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A pharmacokinetic study of Isatin in Beagles' bodies
Ren, AL;Su, BH;Ye, SY;Wei, X;Fang, ZG;Wang, Q;Zhang, J;Xu, W;Yue, W;Yin, L;Liu, ZT;Li, XL;Ding, B
EXPERIMENTAL AND THERAPEUTIC MEDICINE 2016年 11卷6期 页码:2225-2228
INHIBITOR
Isatin are marine active drugs that exert anti-cancer effects, have a cancer-prevention function, and possess many pharmacological activities. The study aimed to examine the pharmacokinetics of a single intravenous injection and oral medication of Isatin given to Beagles. Nine male and nine female Beagles were injected with 30 mg/kg of 2,3-indole quinones. The animals were divided into 3 groups (n=6 per group) and lavaged with a dose of 15, 30 and 60 mg/kg, respectively. Blood samples were collected prior to the medicine delivery (0 h) and 0.083, 0.25, 0.5, 1, 2, 4, 6, 8 and 24 h post-medicine delivery. The blood plasma samples were analyzed using the liquid chromatography-mass spectrometry (MS)/MS method following pretreatment for the protein precipitation. Pharmacokinetics software was applied to calculate relevant pharmacokinetic parameters through the atrioventricular model. The drug concentration in plasma decreased rapidly following the intravenous injection of Isatin. After 8 h, the prototype drugs could not be tested in the plasma and only trace amounts of drugs were tested in one dog, which was considered to be an endogenous drug. Indole quinone was absorbed following lavage into Beagles and peaked in <1 h, and the drug concentration in the plasma decreased rapidly. After 8 h, the prototype drugs could not be tested in the plasma. The elimination of the two drugs in the body had no evident gender differences. In conclusion, Isatin is rapidly absorbed in bodies of Beagles. Within the dose range of 15-60 mg/kg, no linear relationship was observed for the increase in Cmax and AUC(0-t) values with the increased dose.
Pharmacokinetic study of isatin in dog plasma by liquid chromatography tandem mass spectrometry
Ren, A;Wang, Q;Fang, Z;Gao, M;Wang, H;Zhang, J;Xu, W;Yue, W;Yin, L;Liu, Z;Li, X;Ding, B
PANMINERVA MEDICA 2015年 57卷4期 页码:177-182
URINE; INHIBITOR; BRAIN
Aim. A sensitive and selective method was developed and validated to study the pharmacokinetics of isatin.;-;Methods. The blood samples were pretreated by protein precipitation method using methanol. Quetiapine was used as an internal standard. After pretreatment, the samples were assayed by LC/MS/NIS method and the pharmacokinetic parameters were calculated by WinNonlin 5.2 using non-compartment model. The separation was performed on a Venusil XBP PH column (5 mu m, 2.0x100 mm) with an isocratic mobile phase consisted of methanol-water (containing 50 mM ammonium formate) (65:35, v/v) at a flow rate of 0.3 mL/min. The Agilent G6410B triple quadrupole LC/MS system was operated under the multiple reactions monitoring mode (MRM) using the electrospray ionization technique in positive mode.;-;Results. The lower limits of quantification (LLOQ) of the analyte of the method was 10 ng/mL. The method was linear with correlation coefficient >0.995. The intraday and inter day accuracy and precision of the assay were acceptable.;-;Conclusion. This method has been applied successfully to a pharmacokinetic study involving the oral and intravenous administration of isatin to beagle dogs.
Association between Leukocyte and Metabolic Syndrome in Urban Han Chinese: A Longitudinal Cohort Study
Meng, WJ;Zhang, CQ;Zhang, Q;Song, XH;Lin, HY;Zhang, DZ;Zhang, YY;Zhu, ZX;Wu, S;Liu, YX;Tang, F;Yang, XW;Xue, FZ
PLOS ONE 2012年 7卷11期 影响因子:3.057
BLOOD-CELL COUNT; C-REACTIVE PROTEIN; MALE OFFICE WORKERS; INSULIN-RESISTANCE; ADIPOSE-TISSUE; MACROPHAGE POLARIZATION; INFLAMMATION; POPULATION; JAPANESE; RISK
Background: Although cross-sectional studies have shown that leukocyte is linked with metabolic syndrome (MetS), few longitudinal or cohort studies have been used to confirm this relationship. We therefore conducted a large-scale health check-up longitudinal cohort in urban Chinese population from middle to upper socioeconomic strata to investigate and prove the association between the total leukocyte/its subtypes and MetS/its components (obesity, hyperglycemia, dyslipidemia, and hypertension).;-;Methods: A longitudinal cohort study was established in 2005 on individuals who were middle-to-upper class urban Chinese. Data used in this investigation was based on 6,513 participants who had at least three routine health check-ups over a period of six-year follow-up. Data analysis was conducted through generalized estimating equation (GEE) model.;-;Results: A total of 255 cases of MetS occurred over the six-year follow-up, leading to a total incidence density of 11.45 per 1,000 person-years (255/22279 person-years). The total leukocyte was markedly associated with MetS (RR = 2.66, 95%CI = 1.81-3.90], p < 0.0001) and a dose-response existed. Similar trends can be found in monocytes, lymphocytes, and neutrophils compared with the total leukocyte. The total leukocyte, neutrophil, monocyte and eosinophil levels were strong and independent risk factors to obesity, total leukocyte and neutrophil to dyslipidemia and hyperglycemia, while neither total leukocyte nor its subtypes to hypertension.;-;Conclusion: Total leukocyte/its subtype were associated with MetS/its components (obesity, dyslipidemia and hyperglycemia), they might provide convenient and useful markers for further risk appraisal of MetS, and be the earlier biomarkers for predicting cardiovascular disease than the components of MetS.
Thyroid-Stimulating Hormone Levels within the Reference Range Are Associated with Serum Lipid Profiles Independent of Thyroid Hormones
Wang, FR;Tan, YY;Wang, CG;Zhang, X;Zhao, YF;Song, XH;Zhang, BC;Guan, QB;Xu, J;Zhang, J;Zhang, DZ;Lin, HY;Yu, CX;Zhao, JJ
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 2012年 97卷8期 页码:2724-2731
CORONARY-HEART-DISEASE; HEALTHY EUTHYROID SUBJECTS; SUBCLINICAL HYPOTHYROIDISM; INSULIN SENSITIVITY; METABOLIC SYNDROME; FREE TRIIODOTHYRONINE; THYROTROPIN LEVELS; FREE-THYROXINE; RISK-FACTORS; OBESE WOMEN
Context and Objective: Dyslipidemia in thyroid dysfunction has always been attributed to changes in thyroid hormone (TH) levels. We hypothesized that TSH plays an important role in lipid metabolism independent of TH.;-;Design and Setting: We conducted a cross-sectional study to investigate the relationship between serum TSH levels and lipid profiles after controlling for free T-3, free T-4, total T-3, total T-4 and nonthyroid factors relevant to lipid metabolism in euthyroid Chinese subjects.;-;Main Outcome Measures: General linear analysis was performed to determine whether the impact of TSH on serum lipid levels is independent of the TH levels. Moreover, path analysis, an evolutionary multivariable regression technique, was conducted to test whether there is a direct and/or indirect effect between serum TSH and total cholesterol (TC) levels. Additionally, the odds ratios (95% confidence interval) for hypercholesterolemia in relation to TSH categories were calculated.;-;Results: A total of 3664 euthyroid subjects were finally analyzed. There was a significant linear trend toward higher log TC (P = 0.021) and log triglyceride (P = 0.001) levels with increasing serum TSH levels within the reference range, which remained significant after adjusting for factors such as TH levels, age, and smoking. Most importantly, the total effect of TSH on TC levels (total effect(TC,) (TSH) = 0.05253) includes a direct effect (direct effect(TC,) (TSH) = 0.05979) and an indirect effect via TH. Compared with subjects in the lower part of the reference range (TSH level, 0.27-0.61 mIU/liter), the adjusted odds ratio for hypercholesterolemia was 3.239 (95% confidence interval, 1.392-7.538; P = 0.007) for those in the upper category (TSH level, 4.61-5.5 mIU/liter).;-;Conclusions: The variation in normal TSH levels is partially related to the lipid components and hypercholesterolemia in euthyroid subjects and includes both TH-dependent and TH-independent effects. Our study suggests the importance of controlling TSH in hypothyroid subjects. (J Clin Endocrinol Metab 97: 2724-2731, 2012)
A longitudinal cohort based association study between uric acid level and metabolic syndrome in Chinese Han urban male population
Zhang, Q;Zhang, CQ;Song, XH;Lin, HY;Zhang, DZ;Meng, WJ;Zhang, YY;Zhu, ZX;Tang, F;Liu, LJ;Yang, XW;Xue, FZ
BMC PUBLIC HEALTH 2012年 12卷
CARDIOVASCULAR-DISEASE; RISK-FACTORS; GENERAL-POPULATION; INNOCENT BYSTANDER; HYPERURICEMIA; INSULIN; GLUCOSE; ADULTS; MEN; HYPERTENSION
Background: It has been recently demonstrated that serum uric acid (UA) is associated with metabolic syndrome (MetS) or its related clinical indications based on cross-sectional or prospective cohort studies. Nonetheless, due to the fact that UA level constantly fluctuates from time to time even for the person, using a single measure of UA level at baseline of those studies may not be sufficient for estimating the UA-Mets association.;-;Methods: To further estimate this time-dependent association, we fitted a generalized estimating equation (GEE) regression model with data from a large-scale 6-year longitudinal study, which included 2222 participants aged > = 25 years with an average of 3.5 repeated measures of UA per person in the Health Management Center of Shandong Provincial Hospital, Shandong, China.;-;Results: After adjusting for other potential confounding factors (i. e., total cholesterol, low-density lipoprotein), it was verified that time-dependent UA level was an independent risk factor for MetS (OR = 1.6920, p < 0.0001). It was found that UA level was positively associated with obesity, hypertension, and dyslipidemia, but was inversely associated with hyperglycemia.;-;Conclusions: Serum UA level may serve as an important risk factor of MetS. Additionally, our study suggested that UA level be an independent risk factor to obesity, hypertension and dyslipidemia, but a protective factor to hyperglycemia. These findings are concordant with results from other studies on Asian populations, and jointly provide a basis to further develop a risk assessment model for predicting MetS using UA levels and other factors in China.
Distribution of serum prostate-specific antigen in Chinese healthy men: a population-based study
Yuan, XD;Dong, ZG;Zhang, H;Lin, HY;Song, XH;Niu, ZH;Fu, Q;Liu, S;Sun, ZJ;Lu, JJ
CHINESE MEDICAL JOURNAL 2011年 124卷8期 页码:1189-1192
COMMUNITY-BASED POPULATION; REFERENCE RANGES; PSA MEASUREMENTS; WHITE MEN; CANCER; ESTABLISHMENT; MORTALITY; TRIAL
Background The morbidity and mortality of prostate cancer have been increasing rapidly in recent China. There were few studies investigating prostate-specific antigen (PSA) values ranges in the healthy Chinese population. We performed this study to determine the distribution of serum PSA in a large healthy Chinese population.;-;Methods From January 2001 to May 2008, 11 150 healthy Chinese men aged 30-79 years came to our hospital for routine health check-up. All subjects without a previous diagnosis of prostate cancer, a history of prostate surgery, or urogenital tract infection were proposed to undergo systematic serum PSA measurement and digital rectal examination (DRE). Men with normal DRE and PSA <= 4.0 ng/ml and those PSA >4.0 ng/ml or abnormal DRE but without adverse findings on prostate biopsy were included (n=9358). Age and serum PSA concentration were recorded and correlated through Logistic regression analysis.;-;Results The 95th percentile serum PSA concentration was 1.89 ng/ml for men aged 30 to 39 years, 2.19 ng/ml for men aged 40 to 49 years, 2.88 ng/ml for men aged 50 to 59 years, 4.42 ng/ml for men aged 60 to 69 years, and 6.52 ng/ml for men aged 70 to 79 years. The serum PSA concentration correlated with age (P <0.0001) with an annual increase of 0.97% for men in 40 years, 1.58% for men in 50 years, 3.04% for men in 60 years, and 3.99% for men in 70 years.;-;Conclusions The serum PSA level correlates directly with age in Chinese men older than 40 years, not in Chinese men younger than 40 years old. Chinese men have lower PSA level compared with white men above 60 years of age, not in those under 60 years of age. Chin Med J 2011;124(8):1189-1192
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