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Pharmacokinetics Interaction between Cardiotonic Pills and Cilostazol in Rats (렛트를 이용한 심적환과 cilostazol에 관한 상호작용 연구)

  • Kim, Ekyune
    • Journal of Life Science
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    • v.26 no.1
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    • pp.123-128
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    • 2016
  • The object of this study was to obtain accurate information about the co-administration effects of cardiotonic pills on the pharmacokinetics of cilostazol were observed as a process of the comprehensive and integrative medicine. Cilostazol is a synthetic anti-platelet and vasodilator agent developed for the treatment of intermittent claudication resulting from peripheral arterial disease. By increasing intracellular cyclic adenosine monophosphate (cAMP), cilostazol induces the activation of protein kinase A, which activates endothelial nitric oxide synthase. In order to evaluate the effect of a single or repeated cardiotonic pill dose on the pharmacokinetics of cilostazol, a single dose of pure_distilled water or a colloidal suspension of distilled water and cardiotonic pills were administered to the control and test groups, respectively. After 30 min, both groups were administered cilostazol. Plasma was collected 30min before administration, and 0.25, 0.5, 0.45, 1, 2, 4, 6, 8, and 24h after the end of cilostazol treatment. We then evaluated the pharmacokinetic changes observed with cilostazol between the control and test groups. No statistically significant differences were observed. These findings demonstrated that a single dose of cardiotonic pills did not affect the pharmacokinetics of cilostazol. The results obtained in this study suggest that co-administration of cardiotonic pills and cilostazol may not affect the bioavailability of cilostazol as a potential drug interaction.

Detection for Multiresidue of the Organophosphorus and Carbamate Pesticides by Enzyme-Inhibition Method (효소 저해법을 이용한 유기인계 및 Carbamate계 농약의 다성분 잔류 검출)

  • 김정호
    • Environmental Analysis Health and Toxicology
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    • v.17 no.3
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    • pp.265-272
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    • 2002
  • This study was carried out with the detection for multiresidue of the organophosphorus pesticides such as malathion, parathion. diazinon, and carbamate pesticide such as carbaryl, by enzyme-inhibition method. The acetylcholinesterase (AChE) and cholinesterase (ChE) activities in chicken brain determined by the Ellman's method were 166.6 and 5.8 $\mu$mol/min/g protein, and in chicken plasma were 23.1 and 8.3 $\mu$mol/min/g protein, respectively. The optimum pH of AChE and ChE was 8.2 and 7.8, respectively. The Km of AChE and ChE was 0.034 and 0.045 mM, respectively. I$\_$50/ for AChE and ChE by some organophosphorus was 55.82 and 99.42 mg/L of malathion, 31.16 and 29.13 mg/L of parathion, and 17.89 and 19.62 mg/L of diazinon, respectively. I$\_$50/ for AChE and ChE by carbaryl of carbamate was 0.10 and 0.05 mg/L, respectively. The 0.07 mg/L of drinking water advisory level for carbaryl could be detected with I$\_$50/ of AChE and ChE. Enzyme-Inhibition (EI) method with AChE and ChE was used the multiresidue method to detect the 1 mg/L of the carbamate pesticides.

Effect of Kami-kanghwalsan (KKHS) on Atopic Dermatitis-like Skin Lesions Induced in NC/Nga Mouse by Mite Antigen Stimulation (가미강활산(加味羌活散)이 집먼지 진드기 추출물로 유도된 NC/Nga mouse의 아토피 피부염에 미치는 영향)

  • Kim, Yun-Hee;Han, Jae-Kyung;Kim, Yun-Hee
    • The Journal of Pediatrics of Korean Medicine
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    • v.22 no.1
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    • pp.69-93
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    • 2008
  • Objectives The purpose of this study is to investigate the effect of KKHS on atopic dermatitis in an in-vivo experiment using an NC/Nga atopic dermatitis mouse, which has histological and clinical similarities to this condition in humans. Methods To investigate the effect of KKHS on atopic dermatitis (AD), we evaluated atopic dermatitis-like skin lesions by clinical skin index and analyzed immunological parameters in peripheral blood mononuclear cells(PBMCs), splenocytes, draining lymph node(DLN) and performed skin histology in ears and dorsal skin of atopic dermatitis of NC/Nga mouse in vivo. Results In vivo, clinical skin severity score was significantly lower in the KKHS group than in the control group. IgE, IL-6, TNF-${\alpha}$, IgM, IgG2a and IgG2b levels in serum decreased remarkably in the KKHS group than in the control group, and the level of IFN-${\gamma}$ production which is secreted from Th1 cell was increased by KKHS. After this experiment we analyzed immunological cells ($CD3^+$, $CD19^+$, $CD4^+$, $CD8^+$, $CD3^+CD69^+$, $CD4^+CD25^+$ and $CD49b^+$) by flow cytometry. It results that the total absolute number of $CD3^+$, $CD19^+$, $CD4^+$ and $CD8^+$ cells were recovered as much as normal state, and the level of $CD3^+CD69^+$ in isolated DLN and PBMCs were significantly decreased, and total absolute number of $Gr-1^+$, $CD11b^+$ and $CD3^+$ in dorsal skin of NC/Nga mouse were decreased by KKHS. We analyzed ear, DLN, and neck-back skin after biopsy and dyeing by hematoxyline/eosin(H&E), toluidine staining (mast cells marker). KKHS were very effective to the histological symptoms which are in dermal and epidermal thickening, hyperkeratosis and inflammatory cell infiltration. Ear thickness was significantly decreased compared with the control group and the size of inflammatory lymphocytes cells (ILC) and plasma cells (PC) in DLN were also decreased. Conclusions KKHS on atopic dermatitis in an in-vivo experiment using an NC/Nga atopic dermatitis mouse was very effectiveness to the atopy dermatitis treatment.

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Ginsenoside Rg3 ameliorates myocardial glucose metabolism and insulin resistance via activating the AMPK signaling pathway

  • Ni, Jingyu;Liu, Zhihao;Jiang, Miaomiao;Li, Lan;Deng, Jie;Wang, Xiaodan;Su, Jing;Zhu, Yan;He, Feng;Mao, Jingyuan;Gao, Xiumei;Fan, Guanwei
    • Journal of Ginseng Research
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    • v.46 no.2
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    • pp.235-247
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    • 2022
  • Background: Ginsenoside Rg3 is one of the main active ingredients in ginseng. Here, we aimed to confirm its protective effect on the heart function in transverse aortic coarctation (TAC)-induced heart failure mice and explore the potential molecular mechanisms involved. Methods: The effects of ginsenoside Rg3 on heart and mitochondrial function were investigated by treating TAC-induced heart failure in mice. The mechanism of ginsenoside Rg3 for improving heart and mitochondrial function in mice with heart failure was predicted through integrative analysis of the proteome and plasma metabolome. Glucose uptake and myocardial insulin sensitivity were evaluated using micro-positron emission tomography. The effect of ginsenoside Rg3 on myocardial insulin sensitivity was clarified by combining in vivo animal experiments and in vitro cell experiments. Results: Treatment of TAC-induced mouse models with ginsenoside Rg3 significantly improved heart function and protected mitochondrial structure and function. Fusion of metabolomics, proteomics, and targeted metabolomics data showed that Rg3 regulated the glycolysis process, and Rg3 not only regulated glucose uptake but also improve myocardial insulin resistance. The molecular mechanism of ginsenoside Rg3 regulation of glucose metabolism was determined by exploring the interaction pathways of AMPK, insulin resistance, and glucose metabolism. The effect of ginsenoside Rg3 on the promotion of glucose uptake in IR-H9c2 cells by AMPK activation was dependent on the insulin signaling pathway. Conclusions: Ginsenoside Rg3 modulates glucose metabolism and significantly ameliorates insulin resistance through activation of the AMPK pathway.

Pharmacokinetic Profiles of Isoniazid and Rifampicin in Korean Tuberculosis Patients (한국인 결핵환자에서 Isoniazid와 Rifampicin의 약동학)

  • Ahn, Seok-Jin;Park, Sang-Joon;Kang, Kyeong-Woo;Suh, Gee-Young;Chung, Man-Pyo;Kim, Ho-Joong;Kwon, O-Jung;Rhee, Chong-H.;Cha, Hee-Soo;Kim, Myoung-Min;Choi, Kyung-Eob
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.4
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    • pp.442-450
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    • 1999
  • Background : Isoniazid(INH) and rifampicin(RFP) are the most effective anti-tuberculosis drugs which make the short-course chemotherapy possible. Although prescribed dosages of INH and RFP in Korea are different from those recommended by American Thoracic Society, there has been few study about pharmacokinetic profiles of INH and RFP in Korean patients who receive INH, RFP, ethambutol(EMB) and pyrazinamide(PZA) simultaneously. Methods : Among the patients with active tuberculosis from Dec. 1997 to July 1998, we selected 17 patients. After an overnight fast, patients were given INH 300mg, RFP 450mg, EMB 800mg and PZA 1500mg daily. Blood samples for the measurement of plasma INH(n=15) and RFP(n=17) level were drawn each at 0, 0.5, 1, 1.5, 2, 4, 6, 8 and 12hrs, and urine was also collected. INH and RFP level in the plasma and the urine were measured by high-performance liquid chromatography(HPLC). Pharmacokinetic parameters such as peak serum concentration(Cmax), time to reach to peak serum concentration(Tmax), half-life, elimination rate constant(Ke), total body clearance(CLtot), nonrenal clearance(CLnr), and renal clearance(CLr) were calculated. Results : 1) Pharmacokinetic parameters of INH were as follows: Cmax; $7.63{\pm}3.20{\mu}g/ml$, Tmax; $0.73{\pm}0.22hr$, half-life; $2.12{\pm}0.84hrs$, Ke; $0.83{\pm}0.15hrs^{-1}$, CLtot; $17.54{\pm}8.89L/hr$, CLnr; $14.74{\pm}8.35L/hr$, CLr; $2.79{\pm}1.31L/hr$. 2) Pharmacokinetic parameters of RFP were as follows: Cmax; $8.93{\pm}3.98{\mu}g/ml$, Tmax; $1.76{\pm}1.13hrs$, half-life; $2.27{\pm}0.54hrs$, Ke; $0.32{\pm}0.08hrs^{-1}$, CLtot; $14.63{\pm}6.60L/hr$, CLr; $1.04{\pm}0.55L/hr$, CLnr; $13.59{\pm}6.21L/hr$. 3) While the correlation between body weight and Cmax of INH was not statistically significant (r=-0.514, p value>0.05), Cmax of RFP was significantly affected by body weight of the patients(r=-0.662, p value<0.01). Conclusion : In Korean patients with tuberculosis, 300mg of INH will be sufficient to reach the ideal peak blood level even in the patients over 50kg of body weight However, 450mg of RFP will not be the adequate dose in the patients who weigh over 50~60kg.

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Clinicopathological Effects of Waterpepper (Persicaria hydropiper) on Ruminants (여뀌섭취가 반추수에 비치는 임상병리학적 영향)

  • Cho Myoung-Rae;Han Hong-Ryul
    • Journal of Veterinary Clinics
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    • v.6 no.2
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    • pp.227-259
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    • 1989
  • Waterpepper is a weed which grows on damp soil. especially near swamps, and in shallow water of ponds and ditches. It Is widespread throughout the country In abundant colonies. In the present experiments, possible toxic effects of waterpepper were investigated in ruminants. Pour cows were fed waterpepper ad libitum or by force in the from of green forage, hay and/or powder, 8 goats were administered in the form of methanol extract, and 4 goats, crude juice, into the lumen. Clinical signs were examined as well as urinalysis, hematology, serum chemical analysis, pH/blood gas analysis and chclinesterase activities following administration of waterpepper. Six goats which were administered the methanol extract or crude juice were sacrificed for pathological examinations., In addition to the clini copathological examinations, the chemical constituents of waterpepper were qualitively analyzed from the methanol extract and the Effects of the waterpepper crude juice were examined on the motility of rabbit duodenum and uterus. It is revealed that waterpepper contains steroids, terpenoids, flavonoids, tannin and essential oils in the methanol extract and nitrates in the crude juice. The crude juice of waterpepper relaxed the rabbit uterine and duodenal smooth muscles. The constraction of duodenum by acetylcholine or BaCl$_2$ were partially inhibited by pretreatment of the crude juice. However, the relaxation of duodenum by the crude juice was not blocked by the pretreatments of phenoxybenzamlne, propranolol, cocaine, reserpine and tetrodotoxin. The constituents of waterpepper to evoke elaxation of duodenal smooth muscle were stable to heat. The cows administered waterpepper showed common clinical symptoms such as acrid expression, restlessness, dullness, inappetence, anorexia, severe diarrhea, mild bloat and left displacement of abomasum, while bloody feces was shown in a cow. The goats administered the mothanol extract showed common clinical signs such as acrid expression, restlessness, dullness, inappetence and soft feces, while bloody feces was shown in a goat, A goat adminstered the crude juice showde bloody feces and diarrhea. Respiratory rates and heart beats were increased along with diarrhea in the experimental cows. The erythrocyte counts and MCHC were decreased whereas PCV, MCV and neutrophils were increased in the cows administered waterpepper. In goats administered methanol extract, there were decreases in erythrocytes, PCV and hemoglobin content, and an increase in MCHC. The goats ingester with the crude juice showed negligible changes in hematologic values compared with control group which was administered the same amount of water instead of the crude juice. The contents of serum calcium, Inorganic phosphorus, magnesium, Iron, glucose, cholesterol, total protein, triglycerides and phospholipids were tended to decrease in cows. In goats serum iron, glucose, triglycerides, cholesterol, BUN and phospholipids content were decreased while the content of sodium and chloride were increased after administration of the methamol extract The goats ingested with the crude juice did not show significant changes in serum chemical analysis. Even though there were some pathological findings such as hyperemia in the small intestines and kidneys and swelling of liver parenchymal cells, the values of serum AST, ALT, LDH, alkaline phosphatase, total bilirubin and creatinine did not change significantly. While proteins, hemoglobin and blood were detected in the urine of cows, urine pH, ketone bodies, glucose, bilirubin and urobilinogen content were normal or undetected. There were no significant changes in pH/bolld gas analysis data of cows and cholinesterase activities of plasma and erythrocytes of cows and goats ingested with waterpepper or the methanol extract. It is concluded that waterpepper irritates the gatrointestinal system, causes abdominal pain, relaxes the gastrointestinal smooth muscle and dilatates blood vessels supplied to the system. The irritation and relaxation may lead to abnormal fermentation, maldigestion and malabsorption of nutrients and result in diarrhea, body feces, mild bloat and left displacement of abomasum.

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DRAG EFFECT OF KOMPSAT-1 DURING STRONG SOLAR AND GEOMAGNETIC ACTIVITY (강한 태양 및 지자기 활동 기간 중에 아리랑 위성 1호(KOMPSAT-1)의 궤도 변화)

  • Park, J.;Moon, Y.J.;Kim, K.H.;Cho, K.S.;Kim, H.D.;Kim, Y.H.;Park, Y.D.;Yi, Y.
    • Journal of Astronomy and Space Sciences
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    • v.24 no.2
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    • pp.125-134
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    • 2007
  • In this paper, we analyze the orbital variation of the Korea Multi-Purpose SATellite-1(KOMPSAT-1) in a strong space environment due to satellite drag by solar and geomagnetic activities. The satellite drag usually occurs slowly, but becomes serious satellite drag when the space environment suddenly changes via strong solar activity like a big flare eruption or coronal mass ejections(CMEs). Especially, KOMPSAT-1 as a low earth orbit satellite has a distinct increase of the drag acceleration by the variations of atmospheric friction. We consider factors of solar activity to have serious effects on the satellite drag from two points of view. One is an effect of high energy radiation when the flare occurs in the Sun. This radiation heats and expands the upper atmosphere of the Earth as the number of neutral particles is suddenly increased. The other is an effect of Joule and precipitating particle heating caused by current of plasma and precipitation of particles during geomagnetic storms by CMEs. It also affects the density of neutral particles by heating the upper atmo-sphere. We investigate the satellite drag acceleration associated with the two factors for five events selected based on solar and geomagnetic data from 2001 to 2002. The major results can be summarized as follows. First, the drag acceleration started to increase with solar EUV radiation with the best cross-correlation (r = 0.92) for 1 day delayed F10.7. Second, the drag acceleration and Dst index have similar patterns when the geomagnetic storm is dominant and the drag acceleration abruptly increases during the strong geomagnetic storm. Third, the background variation of the drag accelerations is governed by the solar radiation, while their short term (less than a day) variations is governed by geomagnetic storms.

Effect of buchu (Allium tuberosum) on lipid peroxidation and antioxidative defense system in streptozotocin-induced diabetic rats (부추가 Streptozotocin 유발 당뇨쥐의 지질과산화와 항산화방어체계에 미치는 영향)

  • 송영선;정현실;노경희;조혜연;박지영;최춘연;권태완
    • Journal of Life Science
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    • v.13 no.3
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    • pp.333-342
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    • 2003
  • The pathogenic effort of high glucose, possibly in concert with fatty acids, is mediated to vascular complications of diabetes via increased production of reactive oxygen species(ROS), reactive nitrogen species(RNS), and subsequent oxidative stress. This study was carried out to investigate the suppressive effect of buchu(Allium tuberosum) on oxidative stress in streptozotocin(STZ)-induced diabetes in Sprague Dawley male rats. The effect of buchu supplementation (10%) on lipid peroxidation, and antioxidative defense system in blood and liver was compared among normal rats fed basal diet(normal) and diabetic rats fed basal diet(DM-control) or 10% buchu-supplemented diet(DM-buchu). Diabetes was experimentally induced by the femoral muscle injection of 50 mg STZ per kg of body weight. Animals were sacrificed after 4 wks of experimental diets feeding. The induction of diabetes by STZ elevated the level of lipid peroxidation represented by thiobarbituric acid-reactive substances(TBARS) and conjugated dienes in plasma, LDL, liver, and erythrocytes. 10% buchu-supplemented diet significantly reduced the levels of conjugated dienes in erythrocytes(p<0.05) and lowered TBARS in liver and LDL to the levels of control. Induction of diabetes by STZ elevated Mn-superoxide dismutase(Mn-SOD) activity and lowered activities of glutathionine reductase(GSH-red) and glutathionine peroxidase(GSH-px). Catalase activity was not affected by the induction of diabetes by STZ. However, buchu supplementation to diabetic rats significantly elevated catalase activity(p<0.05) and slightly elevated GSH-px and GSH-red activities in liver. GSH levels of blood and liver were lowered or not changed by induction of diabetes by STZ, respectively, while buchu supplementation to diabetic rats significantly elevated hepatic GSH level (p<0.05). In conclusion, it can be concluded that buchu might be a food source to attenuate oxidative stress in diabetic patients by inhibiting lipid peroxidation, by increasing hepatic GSH level, and by inducing anti-oxidative enzyme systems.

Selective determination of mercury (II) ion in aqueous solution by chemiluminescence method (화학발광법에 의한 수용액 중의 선택적 수은(II) 이온 정량)

  • Kim, Kyung-Min;Jang, Taek-Gyun;Kim, Young-Ho;Oh, Sang-Huyb;Lee, Sang-Hak
    • Analytical Science and Technology
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    • v.24 no.4
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    • pp.243-248
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    • 2011
  • A selective determination method of mercury (II) ion in aqueous solution by luminol-based chemiluminescence system (luminol CL system) has been developed. Determination of metal ions such as copper (II), iron (III), chromium (III) ion in solution by the luminol CL system using its catalytic role in the reaction of luminol and hydrogen peroxide has been reported by several groups. In this study, the catalytic activity of mercury (II) ion in the reaction of luminol and hydrogen peroxide was observed by the enhanced CL intensity of the luminol CL system. Based on this phenomenon, experimental conditions of the luminol CL system were investigated and optimized to determine mercury (II) ion in aqueous solution. While mercury (II) ion in mixed sample solution containing mercury (I) and (II) ions highly enhanced the CL intensity of the luminol CL system, the mercury (I) ion could not enhanced the CL intensity. Thus selective determination of the mercury (II) ions in a mixture containing mercury (I) and (II) ions could be achieved. Each concentration of mercury (I) and (II) ions in aqueous solution can be obtained from the results of the CL method that give the concentration of only mercury (II) ion and the inductively coupled plasma (ICP) method that give the total concentration of mercury ions. On the optimized conditions, the calibration curve of mercury (II) ion was linear over the range from $1.25{\times}10^{-5}$ to $2.50{\times}10^{-3}M$ with correlation coefficient of 0.991. The detection limit of mercury (II) ion in aqueous solution was calculated to be $1.25{\times}10^{-7}M$.

Effects of Level and Degradability of Dietary Protein on Ruminal Fermentation and Concentrations of Soluble Non-ammonia Nitrogen in Ruminal and Omasal Digesta of Hanwoo Steers

  • Oh, Young-Kyoon;Kim, Jeong-Hoon;Kim, Kyoung-Hoon;Choi, Chang-Won;Kang, Su-Won;Nam, In-Sik;Kim, Do-Hyung;Song, Man-Kang;Kim, Chang-Won;Park, Keun-Kyu
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.3
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    • pp.392-403
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    • 2008
  • Four ruminally fistulated Hanwoo steers were used to determine the effects of level and degradability of dietary protein on ruminal fermentation, blood metabolites and concentration of soluble non-ammonia nitrogen (SNAN) in ruminal (RD) and omasal digesta (OD). Experiments were conducted in a $4{\times}4$ Latin square design with a $2{\times}2$ factorial arrangement of treatments. Factors were protein supplements with two ruminal crude protein (CP) degradabilities, corn gluten meal (CGM) that was low in degradability (rumen-degraded protein (RDP), 23.4% CP) or soybean meal (SBM) that was high in degradability (RDP, 62.1% CP), and two feeding levels of CP (12.2 or 15.9% dry matter). Ruminal fermentation rates and plasma metabolite concentrations were determined from the RD collected at 2-h intervals and from the blood taken by jugular puncture, respectively. The SNAN fractions (free amino acid, peptide and soluble protein) in RD and OD collected at 2-h intervals were assessed by ninhydrin assay. Mean ruminal ammonia concentrations were 40.5, 74.8, 103.4 and 127.0 mg/L for low CGM, high CGM, low SBM and high SBM, respectively, with statistically significant differences (p<0.01 for CP level and p<0.001 for CP degradability). Blood urea nitrogen concentrations were increased by high CP level (p<0.001) but unaffected by CP degradability. There was a significant (p<0.05) interaction between level and degradability of CP on blood albumin concentrations. Albumin was decreased to a greater extent by increasing degradability of low CP diets (0.26 g/dl) compared with high CP diets (0.02 g/dl). Concentrations of each SNAN fraction in RD (p<0.01) and OD (p<0.05) for high CP diets were higher than those for low CP diets, except for peptides but concentrations of the sum of peptide and free amino acid in RD and OD were significantly higher (p<0.05) for high CP diets than for low CP diets. Soybean meal diets increased free amino acid and peptide concentrations in both RD (p<0.01) and OD (p<0.05) compared to CGM diets. High level and greater degradability of CP increased (p<0.001) mean concentrations of total SNAN in RD and OD. These results suggest that RDP contents, increased by higher level and degradability of dietary protein, may increase release of free amino acids, peptides and soluble proteins in the rumen and omasum from ruminal degradation and solubilization of dietary proteins. Because SNAN in OD indicates the terminal product of ruminal metabolism, increasing CP level and degradability appears to increase the amount of intestine-available nitrogen in the liquid phase.