• Title/Summary/Keyword: Human plasma

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Quantitative Analysis of Lovastatin in Human Plasma and urine by Reversed-Phase High-Performance Liquid Chromatography (역상 고속액체크로마토그라프법을 이용한 혈장 및 뇨 중 로바스타틴의 정량)

  • Choi, Hye-Jin;Kim, Myoung-Min;Choi, Kyung-Eob
    • YAKHAK HOEJI
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    • v.42 no.5
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    • pp.473-479
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    • 1998
  • Lovastatin (LOVA), a fungal metabolite isolated from cultures of Aspergillus terreus, is a competitive HMG-CoA reductase inhibitor used for the treatment of primary hyper cholesterolemia, and has also been shown to suppress growth in a variety of non-glioma tumor cell lines. A sensitive reversed-phase high-perfonnance liquid chromatographic method with ultraviolet (UV) absorbance detection has been developed to quantitate LOVA in human plasma and urine samples using liquid-liquid extraction procedure. Baseline separation of LOVA and internal standard, simvastatin was achieved on a Novapak $C_{18}$ analytical column with a mobile phase containing 0.025M $NaH_2PO_4$: CAN (35:65, v/v%), adjusted pH to 4.5. The flow rate was set at 1.5ml/min, and the column effluent was monitored by a UV detection at 238nm. The limit of quantification was determined to be 0.5${\mu}$g/ml while extraction efficiency of LOVA ranged from 73.4-82.9% at LOVA concentrations of 0.5 to 10${\mu}$g/ml. Good linearity with correlation coefficients greater than 0.999 was obtained in the range of LOVA concentrations from 0.5 to 10${\mu}$g/ml. The accuracy and the precision were proven excellent with relative standard deviation (RSD, %) and relative error (RE, %) of less than 4.2 and 4.0, respectively. Intraday precision, evaluated at five LOVA concentrations (0.5, 1, 2, 5, 10${\mu}$g/ml) and expressed as RSD ranged from 0-1.82% while the interday precision at the same concentrations ranged from 0.7-10.5%. The analytical method described was then successfully employed for the determination of LOVA concentrations in plasma samples obtained during a phase II clinical trial using high doses of LOVA (30-40mg/kg/day). This method could be further utilized for the ongoing pharmacolkinetic studies and therapeutic drug monitoring of the high-dose LOVA therapy in adenocarcinoma patients.

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Physicochemical Properties, Stabilities and Pharmacokinetics of Cephalosporin 3'-Quinolone Dithiocarbamate (세팔로스포린 3'-퀴놀론의 물리화학적 성질, 안정성 및 체내약물동태)

  • 나성범;공재양;김완주;지웅길
    • YAKHAK HOEJI
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    • v.37 no.6
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    • pp.638-646
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    • 1993
  • A cepfialosporin with an aminothiazoiylmethoxyimino-type side chain at the 7 position and bicyclic quinolone dithicarbamate at the 3' position was synthesized. It has broad and potent antivacterial activity in vitro. The antibacterial spectrum reflects contributions of both the cephalosporin moiety and the quinolone moiety. Thus, this compound was named DACD implying a dualaction cephalosporin derivative. In this paper, the physicochemical proper-ties (lipid-water partition, pKa), stability and pharmacokinetics of DACD were determined and compared with cefotaxime 3'-norfloxacin dithiocarbamate (CENO). Stability tests were studied in pH 1.20, 6.80 and 8.00 buffers and in the presence of AB type human plasma, rat liver homogenate and its .betha.-lactamase. The pharmacokinetic parameters of DACD were evaluated in mice after a single intravenous dose of 40 mg/kg. The results are as follows. The lipid-water partition coefficient of DACD was higher than that of CENO. The calculated pKa values of CENO and DACD, were 6.82$\pm$0.03, 7.53$\pm$0.21, respectively. In the hydrolysis test, half-lives (t$^{1/2}$) of CENO and DACD was 66.0 hr and 80.0 hr in pH 6.80 buffer, 190 hr and 91.4 hr in pH 8.00 buffer. CENO and DACD were rapidly hydrolyzed in human plasma and in rat liver hornogenate. Half-lives (t$_{1/2}$ of CENO and DACD were 1.29 hr and 1.15 hr in hyman plasma, 0.62 hr and 0.71 hr rat liver homogenate. In $\beta$-lactamase stability test, CENO and DACD were very stable to the .betha.-lactamases obtained from three different strains. Half-life (t$_{1/2}$) and areas under the curve (AUC) in mice were 2.33 hr and 15.97 (mg.h/1), respectively.

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Removal and Inactivation of Viruses during Manufacture of a High Purity Antihemophilic Factor VII Concentration from Human Plasma

  • Kim, In-Seop;Choi, Yong-Woon;Lee, Sung-Rae;Woo, Hang-Sang;Lee, Soung-Min
    • Journal of Microbiology and Biotechnology
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    • v.11 no.3
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    • pp.497-503
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    • 2001
  • The purpose of this study was to examine the efficacy and mechanism of the cryo-precipitation, solvent/detergent (S/D) treatment, monoclonal anti-FVIIIc antibody (mAb) column chromatography, Q-Sepharose column chromatography, and lyophilization involved in the manufacture of antithemophilic factor VII(GreenMono) from human plasma, in the removal and/or inactivation of blood-borne viruses. A variety of experimental model viruses for human pathogenic viruses, including the bovine viral diarrhoea virus (BVDV), bovine herpes virus (BHV), murine encephalomyocarditis virus (EMCV), and porcine parvovirus (PPV), were all selected for this study. BHV and EMCV were effectively partitioned from a factor VII during the cryo-precipitation with a log reduction factor of 2.83 and 3.24, respectively. S/D treatment using the organic solvent, tri(n-butyl) phosphate (TNBP), and the detergent, Triton X-100, was a robust and effective step in inactivating enveloped viruses. The titers of BHV and BVDV were reduced from the initial titer of 8.85 and $7.89{log_10} {TCID_50}$, respectively, reaching undetectable levels within 1 min of the S/D treatment. The mAb chromatography was the most effective step for removing nonenveloped viruses, EMCV and PPV, with the log reduction factors of 4.86 and 3.72, respectively. Q-Sepharose chromatography showed a significant efficacy for partitioning BHV, BVDV, EMCV, and PPV with the log reduction the log reduction factors of 2.32, 2.49, 2.60, and 1.33 respectively. Lyophilization was an effective step in inactivating g nonenveloped viruses rather than enveloped viruses, where the log reduction factors of BHV, BVDV, DMCV, and PPV were 1.41, 1.79, 4.76, and 2.05, respectively. The cumulative log reduction factors of BHV, BVDV, EMCV, and PPV were ${\geqq}$11.12, ${\geqq}$7.88, 15.46, and 7.10, respectively. These results indicate that the production process for GreenMono has a sufficient virus-reducing capacity to achieve a high margin of the virus safety.

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Plasma Medicine: How can Nonthermal Atmospheric Plasma be Applied to Medicine? (플라즈마 메디신: 저온 상압 플라즈마는 어떻게 의학분야에 적용될 수 있는가?)

  • Park, Sang Rye;Hong, Jin Woo;Lee, Hae June;Kim, Gyoo Cheon
    • Journal of Life Science
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    • v.23 no.6
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    • pp.838-846
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    • 2013
  • As a forth state of material, plasma is ionized gas, which generates characteristically various reactive species. After late of $20^{th}$ century, plasma has been widely used in industry. After nonthermal atmospheric plasma was developed, it has been applied to biomedical fields. Nonthermal atmospheric plasma does not give thermal damages to human tissues, and it shows the high efficiency in cancer treatment, sterilization, tooth bleaching, coagulation, and wound healing. Because the application of plasma to biomedicine has been expanded through interdisciplinary studies, its value of high medical technology is increasing now. Since nonthermal atmospheric plasma was first applied to the mammalian cells and microorganisms, many valuable studies has been performed for about last 10 years, so that now the new research area called 'plasma medicine' has been formed. This article introduces the recent data resulted from plasma medicine and helps to understand the plasma medicine.

Effects of Plasma Lipoproteins on Expression of Vasular Cell Adhesion Molecule- in Human Microvasuclar Endothelial Cells (혈관내피세포에서 Vascular Cell Adhesion Molecule-1 발현에 대한 혈장 지단백의 효과)

  • 박성희
    • Journal of Nutrition and Health
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    • v.31 no.8
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    • pp.1235-1243
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    • 1998
  • Although an elevated plasma level of high density lipoprotein (HDL) is known as a protective component against the development of atherosclerosis and ensuing coronary heart diseases, the related mechanisms are still not established . It has been clearly demonstrated in the early stages of atherogenesis that adhesion of monocytes and lymphocytes to the vascular endothelium is enhanced via adhesion molecules, and that monocytes and macrophages accumulate in the subendothelial space. The present study has investigated whether isolated plasma HDL plays a role in protection against atherogenesis by inhibiting the expression of vascular cell adhesioin molecule-1(VCAM-1) on the endothelial cells. Effects of plasma native low density lipoprotein (LDL) and ac ethylated LDL(AcLDL) on VCAM-1 expression were also examined by using an immunocytochemical technique. While plasma HDL did not alter the basal expression of VCAM-1 , lipopolysaccharide(LPS) induction of this adhesion modlecule was markedly inhibited at a phyaiological concentration of HDL. In contrast, 30$\mu\textrm{g}$ protein/ml AcLDL increased sifnificantly both basal VCAM-1 expression and its LPD induction , suggesting that this modified LDL enhances leukocyte adhesiion to endothelial cells. Unlike AcLDL , plasma native LDL inhibited significantly VCAM-1 expression. This indicates that LDL did not undergo oxidative modificantion while incubated with endothelial cells. These results suggest that plasam HDL may inhibit atherogenesis by reducing the expression of adhesion molecules, which is a protective mechanism independent of tis reverse cholesterol transport function . Modified LDL is a potent iducer for adhesion molecules in vascular endothelical cells and could play a role in the pathogenesis of atherosclerosis by adhering to blood cells.

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The Associations between Plasma Concentrations of Total Radical-Trapping Antioxidant Potential(TRAP), Antioxidant Vitamins and DNA Damage in Human Lymphocytes (혈장 총 율기 포집 능력(TRAP) 수준 및 항산화 비타민 영양상태와 인체 임파구 DNA 손상정도와의 상호관련성 연구)

  • 강명희
    • Journal of Nutrition and Health
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    • v.34 no.4
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    • pp.401-408
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    • 2001
  • The spontaneous frequency of genetic damage and the possible relationship of this damage to total radical-trapping antioxidant potential(TRAP) and antioxidant vitamins, including plasma levels of $\alpha$-carotene, $\beta$-carotene, cryptoxanthin, retinol, $\alpha$-tocopherol and ${\gamma}$-tocopherol in humans were investigated in 57 subjects using two indices of genetic damage, SCE & HFC frequency. The mean of SCE and HFC frequencies were weakly correlated with plasma TRAP(r=-0.305, p<0.1 for SCEs: r=-0.297, p<0.1 for HFCs, respectively), but those were strongly negatively correlated with plasma $\beta$-carotence(r=-0.385, p<0.01 for SCEs : r=-0.392, p<0.01 for HFCs) and cryptoxanthin(r=-0.312, p<0.05 for SCEs : r=0.335, p<0.05 for HFCs, respectively) levels in the subjects. However, those DNA damage markers including SCE and HFC did not correlate with either plasma $\alpha$-carotene, $\alpha$-tocopherol or retinol concentrations. The mean of SCE and HFC frequencies were positively correlated with plasma ${\gamma}$-tocopherol level(r=0.421, p<0.01 for SCEs : r=0.399, p<0.01 for HFCs, respectively). These findings indicate that increased cytogenetic DNA changes, as determined by SCE and HFC frequencies are possibly associated with generation of free radicals in lymphocytes and decreased plasma antioxidant vitamin($\beta$-carotene and cryptoxanthin) status in the subjects. (Korean J Nutrition 34(4) : 401~08, 2001)

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Dentinal Tubules Occluding Effect Using Nonthermal Atmospheric Plasma

  • Lee, Chang Han;Kim, Young Min;Kim, Gyoo Cheon;Kim, Shin
    • International Journal of Oral Biology
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    • v.43 no.2
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    • pp.83-91
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    • 2018
  • Nonthermal atmospheric plasma has been studied for its many biomedical effects, such as tooth bleaching, wound healing, and coagulation. In this study, the effects of dentinal tubules occlusion were investigated using fluoride-carboxymethyl cellulose (F-CMC) gel, nano-sized hydroxyapatite (n-HA), and nonthermal atmospheric plasma. Human dentin specimens were divided to 5 groups (group C, HA, HAF, HAP, and HAFP). Group HA was treated with n-HA, group HAF was treated with n-HA after a F-CMC gel application, group HAP was treated with n-HA after a plasma treatment and group HAFP was treated with n-HA after a plasma and F-CMC gel treatment. The occlusion of dentinal tubules was investigated using scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDS), which shows Ca/P ratio. In the EDS results, a higher Ca/P ratio was shown in the groups including n-HA than in the control group. The specimens of group HAP and HAFP had a higher Ca/P ratio in retentivity. In the SEM results, there was not a significant difference in the amount of times applied. Therefore, this study suggests F-CMC gel and n-HA treatment using nonthermal atmospheric plasma will be a new treatment method for decreasing hypersensitivity.

A Study on Polymer Surface Treatment Using Plasma (플라즈마를 이용한 고분자물질의 표면처리에 관한 연구)

  • Park Hee-Lyun;Lim Jong-Min;Seul Soo-Duk;Lee Woo-Nae;Moon Jin-bok
    • Journal of the Korean Society of Safety
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    • v.20 no.1 s.69
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    • pp.94-100
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    • 2005
  • The plasma, ionized gas state, is generally composed as the 4th state in the universe. Generating the plasma artificially has been studied by spending energy and it has been applied so much in human's life. There are several merits to modify the surface of polymer using plasma. Above all, plasma maintains the properties of polymer itself, but changes the properly of polymer surface only. Also, it is the environmentally fraternized because there are no waste processing from organic solvent. Furthermore, it is possible that continuous automated-processing in case of high-pressure plasma. Therefore, we have tried the reforming of surface to rise the adhesive strength between the material of polymer, and have experimented rising the adhesive strength through peel strength by virtue of processing time and using gas, of course, confirmed the change of polymer surface through measuring the contact angle analysis and scanning electron microscopy(SEM).

The interaction of Apolipoprotein A5 gene promoter region T-1131C polymorphism (rs12286037) and lifestyle modification on plasma triglyceride levels in Japanese

  • Yamasaki, Masayuki;Mutombo, Paulin Beya wa Bitadi;Iwamoto, Mamiko;Nogi, Akiko;Hashimoto, Michio;Nabika, Toru;Shiwaku, Kuninori
    • Nutrition Research and Practice
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    • v.9 no.4
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    • pp.379-384
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    • 2015
  • BACKGROUND/OBJECTIVE: Apolipoprotein A5 gene promoter region T-1131C polymorphism (APOA5 T-1131C) is known to be associated with elevated plasma TG levels, although little is known of the influence of the interaction between APOA5 T-1131C and lifestyle modification on TG levels. To investigate this matter, we studied APOA5 T-1131C and plasma TG levels of subjects participating in a three-month lifestyle modification program. SUBJECTS/METHODS: A three-month lifestyle modification program was conducted with 297 participants (Age: $57{\pm}8years$) in Izumo City, Japan, from 2001-2007. Changes in energy balance (the difference between energy intake and energy expenditure) and BMI were used to evaluate the participants' responses to the lifestyle modification. RESULTS: Even after adjusting for confounding factors, plasma TG levels were significantly different at baseline among three genotype subgroups: TT, $126{\pm}68mg/dl$; TC, $134{\pm}74mg/dl$; and CC, $172{\pm}101mg/dl$. Lifestyle modification resulted in significant reductions in plasma TG levels in the TT, TC, and CC genotype subgroups: $-21.9{\pm}61.0mg/dl$, $-20.9{\pm}51.0mg/dl$, and $-42.6{\pm}78.5mg/dl$, respectively, with no significant differences between them. In a stepwise regression analysis, age, APOA5 T-1131C, body mass index (BMI), homeostasis model assessment-insulin resistance (HOMA-IR), and the 18:1/18:0 ratio showed independent association with plasma TG levels at baseline. In a general linear model analysis, APOA5 T-1131C C-allele carriers showed significantly greater TG reduction with decreased energy balance than wild type carriers after adjustment for age, gender, and baseline plasma TG levels. CONCLUSIONS: The genetic effects of APOA5 T-1131C independently affected plasma TG levels. However, lifestyle modification was effective in significantly reducing plasma TG levels despite the APOA5 T-1131C genotype background.