1.Terpenoids and sterols from Ricinus communis and their activities against diabetes.
Shen-Hua LI ; Qing DENG ; Li ZHU ; Chun-Hua LAI ; Heng-Shan WANG ; Qin-Gang TAN
China Journal of Chinese Materia Medica 2014;39(3):448-452
Seven terpenoids and three sterols were isolated from the methanol extracts of the aerial parts of Ricinus communis by chromatography methods and their structures were identified by spectra analysis as ficusic acid( 1), phytol(2), callyspinol(3) , lupeol(4), 30-norlupan-3beta-ol-20-one(5) , lup-20(29)-en-3beta,15alpha-diol(6) , acetylaleuritolic acid( 7), stigmast4-en-3-one(8) , stig-mast-4-en-6beta-ol-3-one(9) , and stigmast4-en-3,6-dione(10). Compounds 1-3 and 5-10 were obtained from this species for the first time and 5 and 6 showed significant inhibitive activity and good selectivity against 11beta-HSD of mouse and human in vitro. [Key words] Ricinus communis; terpenoids; sterols; 11beta-HSD
11-beta-Hydroxysteroid Dehydrogenase Type 1
;
antagonists & inhibitors
;
11-beta-Hydroxysteroid Dehydrogenase Type 2
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antagonists & inhibitors
;
Animals
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Diabetes Mellitus
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drug therapy
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enzymology
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Humans
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Hypoglycemic Agents
;
pharmacology
;
therapeutic use
;
Inhibitory Concentration 50
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Mice
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Ricinus
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chemistry
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Sterols
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pharmacology
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therapeutic use
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Terpenes
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pharmacology
;
therapeutic use
2.Determination of plasma concentration of five phenolic acid by LC-MS/MS and study of pharmacokinetics in rats after Mailuoning injection.
Ting WU ; Jun ZHANG ; Heng-Shan TAN ; Wen-Zheng JU ; Xiang-Yang XU
China Journal of Chinese Materia Medica 2014;39(10):1928-1932
To establish a LC-MS/MS method for quantification of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid in rats plasma and study its pharmacokinetics after administration of Mailuoning injection at a single dose to rats. Plasma samples were acidified with hydrochloric acid and extracted with ethyl acetate. The analytes were determined by LC-MS-MS using a ZOBAX SB C18 column with a mobile phase of methanol-water (containing 2 mmol x L(-1) ammonium acetic) (60:40)at a flow rate of 0.5 mL x min(-1) and detected using ESI with negative ionization mode. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 353.1/191.0 [M-H]- for chlorogenic acid, m/z 178.9/134.9 [M-H]- for caffeic acid, m/z 515.2/353.0 [M-H]-for 3,4-DCQA, m/z 193.0/133.9 [M-H]-for ferulic acid, m/z 146.9/102.9 [M-H]- for cinnamic acid and m/z 246.0/125.8 [M-H]- for tinidazole (IS). After administration of Mailuoning injection at a single dose to eight Sprague-Dawley rats, the concentrations of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid in plasma were determined by LC-MS/MS method. The main pharmacokinetics parameters of measured data were caluculated by using DASver 1.0 software. The linear concentration ranges of the calibration curves for chlorogenic acid, caffeic acid, 3,4-DCQA and cinnamic acid were 2.006-1,027 microg x L(-1) (r = 0.999 6), 1.953-1,000 microg x L(-1) (r = 0.999 7), 28.51-1.459 x 10(4) microg x L(-1) (r = 0.998 9), 1.836-940.0, g x L(-1) (r = 0.997 7) and 4.780-2,447 microg x L(-1) (r = 0.998 6) respectively. The inner and inter-days relative standard deviations were both less than 5.0%, indicating legitimate precise and accuracy to the requirement of biological sample analysis. For chlorogenic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (49.78 +/- 12.81) min, (123.55 +/- 14.82) mg x min x L(-1) and (0.004 3 +/- 0.000 5) L x min(-1), respectively. For caffeic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (36.65 +/- 10.59) min, (91.67 +/- 11.77) mg x min L(-1) and (0.005 7 +/- 0.000 7) L x min(-1), respectively. For 3,4-DCQA, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (50.08 +/- 13.78) min, (278.34 +/- 31.82) mg x min x L-1 and (0.001 6 +/- 0.000 2) L x min(-1), respectively. For ferulic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (51.39 +/- 15.52) min, (34.72 +/- 4.67) mg x min x L(-1) and (0.000 4 +/- 0.0001) L x min(-1), respectively. For cinnamic acid, the pharmacokinetic parameter t1/2, AUCo-t, and CL were (74.42 +/- 18.32) min, (34.63 +/- 4.82) mg x min x L(-1) and (0.007 7 +/- 0.001 1) L x min-', respectively. The assay method is proved to be sensitive, accurate and convenient. It can be applied to the pharmacokinetic study of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid.
Animals
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Chromatography, Liquid
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methods
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Drugs, Chinese Herbal
;
administration & dosage
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pharmacokinetics
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Female
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Hydroxybenzoates
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blood
;
pharmacokinetics
;
Male
;
Rats
;
Rats, Sprague-Dawley
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Tandem Mass Spectrometry
;
methods
3.Study of change in activity of hepatic drug metabolism enzymes in rat model of chronic unpredictable mild stress.
Yu-xin ZANG ; Bing-ting SUN ; Wen-zhu ZHAO ; Na RONG ; Guo-liang DAI ; Wen-zheng JU ; Heng-shan TAN
Acta Pharmaceutica Sinica 2015;50(3):319-325
This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.
Animals
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Chlorzoxazone
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metabolism
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Chromatography, Liquid
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Cytochrome P-450 Enzyme System
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metabolism
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Depression
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Dextromethorphan
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metabolism
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Liver
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enzymology
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Midazolam
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metabolism
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Omeprazole
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metabolism
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Rats
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Stress, Physiological
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Tandem Mass Spectrometry
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Theophylline
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metabolism
;
Tolbutamide
;
metabolism
4.Effects of needling acupoints at different nerve segments on oxytocin neurons in rat's hypothalamic paraventricular nucleus and intragastric pressure
Chun-Yan YONG ; Shu CHEN ; Heng CHEN ; Xiao CHU ; Chao ZHANG ; Cheng TAN ; Lan YE ; Jiang-Shan LI
Journal of Acupuncture and Tuina Science 2019;17(5):297-304
Objective:To compare and explore the effects of needling acupoints at different nerve segmentson the oxytocin (OT) neurons in the paraventricular nucleus of hypothalamus (PVN) and the intragastric pressure, and discuss the possible mechanisms. Methods: Thirty-two healthy adult Sprague-Dawley (SD) rats were numbered and divided into 4 groups according to the random number table, a Zusanli (ST 36) group, a Neiguan (PC 6) group, a Weishu (BL 21) group and a control group, with 8 rats in each group. Except the control group, rats in the other three groups received acupuncture at the corresponding acupoints. To observe the differences in double-labeled OT neurons and c-fos neurons of the hypothalamic PVN and the intragastric pressure after acupuncture among the three groups of needling acupoints at different nerve segments. Results:Compared with the control group, the numbers of double-labeled cells in the PVN of the Zusanli (ST 36) group and the Neiguan (PC 6) group decreased significantly, while the intragastric pressure increased significantly (allP<0.05), and the inter-group differences were statistically significant (P<0.05). The intragastric pressure in the Weishu (BL 21) group decreased significantly, and the inter-group difference was statistically significant (P<0.05). Compared with the Weishu (BL 21) group, the numbers of OT/c-fos double-labeled cells in PVN of the Zusanli (ST 36) group and the Neiguan (PC 6) group decreased significantly, and the intragastric pressure increased significantly, the inter-group differences were statistically significant (allP<0.01). Conclusion:Acupoints at different nerve segments have different regulation effects on intragastric pressure. The difference may be related to the different nerve conduction pathways by acupoints at different nerve segments in regulating the intragastric pressure. The PVN may be one common integration center for the regulation of gastric function in the three acupoints [Zusanli (ST 36), Neiguan (PC 6) and Weishu (BL 21)] at different nerve segments.
5.Study on significance of single nucleotide polymorphisms in the redox domain of aprimidinic/apurinic endonuclease/redox factor-1 gene in Chinese sporadic colorectal cancer.
Xian-bin TANG ; Jun HOU ; Yun-shan TAN ; Heng-hua ZHOU ; Jia LIU
Chinese Journal of Medical Genetics 2004;21(1):64-67
OBJECTIVETo investigate the relationship between the single nucleotide polymorphisms(SNPs) in the redox domain of aprimidinic/apurinic endonuclease/redox factor-1(APEX) gene and the development of sporadic colorectal cancer.
METHODSOne hundred and fifty cases of sporadic colorectal cancers and 143 peripheral blood samples from healthy population were screened for genetic polymorphisms or mutations in the redox domain by denaturing gradient gel electrophoresis followed by DNA sequencing.
RESULTSThere were two SNPs identified in the redox domain of APEX gene, namely, 453G to T and 1247A to G. The gene frequencies of 453T and 1247G were 1.3% and 5.7%, respectively, in patient group, while 1.05% and 4.55%, respectively, in healthy population. The genotype distribution at the two sites in healthy population was consistent with Hardy-Weinberg equilibrium. There was no difference in gene frequencies at the two sites between cancer patients and healthy population.
CONCLUSIONThe polymorphisms in the redox domain of APEX gene are irrelevant to the development of sporadic colorectal cancer, but their distribution may vary greatly among tribes.
Aged ; Alleles ; Base Sequence ; Binding Sites ; genetics ; China ; Colorectal Neoplasms ; enzymology ; genetics ; pathology ; DNA Mutational Analysis ; DNA, Neoplasm ; chemistry ; genetics ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; genetics ; metabolism ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Oxidation-Reduction ; Point Mutation ; Polymorphism, Single Nucleotide
6.Study on biomarker of Tripterygium wilfordii in treatment of rheumatoid arthritis based on PK/PD.
Shi-jia LIU ; Guo-liang DAI ; Bing-ting SUN ; Chang-yin LI ; Lei WU ; Ma SHI-TANG ; Wen-zheng JU ; Heng-shan TAN ; Hai-yan FU
China Journal of Chinese Materia Medica 2015;40(2):334-338
To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.
Animals
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Arthritis, Rheumatoid
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drug therapy
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immunology
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Biomarkers
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Female
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Interleukin-17
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antagonists & inhibitors
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genetics
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Interleukin-6
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genetics
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Phytotherapy
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Rats
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Rats, Sprague-Dawley
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Tripterygium
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Triterpenes
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pharmacokinetics
;
pharmacology
7.Effect of clopidogrel on plasma protein binding rate of ginsenosides: a liquid chromatography-mass spectrometry-based study.
Shi-Tang MA ; Guo-Liang DAI ; Wen-Zhu ZHAO ; Bing-Ting SUN ; Wen-Zheng JU ; Heng-Shan TAN
Journal of Southern Medical University 2015;35(1):109-112
OBJECTIVETo investigate the effect of clopidogrel on the binding rate of ginsenosides with rat serum proteins (RSA).
METHODSEquilibrium dialysis and liquid chromatography-mass spectrometry were employed to quantify the concentration of ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were determined. A molecular simulation model (consisting of homology modeling and molecular docking interaction) was used to reveal the target protein-compound interactions.
RESULTSThe binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with RSA were (30.16∓2.82)%, (33.42∓4.21)%, and (34.61∓3.42)%, and those of and Rb1 were (50.13∓2.34)%, (51.23∓3.23)%, and (53.11∓3.26)%, respectively. In the presence of clopidogrel, the binding rates of Rg1 decreased to (22.13∓2.72)%, (21.42∓3.22)%, and (25.45∓3.52)%, and those of Rb1 to (40.13∓3.24)%, (41.25∓4.15)%, and (43.11∓3.31)%, receptively. The molecular docking suggested that these compounds competed to bind with RSA.
CONCLUSIONClopidogrel can competitively bind to RSA with ginsenosides to lower the plasma protein binding rates of ginsenosides.
8.Simultaneous determination of baicalin and chlorogenic acid in human plasma by UPLC-MS/MS.
Wen-zheng JU ; Fang LIU ; Ting WU ; Xiao-yan XIA ; Heng-shan TAN ; Xing WANG ; Ning-ning XIONG
Acta Pharmaceutica Sinica 2007;42(10):1074-1077
To develop and validate an ultra performance liquid chromatography tandem mass spectrometric (UPLC-MS/MS) method for the simultaneous quantification of baicalin and chlorogenic acid in human plasma after iv infusion of Yinhuang injection, the analytes were isolated from plasma by protein precipitation with methanol. Then they were chromatographied on an Acquity UPLC BEH C18 column (50 mm x 2.1 mm ID, 1.7 microm) at 40 degrees C. The mobile phase A consisted of water and 0.1% formic acid. The mobile phase B consisted of methanol and 0.1% formic acid. The analytes were eluted from the column with a linear gradient from 5% B to 80% B in 5 min, then hold for 0.5 min before returning to initial condition. The flow rate was 0.35 mL x min(-1). A tandem mass spectrometer equipped with electrospray ionization source was used as detector. Multiple reaction monitoring (MRM) using the precursor to product ion pairs of m/z 447-->271 (for baicalin), m/z 353-->191 (for chlorogenic acid) and m/z 287-->287 (for internal standard) were used to quantification. The linear concentration ranges of the calibration curves for baicalin and chlorogenic acid ranged from 9.6 to 1540 ng x mL(-1) and from 7.5 to 1200 ng x mL(-1), respectively. The intra- and inter-day relative standard deviation (RSD) across three validations run over the entire concentration range was less than 10.2% for both baicalin and chlorogenic acid. After iv infusion of Yinhuang injection to the volunteers, the concentration-time curves of baicalin and chlorogenic acid fitted the two-compartment and three-compartment model. T(1/2)alpha were (4.47 +/- 0.89) and (7.65 +/- 4.42) min, T(1/2)beta were (46.22 +/- 10.03) and (34.40 +/- 19.16) min, respectively. The method was proved to be highly sensitive, selective, and suitable for pharmacokinetic investigations of both baicalin and chlorogenic acid.
Area Under Curve
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Chlorogenic Acid
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blood
;
pharmacokinetics
;
Chromatography, Liquid
;
methods
;
Drug Combinations
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Drugs, Chinese Herbal
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administration & dosage
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isolation & purification
;
pharmacokinetics
;
Female
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Flavonoids
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blood
;
pharmacokinetics
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Humans
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Injections, Intravenous
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Lonicera
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chemistry
;
Male
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Plants, Medicinal
;
chemistry
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Scutellaria baicalensis
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chemistry
;
Spectrometry, Mass, Electrospray Ionization
;
methods
;
Tandem Mass Spectrometry
;
methods
;
Young Adult
9.Albumin kinetics in patients with severe sepsis.
Wei-qin LI ; Xin-ying WANG ; Hong ZHU ; Heng-shan TAN ; Jian-zhong RUI ; Yang BAO ; Zhu-fu QUAN ; Ning LI ; Jie-shou LI
Chinese Journal of Surgery 2003;41(6):423-426
OBJECTIVETo explore the mechanism of hypoalbuminemia in patients with severe sepsis.
METHODSI(125)-labeled albumin was administered intravenously to 10 health volunteers and 10 patients with severe sepsis. Blood samples were taken at 0, 1, 2, 4, 8, 12, 24 hours and 2, 3, 4, 5, 6, 7, 9, 11, 13, 15, 18, 22, 25 days for the measurement of the dose of gamma-radiation and the curve of concentration and time. Then the half-life time (t(1/2)), apparent volume of distribution (V(d)) and transportation rate (K(12)) from center compartment to side compartment of albumin were calculated.
RESULTSThe half-life time in septic group was obviously shorter than that in control group (8.2 +/- 1.4 vs. 12.5 +/- 1.7, P < 0.01). The transportation rate in the septic group was higher than that in the control group [(4.4 +/- 1.9) x 10(-2)/h vs. (2.4 +/- 0.6) x 10(-2)/h, P < 0.05]. There was no significant difference in apparent volume of distribution between the two groups.
CONCLUSIONSIn patients with severe sepsis, the distribution rate of albumin from vessel to tissue was obviously increased and the decomposition rate of albumin was markedly improved.
Adult ; Aged ; Female ; Half-Life ; Humans ; Kinetics ; Male ; Middle Aged ; Sepsis ; metabolism ; Serum Albumin ; metabolism
10.Merits of a harmonised system to classify drug-related problems in Singapore.
Tat Ming NG ; Wee Chuan HING ; Tsing Yi KOH ; Wei Terk CHANG ; Grace S W CHANG ; Jian Wei HENG ; Isnarti Bte ABUAMAN ; Beng Yi SIA ; Yik Chuen SAW ; Daphne CHAN ; Chwee Huat TAN ; Wei Shan FAN ; Franky FRANKY ; Poh Ching TAN ; Cheryl W Y TAN ; Joanne H L SNG ; Chun Wei YAP ; Shanti Uma Devi GNANAMANI ; Doreen S Y TAN
Annals of the Academy of Medicine, Singapore 2021;50(7):572-577