of higher degree and Moral mind(道心) is conceived as a mental action related to body. It is similar to Oriental medicine's principle in which Shin(神) is classified into Hun(魂) and Beak(魄) according to its action. Yi(意) is self-control and application, and Zhi(志) is a conscious state in which basic acts towards the object are fixed regularly. Those are similar to the concepts of Oriental medicine.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.2
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• pp.131-135
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• 2005

Potassium channels in human skin fibroblast have been studied as a possible site of Alzheimer disease pathogenesis. Fibroblasts in Alzheimer disease show alterations in signal transduction pathway such as changes in $Ca^{2+}$ homeostasis and/or $Ca^{2+}-activated$ kinases, phosphatidylinositol cascade, protein kinase C activity, cAMP levels and absence of specific $K^+$ channel. However, little is known so far about electrophysiological and pharmacological characteristics of large-conductance $Ca^{2+}$-activated $K^+$ ($BK_{Ca}$) channel in human fibroblast (CRL-1474). In the present study, we found Iberiotoxin- and TEA-sensitive outward rectifying oscillatory current with whole-cell recordings. Single channel analysis showed large conductance $K^{+}$ channels (106 pS of chord conductance at +40 mV in physiological $K^+$ gradient). The 106 pS channels were activated by membrane potential and $[Ca^{2+}]_i$, consistent with the known properties of $BK_{Ca}$ channels. $BK_{Ca}$ channels in CRL-1474 were positively regulated by adenylate cyclase activator ($10{\mu}M$ forskolin), 8-Br-cyclic AMP ($300{\mu}M$) or 8-Br-cyclic GMP ($300{\mu}M$). These results suggest that human skin fibroblasts (CR-1474) have typical $BK_{Ca}$ channel and this channel could be modulated by c-AMP and c-GMP. The electrophysiological characteristics of fibroblasts might be used as the diagnostic clues for Alzheimer disease.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.3
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• pp.143-147
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• 2006

Carthamus tinctorius L.is known to improve fracture healing, and bone morphogenetic proteins (BMPs) are associated with the formation and healing process of bone. BMP-2 and BMP-7 are two of the most important BMPs during the bone healing process. Human osteosarcoma MG63 cells and rats were used to determine the effects of Carthamus tinctorius L. extract (CTE) on BMP-2 gene expression. BMP-2 gene expression by CTE treatment in human osteosarcoma MG63 cells was not different from the control group until 8 hours of incubation, but was significantly higher, by 31%, than that of the control group at 16 hr of incubation. Microscopic findings of the 9th rib 3 weeks after fracture showed typical rimming of the osteoblast and immature bone formation in control and CTE groups. BMP-2 gene expression by in situ hybridization was remarkably increased by a CTE-supplemented diet in the fracture group compared to the control group. In conclusion, Carthamus tinctorius L. increased BMP-2 gene expression in human osteosarcoma cells and fractured bone. But further studies would be needed to elucidate the effect of CTE on fracture healing in vivo because our results did not show any evidence of healing improvement histologically $3^{rd}$ week after fracture.

• International Journal of Oral Biology
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• v.34 no.2
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• pp.73-79
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• 2009

Cytosolic $Ca^{2+}$ is an important regulator of tumor cell proliferation and metastasis. Recently, the strategy of blocking receptors and channels specific to certain cancer cell types has emerged as a potentially viable future treatment. Oral squamous cell carcinoma is an aggressive form of cancer with a high metastasis rate but the receptor-mechanisms involved in $Ca^{2+}$ signaling in these tumors have not yet been elucidated. In our present study, we report that bradykinin induces $Ca^{2+}$ signaling and its modulation in the human oral squamous carcinoma cell line, HSC-3. Bradykinin was found to increase the cytosolic $Ca^{2+}$ levels in a concentration-dependent manner. This increase was inhibited by pretreatment with the phospholipase C-${\beta}$ inhibitor, U73122, and also by 2-aminoethoxydiphenyl borate, an inhibitor of the inositol 1,4,5-trisphosphate receptor. Pretreatment with extracellular ATP also inhibited the peak bradykinin-induced $Ca^{2+}$ rise. In contrast, the ATP-induced rise in cytosolic $Ca^{2+}$ was not affected by pretreatment with bradykinin. Pretreatment of the cells with either forskolin or phorbol 12-myristate 13-acetate (activators of adenylyl cyclase and protein kinase C, respectively) prior to bradykinin application accelerated the recovery of cytosolic $Ca^{2+}$ to baseline levels. These data suggest that bradykinin receptors are functional in $Ca^{2+}$ signaling in HSC-3 cells and may therefore represent a future target in treatment strategies for human oral squamous cell carcinoma.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.4
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• pp.571-579
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• 2010

The advancement of medical technology has made it possible to treat various incurable diseases. Especially organ transplantation can give another life to the patients who have organ failure and could not find any other ways to treat their diseases. According to the development of medical technology and immunosuppressive drugs, the rate and extent of organ transplantation is increasing these days. New medical technologies like organ transplantation brought on critical issues and these have changed the way of thinking and morals that has been the fundamental rules in our society. Bioethics is already an important field of medicine and oriental medicine should investigate the problem caused by the development of medical technology and life science and should form a view of life in oriental medicine. Oriental medicine is East Asian traditional medicine based on "Huangdi-Neijing", constructed by the system of Jangfu and meridian. The traditional therapies of oriental medicine have completed a scientific system on the point of view that looks on human and nature equally. This process continued to form a new medical theory as the environment was changed and the new diseases were appeared since "Huangdi-Neijing" and "Shoganron" showed a new scope to investigate human and diseases. Therefore, it is important to develop the point of view of oriental medicine as the medical situation was changed. Oriental medicine has a holistic view that considers human as a little cosmos resonated by a big cosmos and regards the possibility to recover and to regulate the energy in our body. This theory is a basic idea of oriental philosophy. Oriental medicine focuses on the balance of yin and yang of the body and tries to harmonize the imbalance of yin and yang caused by the life style and environment. This can solve many problems that cannot be settled by modern medicine and this can accomplish the new paradigm of oriental medicine that is needed these days.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.677-683
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• 2005

The aim of this study was to investigate the apoptotic effect and its mechanism on Radix Aconiti (RA) extract in HL-60 human leukemia cell line. RA extract induced apoptosis as confirmed by discontinuous fragmentation of DNA. To clarify the mechanisms on RA extract-induced apoptosis, we examined the caspase-3, -8 enzyme activity and protein levels including Fas, FasL in HL-60 cells. Treatment with RA extracts resulted in the increase of caspase-3 enzyme activity in a time and dose-dependent manners, which was accompanied by the cleavage of poly-(ADP-ribose) polymerase (PARP). This activation of caspase-3 enzyme resulted from cleavage of procaspase-8, which was followed by increases of FasL, Fas protein expression in RA extracts-treated HL-60 cells. In conclusion, RA extract induced apoptosis of HL-60 human leukemia cell line. This results suggest that the apoptotic mechanisms of RA extract on HL-60 cells involved in FasL, Fas activation, procaspase-8 cleavage, activation of caspase-3 and cleavage of PARP. Collectively, these results suggest that RA may be a valuable agent as a anti-cancer drug.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.3
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• pp.353-360
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• 2010

Huang di's Four Classics introduces the first full-scale Yin-Yang theory. The ancient idea of Yin-Yang could be classified systematically throughout Huang di's Four Classics and make itself the cause of creation, movement, and variation. The Tao of essence and Reason-Law(理法) is a single 'One'(一) and completes the reality of Tao adopting Yin-Yang as an elementary. The elementary of Yin-Yang has rules and laws and then the Tao manifest itself through Yin-Yang. The features of Yin-Yang theory in Huang di's Four Classics are placed on the explanation of the structure of the universe embodied as class and system. The class and system are the structured worlds in the space based on the upper and lower sides Yin-Yang idea(上下陰陽觀). It means the system by Yin-Yang theory, corresponding to the flat structure of the Sky and the Earth mentioned in Gaitian theory, one of the ancient theory of the universe structure. By adopting Huang di's Four Classics' Tian-zhi Yin-Yang theory(天地陰陽論) and developing the class system in human bodies, The Hwangjenegyeng appreciates human bodies as a whole. In addition, by applying Four seasons Yin-Yang theory not only to human bodies but also to the space of Liu-he(六合) and the time of Four Seasons(四時), it developed Yin-Yang theory of Huang di's Four Classics more abundantly and embodied Yin-Yang theory in many fields including physiology, pathology, diagnostics, and prescriptions.