• Title/Summary/Keyword: Physiology Health

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Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites

  • Choi, Sun-Hye;Lee, Byung-Hwan;Kim, Hyeon-Joong;Jung, Seok-Won;Kim, Hyun-Sook;Shin, Ho-Chul;Lee, Jun-Hee;Kim, Hyoung-Chun;Rhim, Hyewhon;Hwang, Sung-Hee;Ha, Tal Soo;Kim, Hyun-Ji;Cho, Hana;Nah, Seung-Yeol
    • Molecules and Cells
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    • v.37 no.9
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    • pp.656-663
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    • 2014
  • Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits $[Ca^{2+}]_i$ transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier $K^+$ ($I_{Ks}$) channel is a cardiac $K^+$ channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating $I_{Ks}$ channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human $I_{Ks}$ channel activity by expressing human $I_{Ks}$ channels in Xenopus oocytes. We found that gintonin enhances $I_{Ks}$ channel currents in concentration- and voltage-dependent manners. The $EC_{50}$ for the $I_{Ks}$ channel was $0.05{\pm}0.01{\mu}g/ml$. Gintonin-mediated activation 1 of the $I_{Ks}$ channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an $IP_3$ receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the $I_{Ks}$ channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 $[Ca^{2+}]_i$/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on $I_{Ks}$ channel. However, gintonin had no effect on hERG $K^+$ channel activity. These results show that gintonin-mediated enhancement of $I_{Ks}$ channel currents is achieved through binding of the $[Ca^{2+}]_i$/CaM complex to the C terminus of KCNQ1 subunit.

Phorbol Ester-induced Contraction Through p38 Mitogen-activated Protein Kinase is Diminished in Aortas from DOCA-Salt Hypertensive Rats

  • Lee, Chang-Kwon;Kim, Jung-Kwan;Won, Kyung-Jong;Lee, Hwan-Myung;Kim, Hyo-Jin;Roh, Hui-Yul;Park, Hyo-Jun;Shin, Hwa-Sup;Park, Tae-Kyu;Kim, Bo-Kyung;Lee, Sang-Mok
    • Archives of Pharmacal Research
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    • v.29 no.11
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    • pp.1024-1031
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    • 2006
  • The role of mitogen-activated protein kinase (MAPK) in the decreased contractile response to phorbol ester in aortic smooth muscle strips from deoxycorticosterone acetate (DOCA)-salt hypertensive rats was examined. Norepinephrine (NE) evoked greater contractility in aortic strips from DOCA rats than in those of sham-operated rats. 12-Deoxyphorbol 13-isobutyrate (DPB) induced contraction in $Ca^{2+}-free$ medium, which was diminished in strips from DOCA rats compared to sham-operated rats. Vasoconstrictions induced by these stimulants were inhibited by SB203580 and PD098059, inhibitors of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2, respectively, in both strips. The phosphorylation of p38 MAPK and ERK1/2 induced by NE was greater in strips from DOCA rats compared to those from sham-operated rats, and this phosphorylation was inhibited by the kinase inhibitors. DPB increased the phosphorylation of p38 MAPK and ERK1/2 in strips from both animals, and the increment of p38 MAPK phosphorylation by the stimulant was diminished in strips from DOCA rats compared to sham-operated rats. These findings suggest that the $Ca^{2+}-independent$ contraction evoked by DPB results from the activation of MAPKs in rat aortic smooth muscle and that the attenuated contractility by DPB in DOCA rat appears to be associated with diminished p38 MAPK activity.

Fuctional Relationship between Rate of Fatty Acid Oxidation and Carnitine Palmitoyl Transferase I Activity in Various Rat Tissues

  • Cho, Yu-Lee;Do, Kyung-Oh;Kwon, Tae-Dong;Jang, Eung-Chan;Lee, Keun-Mi;Lee, Suck-Kang;Kim, Jong-Yeon
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.4
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    • pp.207-210
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    • 2003
  • Lipids play many structural and metabolic roles, and dietary fat has great impact on metabolism and health. Fatty acid oxidation rate is dependent on tissue types. However there has been no report on the relationship between the rate of fatty acid oxidation and carnitine transport system in outer mitochondrial membrane of many tissues. In this study, the rate of fatty acid oxidation and carnitine palmitoyltransferase (CPT) I activity in the carnitine transport system were measured to understand the metabolic characteristics of fatty acid in various tissues. Palmitic acid oxidation rate and CPT I activity in various tissues were measured. Tissues were obtained from the white and red skeletal muscles, heart, liver, kidney and brain of rats. The highest lipid oxidation rate was demonstrated in the cardiac muscle, and the lowest oxidation rate was in brain. Red gastrocnemius muscle followed to the cardiac muscle. Lipid oxidation rates of kidney, white gastrocnemius muscle and liver were similar, ranging from 101 to 126 DPM/mg/hr. CPT I activity in the cardiac muscle was the highest, red gastrocnemius muscle followed by liver. Brain tissue showed the lowest CPT I activity as well as lipid oxidation rate, although the values were not significantly different from those of kidney and white gastrocnemius muscle. Therefore, lipid oxidation rate was highly (p<0.001) related to CPT I activity. Lipid oxidation rate is variable, depending on tissue types, and is highly (p<0.001) related to CPT I activity. CPT I activity may be a good marker to indicate lipid oxidation capacity in various tissues.

Tissue Microarrays in Biomedical Research

  • Chung, Joon-Yong;Kim, Nari;Joo, Hyun;Youm, Jae-Boum;Park, Won-Sun;Lee, Sang-Kyoung;Warda, Mohamad;Han, Jin
    • Bioinformatics and Biosystems
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    • v.1 no.1
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    • pp.28-37
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    • 2006
  • Recent studies in molecular biology and proteomics have identified a significant number of novel diagnostic, prognostic, and therapeutic disease markers. However, validation of these markers in clinical specimens with traditional histopathological techniques involves low throughput and is time consuming and labor intensive. Tissue microarrays (TMAs) offer a means of combining tens to hundreds of specimens of tissue onto a single slide for simultaneous analysis. This capability is particularly pertinent in the field of cancer for target verification of data obtained from cDNA micro arrays and protein expression profiling of tissues, as well as in epidemiology-based investigations using histochemical/immunohistochemical staining or in situ hybridization. In combination with automated image analysis, TMA technology can be used in the global cellular network analysis of tissues. In particular, this potential has generated much excitement in cardiovascular disease research. The following review discusses recent advances in the construction and application of TMAs and the opportunity for developing novel, highly sensitive diagnostic tools for the early detection of cardiovascular disease.

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Dynamics of pre-shift and post-shift lung function parameters among wood workers in Ghana

  • John Ekman;Philip Quartey;Abdala Mumuni Ussif;Niklas Ricklund;Daniel Lawer Egbenya;Gideon Akuamoah Wiafe;Korantema Mawuena Tsegah;Akua Karikari;Hakan Lofstedt;Francis Tanam Djankpa
    • Annals of Occupational and Environmental Medicine
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    • v.35
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    • pp.39.1-39.14
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    • 2023
  • Background: Diseases affecting the lungs and airways contribute significantly to the global burden of disease. The problem in low- and middle-income countries appears to be exacerbated by a shift in global manufacturing base to these countries and inadequate enforcement of environmental and safety standards. In Ghana, the potential adverse effects on respiratory function associated with occupational wood dust exposure have not been thoroughly investigated. Methods: Sixty-four male sawmill workers and 64 non-woodworkers participated in this study. The concentration of wood dust exposure, prevalence and likelihood of association of respiratory symptoms with wood dust exposure and changes in pulmonary function test (PFT) parameters in association with wood dust exposure were determined from dust concentration measurements, symptoms questionnaire and lung function test parameters. Results: Sawmill workers were exposed to inhalable dust concentration of 3.09 ± 0.04 mg/m3 but did not use respirators and engaged in personal grooming habits that are known to increase dust inhalation. The sawmill operators also showed higher prevalence and likelihoods of association with respiratory symptoms, a significant cross-shift decline in some PFT parameters and a shift towards a restrictive pattern of lung dysfunction by end of daily shift. The before-shift PFT parameters of woodworkers were comparable to those of non-woodworkers, indicating a lack of chronic effects of wood dust exposure. Conclusions: Wood dust exposure at the study site was associated with acute respiratory symptoms and acute changes in some PFT parameters. This calls for institution and enforcement of workplace and environmental safety policies to minimise exposure at sawmill operating sites, and ultimately, decrease the burden of respiratory diseases.

Comparing the Performance of Three Severity Scoring Systems for ICU Patients: APACHE III, SAPS II, MPM II (중환자 중증도 평가도구의 타당도 평가 - APACHE III, SAPS II, MPM II)

  • Kwon, Young-Dae;Hwang, Jeong-Hae;Kim, Eun-Kyung
    • Journal of Preventive Medicine and Public Health
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    • v.38 no.3
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    • pp.276-282
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    • 2005
  • Objectives : To evaluate the predictive validity of three scoring systems; the acute physiology and chronic health evaluation(APACHE) III, simplified acute physiology score(SAPS) II, and mortality probability model(MPM) II systems in critically ill patients. Methods : A concurrent and retrospective study conducted by collecting data on consecutive patients admitted to the intensive care unit(ICU) including surgical, medical and coronary care unit between January 1, 2004, and March 31, 2004. Data were collected on 348 patients consecutively admitted to the ICU(aged 16 years or older, no transfer, ICU stay at least 8 hours). Three models were analyzed using logistic regression. Discrimination was assessed using receiver operating characteristic(ROC) curves, sensitivity, specificity, and correct classification rate. Calibration was assessed using the Lemeshow-Hosmer goodness of fit H-statistic. Results : For the APACHE III, SAPS II and MPM II systems, the area under the receiver operating characterist ic(ROC) curves were 0.981, 0.978, and 0.941 respectively. With a predicted risk of 0.5, the sensitivities for the APACHE III, SAPS II, and MPM II systems were 81.1, 79.2 and 71.7%, the specificities 98.3, 98.6, and 98.3%, and the correct classification rates 95.7, 95.7, and 94.3%, respectively. The SAPS II and APACHE III systems showed good calibrations(chi-squared H=2.5838 p=0.9577 for SAPS II, and chi-squared H=4.3761 p=0.8217 for APACHE III). Conclusions : The APACHE III and SAPS II systems have excellent powers of mortality prediction, and calibration, and can be useful tools for the quality assessment of intensive care units(ICUs).

Electrically-evoked Neural Activities of rd1 Mice Retinal Ganglion Cells by Repetitive Pulse Stimulation

  • Ryu, Sang-Baek;Ye, Jang-Hee;Lee, Jong-Seung;Goo, Yong-Sook;Kim, Chi-Hyun;Kim, Kyung-Hwan
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.6
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    • pp.443-448
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    • 2009
  • For successful visual perception by visual prosthesis using electrical stimulation, it is essential to develop an effective stimulation strategy based on understanding of retinal ganglion cell (RGC) responses to electrical stimulation. We studied RGC responses to repetitive electrical stimulation pulses to develop a stimulation strategy using stimulation pulse frequency modulation. Retinal patches of photoreceptor-degenerated retinas from rd1 mice were attached to a planar multi-electrode array (MEA) and RGC spike trains responding to electrical stimulation pulse trains with various pulse frequencies were observed. RGC responses were strongly dependent on inter-pulse interval when it was varied from 500 to 10 ms. Although the evoked spikes were suppressed with increasing pulse rate, the number of evoked spikes were >60% of the maximal responses when the inter-pulse intervals exceeded 100 ms. Based on this, we investigated the modulation of evoked RGC firing rates while increasing the pulse frequency from 1 to 10 pulses per second (or Hz) to deduce the optimal pulse frequency range for modulation of RGC response strength. RGC response strength monotonically and linearly increased within the stimulation frequency of 1~9 Hz. The results suggest that the evoked neural activities of RGCs in degenerated retina can be reliably controlled by pulse frequency modulation, and may be used as a stimulation strategy for visual neural prosthesis.

Study on the Interrelationship of the Preventive Public-health and the Classification on the Body Form's Type (안면형태(顔面形態) 유형분류(類型分類)에 근거한 “치미병(治未病)” 예방의학정신과의 상관성에 대한 연구)

  • Lee, Jeong-Won;Kim, Hoon;Shin, Soon-Shik;Lee, Hai-Woong;Lee, Yong-Tae;Kim, Gyeong-Cheol
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.1
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    • pp.194-198
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    • 2008
  • The treatment before growing into disease is the highest level of the spirit of oriental preventive public medicine. Specially the treatmentt is very important in the life style disease of the aged society, and it is closely connected the human body-form diagnosis reflecting the character of individual physiology and pathology. The human body-form diagnosis explain systematically the color of face, the form and movement of the body, the smell and the taste, the mentality, many or few of $Yin{\cdot}Yang$, the state of pulse, the Meridian, the state of pathology and the direction of the treatment, and therefore the human body-form diagnostis method has also the practical ity on classifying the type. As the spirit of oriental preventive public medicine is based on the Meridian control method and food cooking control method, it has an important effect on the general management of the disease, the making on the beautiful face and the healthy body, the prolongation of life, the management of the individual-ordered health.

Effects of exercise on AKT/PGC1-α/FOXO3a pathway and muscle atrophy in cisplatin-administered rat skeletal muscle

  • Bae, Jun Hyun;Seo, Dae Yun;Lee, Sang Ho;Shin, Chaeyoung;Jamrasi, Parivash;Han, Jin;Song, Wook
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.6
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    • pp.585-592
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    • 2021
  • Cisplatin has been reported to cause side effects such as muscle wasting in humans and rodents. The physiological mechanisms involved in preventing muscle wasting, such as the regulation of AKT, PGC1-α, and autophagy-related factor FOXO3a by MuRF 1 and Atrogin-1, remain unclear following different types of exercise and in various skeletal muscle types. Eight-week-old male Wistar rats (n = 34) were assigned to one of four groups: control (CON, n = 6), cisplatin injection (1 mg/kg) without exercise (CC, n = 8), cisplatin (1 mg/kg) + resistance exercise (CRE, n = 9) group, and cisplatin (1 mg/kg) + aerobic exercise (CAE, n = 11). The CRE group performed progressive ladder exercise (starting with 10% of body weight on a 1-m ladder with 2-cm-interval grids, at 85°) for 8 weeks. The CAE group exercised by treadmill running (20 m/min for 60 min daily, 4 times/week) for 8 weeks. Compared with the CC group, the levels of the autophagy-related factors BNIP3, Beclin 1, LC3-II/I ratio, p62, and FOXO3a in the gastrocnemius and soleus muscles were significantly decreased in the CRE and CAE groups. The CRE and CAE groups further showed significantly decreased MuRF 1 and Atrogin-1 levels and increased phosphorylation of AKT, FOXO3a, and PGC1-α. These results suggest that both ladder and aerobic exercise directly affected muscle wasting by modulating the AKT/PGC1-α/FOXO3a signaling pathways regardless of the skeletal muscle type.