1.Effect of CYP3A5 and CYP3A4 on pharmacokinetics of Tacrolimus in renal transplantation recipients
Ling LIN ; Wenli SONG ; Zhongyang SHEN ; Yi ZHANG
Chinese Journal of Organ Transplantation 2012;33(4):220-224
Objective To retrospectively investigate the effects of CYP3A5 * 3,CYP3A4 * 18B and CYP3A5-CYP3A4 phenotype on the C0,D and C0/D of tacrolimus (Tac) in renal transplantation recipients.Methods The CYP3A5 * 3 and CYP3A4 * 18B genotypes of the 61 patients were detected by DNA direct sequencing,and the C0 was detected by ELISA.The differences of C0,D and C0/D on the day 14,and month 1,2 and 3 after transplantation were compared among different genotypes of recipients treated with Tac.Results The frequency of the CYP3A5 * 3 and CYP3A4 * 18B was 74.6% and 26.2% respectively.When the D of the recipients with CYP3A5 * 1 ( * 1/* 1 + * 1/* 3)was 1.3-1.6 times to theCYP3A5*3/*3,theC0 of *3/*3 group was 1.1-1.5 times to the * 1group,and the C0/D was 1.8 2.4 times to the CYP3A5 * 1.For CYP3A4,the D of CYP3A4 * 18B group ( * 1/* 18B+ * 18B/* 18B) was 1.2-1.5 times to the CYP3A5 * 1/* 1,but the C0 of 1/* 1was 1.2-1.4 times to the * 18B,the C0/D was 1.5-1.8 times to the * 18B.For the CYP3A5 CYP3A4 phenotype,the D of the recipients with AAAA was 1.3-1.7 times to the GG-GG,the C0 of GG-GG was 1.5-2 times to the AA-AA,the C0/D of the recipients with G@GG was 2.5-3 times to the AA-AA.In the recipients with C0/D above or below the median of C0/D,the distribution of CYP3A5,CYP3A4 and CYP3A5-CYP3A4 phenotypes was different significantly.Conclusion There is a significant correlation between the CYP3A5,CYP3A4 and pharmacokinetics of Tac.It's more powerful evaluating the CYP3A5-CYP3A4 phenotype rather than just one genotype of the recipients.So detecting the CYP3A5 * 3 and CYP3A4 * 18B genotypes prior to transplantation is meaningful for us to determine an appropriate initial and long-time dosage of Tac.
2.Leaf photosynthetic characteristics and its response for light intensity of three species of Dendrobium Sw.in Huoshan County
Yongping CAI ; Ling LI ; Hesheng LI ; Bingshan LUO ; Yi LIN
Chinese Traditional and Herbal Drugs 1994;0(04):-
Objective To investigate the suitable light intensity of plant growth of Dendrobium Sw.through study on photosynthetic characteristics.Methods The photosynthesis curves of light intensity, chlorophyll fluorescence parameter of different light intensity and inductivity of non-photochemical quenching of chlorophyll fluorescence in 3.0?104 lx on three species of Dendrobium Sw.in Huoshan (D.huo- shanens, D.candium, and D.moniliforme) were determined.Results Three species of Dendrobium Sw.were shadow plants for their response on light intensity, light saturation point, light compensate point, net photosynthesis rate, and apparent quantum efficiency are lower during photosynthesis.The photoinhibitory effect was formed on Dendrobium Sw.leaf when they grew in more than 4.0?104 lx.Conclusion Although three species of Dendrobium Sw.in Huoshan grow in (0.2-2.0)?104 lx normally, they are suitable to grow in (2.5-3.0)?104 lx instead of growing more than 4.0?104 lx.
3.The characteristic of left ventricular twist changed from infancy to the elder assessed by speckle tracking echocardiography
Yi ZHANG ; Qichang ZHOU ; Lin ZOU ; Ling LI ; Yi TAN ; Danming CAO ; Leiqi TIAN
Chinese Journal of Ultrasonography 2008;17(5):369-373
Objective To assess the characteristic of left ventricular(LV) twist changed from infancy to the elder,in order to determine the normal value of LV twist in different age group.Methods After acquired basal and apical LV short-axis images in 293 healthy volunteers (aged 15 days to 72 years) by 2-dimensional echocardiography, speckle tracking echocardiography was used to analysis LV twist motion offline.The peak apical rotation (PAr), peak basal rotation (PBr), peak LV twist (Ptw), peak LV twist normalized by LV length ( PtwN), peak untwisting velocity ( PutwV), isovolumic untwisting% ( Iutw% ) in different group were compared.Results Reliable LV twist measurements were obtained in 274 volunteers.Different LV twist values were noted according to age.Ptw increased gradually with advancing age, when normalized by LV length, PtwN showed higher values before 3 years old and 25 to 45 years old.PutwV increased with aging from infancy to 25 years old, and leveled off from 25 to 45 years old, then decreased with advancing age.Iutw% was lowest before 3 years old,and increased gradually from 25 to 45 years old,then decreased with aging.Conclusions speckle tracking echocardiography can be used to noninvasively and exactly assess LV twist with high feasibility.The effect of aging on LV twist may reflect the process of maturational and adaptive modulation of LV torsional biomechanics from infancy to the elder.
4.Changes of HO-1 genes expression in liver following ischemia/reperfusion of limbs and their significance in rats.
Zhong-Li SHI ; Yi-Ling LING ; Yi-Qun LING ; Yu-Xia YAO ; Jun-Lin ZHOU
Chinese Journal of Applied Physiology 2004;20(4):367-370
AIMTo detect the changes of inducible heme oxygenase (HO-1) expression in liver following ischemia/reperfusion (I/R) of hindlimbs and to elucidate their significance.
METHODSI/R was established using the occlusion of the femoral arteries for 4h and reopening for 2-24 h in rats. The expression of HO-1 mRNA and HO-1 protein in liver tissue were detected with reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical technique, respectively. The observation of pathologic changes of liver was made following the inhibition of HO-1 by zinc protoporphyrin (ZnPP).
RESULTSCompared with control groups, the relative expression level of HO-1 mRNA significantly increased in I/R group. There were more HO-1 positive hepatocytes in I/R group than control groups. The pathologic changes of liver tissue became more severe in I/R + ZnPP group.
CONCLUSIONThe expressions of HO-1 mRNA and protein in liver tissue are significantly upregulated, induction of HO-1 is involved in protection for hepatocytes during the I/R of hindlimbs.
Animals ; Gene Expression ; Heme Oxygenase (Decyclizing) ; genetics ; metabolism ; Hindlimb ; blood supply ; Liver ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism
5.Changes of iNOS genes expression in liver following ischemia and reperfusion of limbs and their significance in rats.
Zhong-li SHI ; Yi-ling LING ; Yu-xia YAO ; Jun-lin ZHOU
Chinese Journal of Applied Physiology 2004;20(2):172-175
AIMTo detect the changes of inducible nitric oxide synthase (iNOS) expression in liver following ischemia/reperfusion (I/R) of hindlimbs and to elucidate their significance.
METHODSI/R was established using the occlusion of the femoral arteries for 4 h and reopening for 2-24 h in rats. The expression of iNOS mRNA, and iNOS protein and the nitrotyrosine (NT), a marker of peroxynitrite (ONOO-), in liver tissue were detected with reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical technique, respectively. The liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) contents were spectrophotometrically measured. The observation of pathologic changes of liver was made following the inhibition of iNOS by aminoguanidine (AG).
RESULTSCompared with control groups, the relative expression level of iNOS mRNA significantly increased in I/R group. There were more iNOS positive hepatocytes and more NT positive hepatocytes in I/R group than control groups. The contents of MDA markedly increased, while the activity of SOD significantly decreased in I/R group, compared with those in the control groups. The pathologic changes of rat liver became milder in I/R group following the inhibition of iNOS by AG.
CONCLUSIONThe expressions of iNOS mRNA and protein in liver are significantly upregulated, excess induction of iNOS-NO is contributed to the liver injury during the I/R of hindlimbs.
Animals ; Guanidines ; pharmacology ; Hindlimb ; blood supply ; Liver ; blood supply ; metabolism ; Male ; Malondialdehyde ; analysis ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; Superoxide Dismutase ; analysis
7.Comparison of the brain pharmacokinetics of nasal tetramethylpyrazine phosphate pH-sensitive in situ gel in normal rats and model rats.
Hong-Wei LIU ; Yi-Lin YAN ; Li-Ling ZHOU
Acta Pharmaceutica Sinica 2012;47(5):677-679
The study is to investigate the brain pharmacokinetics change of nasal tetramethylpyrazine phosphate (TMPP) pH-sensitive in situ gel in normal and model rats. Acute cerebral ischemia rat model was successfully established by middle cerebral artery occlusion (MCAO) method. Both normal and model rats were given nasal TMPP pH-sensitive in situ gel (10 mg x kg(-1)). Perfusates of brain striatum area were collected at each time point by microdialysis. The content of TMPP was determined by HPLC. The pharmacokinetics parameters were calculated by Kinetica 4.4 software at each time point of the brain drug concentration. The main pharmacokinetics parameters of TMPP were fitted with compartments 2. After nasal TMPP pH-sensitive in situ gel the values of C(max) and AUC of both components in brain showed as follows: the value of model group > that of normal group. Significant difference can be observed in the process of brain pharmacokinetics in normal and model rats after giving nasal TMPP pH-sensitive in situ gel.
Administration, Intranasal
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Animals
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Area Under Curve
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Brain
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metabolism
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pathology
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Brain Ischemia
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metabolism
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Chromatography, High Pressure Liquid
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Gels
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Hydrogen-Ion Concentration
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Infarction, Middle Cerebral Artery
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Male
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Microdialysis
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Phosphates
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administration & dosage
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pharmacokinetics
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Pyrazines
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administration & dosage
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pharmacokinetics
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Rats
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Rats, Sprague-Dawley
8.Association analysis of two polymorphisms on chromosome 12p13 to cerebral infarction
Xianjin SHANG ; Yi LIN ; Ling FANG ; Bin CAI ; Wei WEI ; Ning. WANG
Chinese Journal of Neurology 2011;44(9):613-618
ObjectiveTo investigate the association of single nucleotide polymorphisms (SNPs)of rs11833579 and rs12425791 on chromosome 12pl3 with cerebral infarction in the Fujian Han population.MethodsA case-control association study containing a total of 216 cases and 279 controls was carried out.The genotypes of two polymorphisms were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing followed by association analysis.Results The frequency of G > A genotype of rs12425791 in patients with cerebral infarction was lower than that in the controls (34. 3% vs 43.4% , x2 = 4. 298 ,P < 0. 05 ) after stratified by causes of cerebral infarction, there was no significant difference in this genotype between large-artery atherosclerosis and controls.Association analysis was performed by logistic regression model after adjusting by sex, age, hypertension, diabetes mellitus, dyslipidemia, smoking and drinking. Rs12425791 G > A genotype was significantly associated with both cerebral infarction ( OR = 0. 627, 95% CI 0. 417-0. 941, P = 0. 024 ) and large-artery atherosclerosis ( OR =0. 613, 95% CI 0. 396-0. 949 ,P =0. 028). G > A genotype might be a potential protective factor in male( OR =0. 597, 95% CI 0. 364-0. 978, P =0. 041 ). rs11833579 G > A genotype frequency was similar between cases and controls.Conclusion rs12425791 G > A on chromosome 12p13 might be a genetic marker for atherothrombotic brain infarction in Han population of Fujian.
9.Expression and Identification of LfcinB Gene in Pichia pastoris
Jun-Bo YI ; De-Xin HUANG ; Ling-Yun LI ; Feng LIN ;
Microbiology 1992;0(02):-
In present study,bovine Lactoferricin was first secretly expressed in Pichia pastors yeast expression system.The synthesized LfcinB gene fragment was cloned into expression vector pPIC9K,and then obtained recombinant plasmid,designated as pPIC9K-LfcinB,was linearized and transformed into Pichia pastors strains SMD1168 by electroporation.The transformants were screened with Geneticin and multiply-copy colonies were harvested,in which LfcinB gene was verified to inserted into yeast chromosome stably.The positive recombinant Pichia strains were induced with methanol to express LfcinB in culture supernatant.It's expressive products has high activity of killing bacteria.We concluded that LfcinB gene was cloned and integrated into yeast chromosomes,and obtained expression peptide was tested to have high antibacterial activity.
10.Signaling pathways analysis of effects of BSP on RAW264.7 cells proliferation and differentiation
Yu SHI ; Yan ZHANG ; Lisha LIN ; Sinian LIU ; Yi LI ; Chao HAN ; Ling LI
The Journal of Practical Medicine 2016;32(11):1734-1737
Objective To explore the key signaling pathways and molecules of bone sialoprotein (BSP) to promote proliferation and differentiation of preosteoclasts RAW264.7. Methods RAW264.7 cells were treated with BSP and the inhibitors of signaling pathway molecules. MTS and TRAP staining kits were used to evaluate the effects of proliferation and differentiation. The activity assay kits of Calcineurin, AKT, JNK, ERK and p38 were used to detect their activities. Results Inhibiting ERK and p38 can inhibit cell proliferation induced by BSP significantly, while inhibiting AKT, Calcineurin and PI3K can reduce the role of promoting the differentiation by BSP. With increasing treatment time of BSP, the activity of Calcineurin in RAW264.7 cells increased. Furthermore, the activity of AKT was maximum at 48 h after treated with BSP, while the activity of JNK, ERK and p38 were maximum at 24 h after treated with BSP. Conclusions BSP mainly regulates the ERK and p38 of MAPK pathway to promote RAW264.7 cell proliferation, and regulates AKT, PI3K and Calcineurin pathways to promote RAW264.7 cell differentiation.