1.Determination of yogliptin and its metabolite in Wistar rat plasma by liquid chromatography-tandem mass spectrometry.
Jun-Ting DAI ; Zhi-Yun MENG ; Xiao-Xia ZHU ; Hui GAN ; Ruo-Lan GU ; Bo YANG ; Li-Ying YU ; Gui-Fang DOU
Acta Pharmaceutica Sinica 2014;49(7):1044-1048
A rapid, sensitive and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of yogliptin and its metabolite in Wistar rat plasma. Linagliptin and dexamethasone were chosen as the internal standards of yogliptin and its metabolite, (R)-8-(3-hydroxypiperidine- -yl)-7-(but-2-yn-1-yl)-1-((5-fluorobenzo[d]thiazol-2-yl)methyl)-3-methyl- H-purine-2, 6 (3H, 7H)-dione, respectively. After a simple protein precipitation using acetonitrile as the precipitating solvent, both analytes and ISs were separated on a Grace Altima HP C18 column (2.1 mm x 50 mm, 5 microm) with gradient elution using methanol (containing 0.1% formic acid, 4 mmol x L(-1) ammonium acetate)-0.1% formic acid (containing 4 mmol x L(-1) ammonium acetate) as the mobile phase. A chromatographic total run time of 4.4 min was achieved. Mass spectrometric detection was conducted with electrospray ionization under positive-ion and multiple-reaction monitoring modes. Linear calibration curves for yogliptin and its metabolite were over the concentration range of 0.5 to 500 ng x mL(-1) with a lower limit of quantification of 0.5 ng x mL(-1). The intra- and inter- assay precisions were all below 14%, the accuracies were all in standard ranges. The method was used to determine the concentration of yogliptin and M1 in Wistar rat plasma after a single oral administration of yogliptin (27 mg x kg(-1)). The method was proved to be selective, sensitive and suitable for pharmacokinetic study of yogliptin and M1 in Wistar rat plasma.
Animals
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Chromatography, Liquid
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Dexamethasone
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blood
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Dipeptidyl-Peptidase IV Inhibitors
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blood
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pharmacokinetics
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Linagliptin
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blood
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Rats
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Rats, Wistar
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Tandem Mass Spectrometry
2.Analysis of tear film and corneal endothelial cell density in cataract patients with high myopia
Qi RUO ; Zhou LI-XIAO ; Gu ZHI-MIN ; Huo YIN-PING
International Eye Science 2017;17(11):2081-2084
AIM:To observe the tear film and corneal endothelial cell density in cataract patients with high myopia.METHODS:From January 2016 to December 2016,38 cases (38 eyes) with high myopia and cataract were selected as study group,24 males (24 eyes) and 14 females (14 eyes),average 65.2±2.37(60-72) years old.Age-related cataract patients without high myopia were as control group,22 males (22 eyes) and 16 females (16 eyes),average 64.4±2.43 (61-70) years old.The tear film and corneal endothelial cell density of the two groups were observed at 3,7,14d and 1mo after operations.RESULTS:Between the two groups of preoperative S I t,BUT,FL,subjective rating,corneal endothelial cell density comparison,there were no statistically significant difference (P>0.05).In the two groups at 3,7,14d and 1mo after operations,BUT,FL,corneal endothelial cell density,subjective score comparison,the difference had statistical significance (P<0.01).Two groups after 3,7,14d comparative differences of S Ⅰ t were statistically significant (P < 0.01),not statistical significant at postoperative 1mo (P>0.05).At postoperative 3,7,14d,1mo,FL,subjective rating,corneal endothelial cell density of the two groups were compared with preoperative,the difference was statistically significant (P<0.01).In the two groups at 3,7,14d after operation,S I t compared with the same group preoperative difference was statistically significant (P < 0.01),no statistical significance when postoperative 1mo compared with preoperative (P>0.05).BUT of high myopia patients with age-related cataract surgery,at 3,7,14d and 1mo after operations decreased than preoperative,the difference was statistically significant (P< 0.01).Age-related cataract patients without high myopia at 3,7,14d after operation decreased than preoperative,the difference was statistically significant (P<0.01),there was no statistically significant difference between preoperative and postoperative 1 mo (P>0.05).CONCLUSION:Phacoemulsification cataract surgery in the treatment of high myopia cataract patients is safe and reliable,and less influence on tear film and corneal endothelial cell density.
3.Histone acetylation and expression of acetylation-related enzymes in children with tetralogy of Fallot.
Jun XU ; Yi-Xiang LIN ; Ruo-Yi GU ; Hui-Jun WANG ; Xiao-Jing MA ; Duan MA ; Guo-Ying HUANG
Chinese Journal of Contemporary Pediatrics 2013;15(10):817-821
OBJECTIVETo study the expression of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in children with tetralogy of Fallot (TOF), and to investigate the role of histone acetylation and acetylation-related enzymes in the pathogenesis of TOF.
METHODSMyocardial tissue samples in the TOF group were obtained from 46 children with TOF who underwent radical operation, and myocardial tissue samples in the control group were obtained from 16 children who suffered accidental deaths and had no cardiac anomalies as shown by autopsy. The acetylation of H3K9, H3K18 and H3K27 was evaluated by immunohistochemistry. The mRNA expression of HATs and HDACs in the myocardium was measured by real-time PCR. The correlation between mRNA expression of HATs and HDACs and histone acetylation was analyzed.
RESULTSCompared with the control group, the TOF group showed significantly increased acetylation of H3K9 (P=0.0165) and significantly decreased acetylation of H3K18 (P=0.0048) and H3K27 (P=0.0084). As to 4 HATs and 6 HDACs, the mRNA expression of EP300 and CBP was significantly higher in the TOF group than in the control group (P=0.025; P=0.017), and there was no significant difference in the mRNA expression of other HATs and HDACs between the two groups. The correlation analysis revealed a positive correlation between H3K9 acetylation and mRNA expression of EP300 (r=0.71, P<0.01) and CBP (r=0.72, P<0.01).
CONCLUSIONSUpregulated mRNA expression of EP300 and CBP may be associated with increased H3K9 acetylation, suggesting that EP300 and CBP might affect cardiac development by regulating H3K9 acetylation.
Acetylation ; E1A-Associated p300 Protein ; genetics ; Female ; Histone Acetyltransferases ; genetics ; Histone Deacetylases ; genetics ; Histones ; metabolism ; Humans ; Infant ; Male ; Myocardium ; metabolism ; Peptide Fragments ; genetics ; RNA, Messenger ; analysis ; Sialoglycoproteins ; genetics ; Tetralogy of Fallot ; metabolism
4.Pharmacokinetics of two recombinant humanized monoclonal antibodies against ricin in rhesus monkeys
Ya GAO ; Xiao-xia ZHU ; Zhi-yun MENG ; Hui GAN ; Ruo-lan GU ; Zhuo-na WU ; Wen-zhong SUN ; Gui-fang DOU
Acta Pharmaceutica Sinica 2022;57(2):480-483
Recombinant humanized anti-ricin monoclonal antibody (MIL50) is a recombinant humanized monoclonal antibody targeting ricin. In this study, an ELISA method was used to establish a method for the determination of MIL50 in macaque serum, and a cross design method was used. Twelve rhesus monkeys were intravenously injected 1 mg·kg-1 test preparation (MIL50 freeze-died powder injection) and reference preparation (MIL50 liquid preparation) to determine the plasma concentration of MIL50 at different time points, and the pharmacokinetic parameters were analyzed to compare the pharmacokinetic characteristics of MIL50 liquid preparation and freeze-died powder injection in rhesus monkeys. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Chinese Academy of Medical Sciences and Use of Laboratory Animals and the regulations derived by the Animal Care and Welfare Committee of the Institute of Radiation Medicine, Academy of Military Medical Sciences (IACUC-DWZX-2020-503). The results showed that there was no significant difference between
5.Correlation study of auto-immune antibodies and rheumatoid arthritis patients of Shen deficiency syndrome.
Lin-Kai GUO ; Shi-Zhi LUO ; Qian-Hua LIAO ; Ruo-Gu LAI ; Xiao-Ling LIU ; Li-Juan LIU ; Guang-xing CHEN
Chinese Journal of Integrated Traditional and Western Medicine 2013;33(5):619-622
OBJECTIVETo investigate the correlation between auto-immune antibodies and rheumatoid arthritis (RA) patients of Shen deficiency syndrome (SDS), thus providing clinical evidence for further researches on molecular biological mechanisms of RA patients of SDS.
METHODSTotally 451 RA patients were assigned to the SDS group and the non-SDS group. Their general conditions (including gender, age, duration, and age of onset), C reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet (PLT), disease activities (DAS28), auto-antibodies [rheumatoid factor (RF), anti-CCP antibodies, anti-nuclear antibody (ANA)] were compared between the two groups.
RESULTS(1) The scores for EST, PLT, and DAS28 were obviously higher in the SDS group than in the non-SDS group (P < 0.05, P <0. 01). (2) The level of average RF was (697.32 +/-1 061.38 IU/mL) in the SDS group, higher than that in the non-SDS group (439.91 +/- 672.24 IU/mL, P <0.01). There was no statistical difference in anti-CCP antibody between the two groups (P >0.05).(3) The ANA positive rate of RA patients was 29. 63% (120/405). It was 37.19% (74/199) in RA patients of SDS and 22. 33% (46/206) in RA patients of non-SDS, showing statistical difference between the two groups (P <0.01). (4) The odds ratio for high level RF positive and ANA positive was 1. 574 and 2. 059 folds in RA patients of SDS as high as that in RA patients of non-SDS.
CONCLUSIONSRA patients of SDS would have higher risk of having auto-immune antibodies, fastened development, more worsen joint damage, and more poor prognosis. Its mechanisms might be closely associated with autoimmune tolerance.
Adolescent ; Adult ; Aged ; Arthritis, Rheumatoid ; blood ; diagnosis ; Autoantibodies ; blood ; Child ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Young Adult
6.Pharmacodynamics and pharmacokinetics of batroxobin in Beagle dog.
Zi-Hua ZHENG ; Xiao-Xia ZHU ; Hui GAN ; Ruo-Lan GU ; Zhuo-Na WU ; Zhi-Yun MENG ; Gui-Fang DOU
Acta Pharmaceutica Sinica 2013;48(8):1307-1311
Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.
Animals
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Area Under Curve
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Batroxobin
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administration & dosage
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blood
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pharmacokinetics
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pharmacology
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Dogs
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Enzyme-Linked Immunosorbent Assay
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Fibrin Fibrinogen Degradation Products
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metabolism
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Fibrinogen
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metabolism
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Fibrinolytic Agents
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administration & dosage
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blood
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pharmacokinetics
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pharmacology
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Infusions, Intravenous
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Male
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Partial Thromboplastin Time
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Prothrombin Time
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Thrombin Time
7.Correlation research on the expression of FcgammaR II b on B cells and rheumatoid arthritis patients of Shen deficiency syndrome.
Qian-Hua LIAO ; Lin-Kai GUO ; Shi-Zhi LUO ; Ruo-Gu LAI ; Xiao-Ling LIU ; Guang-Xing CHEN
Chinese Journal of Integrated Traditional and Western Medicine 2013;33(9):1203-1207
OBJECTIVETo study the correlation between the expression of Fcgamma receptor II b (FcgammaRII b) on B cells and rheumatoid arthritis (RA) patients of Shen deficiency syndrome (SDS).
METHODSThere were 43 RA patients, including 26 of SDS and 17 of non-SDS. The expression levels of FcgammaRII b on naive B cells, memory B cells, and plasma blasts in the peripheral blood were detected by flow cytometry. The numbers of tender joints, numbers of swollen joints, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and disease activity score (DAS28), the correlation between the distribution of B cells and the expression level of FcgammaRII b in RA patients were analyzed. Besides, another 21 healthy volunteers were recruited as the control group.
RESULTSThe expression level of FcgammaRII b was 49.65% +/- 15.86% on memory B cells and 43.69% +/- 22.57% on plasma blasts in RA patients of SDS, significantly down-regulated when compared with those of the control group (64.03% +/- 6.01%, 66.59% +/- 10.18%, P < 0.01). The expression level of FcgammaRII b on memory B cells of RA patients of non-SDS was down-regulated more obviously when compared with that of the control group (52.70% +/- 9.52% versus 64.03% +/- 6.01%, P < 0.01). The expression level of FcgammaRII b on plasma blasts was obviously lower in RA patients of SDS than in RA patients of non-SDS (56.10% +/- 17.05%, P < 0.05). The expression level of FcgammaRII b on memory B cells was not correlated with numbers of tender joints, numbers of swollen joints, ESR, RF, or DAS28.
CONCLUSIONSThe defective immunological tolerance of B cells in RA patients of SDS might be closely correlated with down-regulation of FcgammaRII b on memory B cells and plasma blasts. There might exist genetic abnormality of FcgammaRII b gene in RA patients of SDS, thus inducing loss of autoimmunity tolerance.
Adult ; Arthritis, Rheumatoid ; blood ; diagnosis ; immunology ; B-Lymphocytes ; immunology ; metabolism ; Case-Control Studies ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Receptors, IgG ; immunology ; metabolism
8.Chinese Systemic Lupus Erythematosus Treatment and Research Group Registry IX: Clinical Features and Survival of Childhood?Onset Systemic Lupus Erythematosus in China
Wu CHAN?YUAN ; Li CAI?FENG ; Wu QING?JUN ; Xu JIAN?HUA ; Jiang LIN?DI ; Gong LU ; Wu FENG?QI ; Gu JIE?RUO ; Zhao JIU?LIANG ; Li MENG?TAO ; Zhao YAN ; Zeng XIAO?FENG
Chinese Medical Journal 2017;(11):1276-1282
Background: Approximately 15–20% cases of systemic lupus erythematosus (SLE) are diagnosed in children. There have been a few studies reporting the epidemiological data of pediatric?onset SLE (cSLE) in China, neither comparing the differences between cSLE and adult?onset SLE (aSLE). The aim of this study was to describe the impact of age of onset on clinical features and survival in cSLE patients in China based on the Chinese SLE Treatment and Research group (CSTAR) database. Methods: We made a prospective study of 225 cSLE patients (aged <16 years) and 1759 patients aged 16–50 years based on CSTAR registry. We analyzed initial symptoms, clinical presentations, SLE disease activity, damages, and outcomes of cSLE, as well as compared with aSLE patients. Results: The mean age of cSLE patients was 12.16 ± 2.92 years, with 187 (83.1%) females. Fever (P < 0.001) as well as mucocutaneous (P < 0.001) and renal (P = 0.006) disorders were found to be significantly more frequent in cSLE patients as initial symptoms, while muscle and joint lesions were significantly less common compared to aSLE subjects (P < 0.001). The cSLE patients were found to present more frequently with malar rash (P = 0.001; odds ratio [OR], 0.624; 95% confidence interval [CI ], 0.470–0.829) but less frequently with arthritis (P < 0.001; OR, 2.013; 95% CI, 1.512–2.679) and serositis (P = 0.030; OR, 1.629; 95% CI, 1.053–2.520). There was no significant difference in SLE disease activity index scores between cSLE and aSLE groups (P = 0.478). Cox regression indicated that childhood onset was the risk factor for organ damage in lupus patients (hazard ratio 0.335 [0.170–0.658], P = 0.001). The survival curves between the cSLE and aSLE groups had no significant difference as determined by the log?rank test (0.557, P = 0.455). Conclusions: cSLE in China has different clinical features and more inflammation than aSLE patients. Damage may be less in children and there is no difference in 5? year survival between cSLE and aSLE groups.
9.Correlation between birth defects and dietary nutrition status in a high incidence area of China.
Bao-Yuan ZHANG ; Ting ZHANG ; Liang-Ming LIN ; Fang WANG ; Ruo-Lei XIN ; Xue GU ; Yu-Na HE ; Dong-Mei YU ; Pei-Zhen LI ; Qing-Shan ZHANG ; Jin ZHAO ; Yu-Fu QIN ; Xiu-Feng YANG ; Gong CHEN ; Ju-Fen LIU ; Xin-Ming SONG ; Xiao-Ying ZHENG
Biomedical and Environmental Sciences 2008;21(1):37-44
OBJECTIVETo investigate the association between birth defects and dietary nutrient intake in a high risk area of China.
METHODSA dietary survey was performed and serum folic acid was measured in women whose pregnancy was affected by neural tube defects (NTDs) or unaffected by any birth defects (BDs) in Zhongyang and Jiaokou Counties in Shanxi Province of China.
RESULTSThe local average consumption of foods including dark green vegetables, fruits, fat and meat, and nutrient intake (e.g., energy, protein, retinol, riboflavin, vitamin E, and selenium) were lower than the national average level. In women of childbearing age, these regions, the intake of nutrients was much lower than the recommended nutrient intake (9%-77%). The case-control dietary nutrition study of women whose pregnancy was affected by BDs (including NTDs and congenital heart defects) demonstrated that, in early pregnancy, adequate nutrition (i.e., eating meat, fresh vegetables, fruit more than once a week) was a protective factor, while eating germinated potatoes was a risk factor. The geometrical mean (p5-p95) of serum folic acid in women with NTD birth defects was 9.6 nmol/L (3.6, 23.03), which was significantly lower than that in normal women (14.03 nmol/L).
CONCLUSIONWomen of childbearing age in the two counties of Shanxi Province, China, have a marked insufficient intake of some nutrients, especially folic acid, zinc, vitamins A and B12. This nutrient deficiency may be an important risk factor for the high prevalence of birth defects in these regions. Therefore, adequate dietary nutrition in early pregnancy can prevent BDs.
Adolescent ; Adult ; Aged ; Case-Control Studies ; China ; epidemiology ; Female ; Folic Acid ; blood ; Humans ; Incidence ; Middle Aged ; Neural Tube Defects ; epidemiology ; Nutritional Status ; Surveys and Questionnaires
10.Etoricoxib versus indometacin in the treatment of Chinese patients with acute gouty arthritis: a randomized double-blind trial.
Ting LI ; Shun-le CHEN ; Qing DAI ; Xing-Hai HAN ; Zhan-Guo LI ; Dong-Hai WU ; Xiao ZHANG ; Jie-Ruo GU ; Nan-Ping YANG ; Ling-Yun SUN ; Miu-Jia ZHANG ; Xing-Fu LI ; Chun-de BAO
Chinese Medical Journal 2013;126(10):1867-1871
BACKGROUNDAcute gout is an intensely painful, inflammatory arthritis. Although the non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for this condition, the efficacy is based on only a few studies, particularly in China. We tried to assess the safety and efficacy of etoricoxib in the treatment of acute gouty arthritis in China.
METHODSA randomized, double-blind, active comparator study was conducted at 10 sites in China. Patients (n = 178; ≥ 18 years of age) with acute gouty attack (< 48 hours) were treated for 5 days with etoricoxib (120 mg/d; n = 89) or indometacin (75 mg twice daily; n = 89). The primary efficacy end point was self-assessed pain in the affected joint (0-4 point Likert scale) from days 2 - 5. Secondary end points included investigator assessments of tenderness and swelling, patient/ investigator global assessments of response to therapy, and patients discontinuing treatment. Safety was assessed by adverse events (AEs).
RESULTSEtoricoxib and indometacin had comparable primary and secondary end points. Mean change difference from baseline from days 2 - 5 was 0.03 (95% confidence interval (CI) -0.19 to 0.25; P = 0.6364), which fell within the prespecified comparative bounds of -0.5 to 0.5. No severe AEs were associated with etoricoxib use. Non-severe AEs were mainly digestive and general, and most (73.7%) were mild, although they caused withdrawal of two subjects in the etoricoxib group, due to bilateral renal calculi and uronephrosis of the left kidney (unrelated to etoricoxib) and fever and chills (potentially etoricoxib-related). Overall, AEs were similar, although the absolute number of AEs in the etoricoxib group (n = 31) was less than the indometacin group (n = 34).
CONCLUSIONSEtoricoxib (120 mg once daily) is effective in treating acute gout, is generally safe and well-tolerated, and is comparable in efficacy to indometacin (75 mg twice daily).
Adult ; Aged ; Arthritis, Gouty ; drug therapy ; Cyclooxygenase Inhibitors ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Humans ; Indomethacin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Pyridines ; adverse effects ; therapeutic use ; Sulfones ; adverse effects ; therapeutic use