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1.
Article in English | WPRIM | ID: wpr-878319

ABSTRACT

Objective@#Epidemiological studies reveal that exposure to fine particulate matter (aerodynamic diameter ≤ 2.5 μm, PM @*Methods@#EVs were isolated from the serum of healthy subjects, quantified @*Results@#PM @*Conclusions@#EVs treatment promotes cell survival and attenuates PM


Subject(s)
A549 Cells , Air Pollutants/toxicity , Apoptosis/drug effects , Cell Survival/drug effects , Extracellular Vesicles , Humans , Male , Middle Aged , Particulate Matter/toxicity , Protective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Serum
2.
Acta Pharmaceutica Sinica ; (12): 734-742, 2021.
Article in Chinese | WPRIM | ID: wpr-876527

ABSTRACT

With a deepening understanding of cancer treatment, immune checkpoint inhibitors are recognized widely as a novel fundamental remedy for various malignancies with effectiveness and safety. With the development of pharmacometrics, model-informed drug development (MIDD) has emerged to accelerate the process of clinical research for new drugs and improve the accuracy of decision-making in new drug research, especially for immune checkpoint inhibitors. As a typical illustration, the research development of pembrolizumab is presented in this review to highlight the application of MIDD, which may provide a reference for the development of other new antitumor drugs.

3.
Acta Pharmaceutica Sinica ; (12): 2960-2967, 2020.
Article in Chinese | WPRIM | ID: wpr-862296

ABSTRACT

The goal of this work was to establish a population pharmacokinetics (PPK) model of tacrolimus in idiopathic membranous nephropathy (IMN) patients and to identify potential covariates that influence pharmacokinetic of tacrolimus. A total of 610 data points on the blood concentration of tacrolimus were collected from 96 IMN patients in routine clinical settings. Nonlinear mixed-effect modeling (NONMEM) was used to investigate the effects of CYP3A5 genotype, age, gender, weight, laboratory tests and co-therapy medications on the pharmacokinetic of tacrolimus. The PPK model was evaluated by the goodness-of-fit (GOT), bootstrap and prediction corrected visual predictive check (pc-VPC). The pharmacokinetic of tacrolimus was described by a one-compartment model. The apparent clearance (CL/F) of CYP3A5*1/*3 and *1/*1 were 1.57 and 1.86 times of that of *3/*3, respectively. The CL/F of tacrolimus was 73.6% in patients undergoing co-therapy with Wuzhi capsules, and 1.2 times than that of the patients undergoing co-therapy with Jinshuibao capsules. The evaluation of the model shows that the model is stable and has satisfactory predictive performance. The clinical trial was approved by the Society of Ethics and conducted in Binzhou Medical University Hospital. The established PPK model can describe the pharmacokinetic characteristics of tacrolimus in Chinese patients with IMN, and can facilitate individualized therapy with tacrolimus.

4.
Article in English | WPRIM | ID: wpr-776891

ABSTRACT

This study developed a population pharmacokinetic model for sodium tanshinone IIA sulfonate (STS) in healthy volunteers and coronary heart disease (CHD) patients in order to identify significant covariates for the pharmacokinetics of STS. Blood samples were obtained by intense sampling approach from 10 healthy volunteers and sparse sampling from 25 CHD patients, and a population pharmacokinetic analysis was performed by nonlinear mixed-effect modeling. The final model was evaluated by bootstrap and visual predictive check. A total of 230 plasma concentrations were included, 137 from healthy volunteers and 93 from CHD patients. It was a two-compartment model with first-order elimination. The typical value of the apparent clearance (CL) of STS in CHD patients with total bilirubin (TBIL) level of 10 μmol(L was 48.7 L(h with inter individual variability of 27.4%, whereas that in healthy volunteers with the same TBIL level was 63.1 L(h. Residual variability was described by a proportional error model and estimated at 5.2%. The CL of STS in CHD patients was lower than that in healthy volunteers and decreased when TBIL levels increased. The bootstrap and visual predictive check confirmed the stability and validity of the final model. These results suggested that STS dosage adjustment might be considered based on TBIL levels in CHD patients.


Subject(s)
Adult , Aged , Aged, 80 and over , Bilirubin , Blood , Coronary Disease , Drug Therapy , Metabolism , Drugs, Chinese Herbal , Pharmacokinetics , Female , Humans , Male , Metabolic Clearance Rate , Middle Aged , Models, Biological , Phenanthrenes , Blood , Pharmacokinetics
5.
Acta Pharmaceutica Sinica ; (12): 1318-1323, 2018.
Article in Chinese | WPRIM | ID: wpr-780002

ABSTRACT

Oxcarbazepine (OXC) is a common antiepileptic drugs. In this study, one hundred and eighty four epilepsy patients with 196 observations of oxcarbazepine's active metabolite, 10,11-dihydro-10-monohydroxy carbazepine (MHD) were collected prospectively from routine clinical monitoring. Nonlinear mixed effect modeling was employed to develop a population pharmacokinetic model of oxcarbazepine in Chinese patients with epilepsy to investigate the impact of gender, age, weight, co-medications and genetic polymorphisms of UGT2B7 c.802T>C, ABCC2 c.1249G>A, ABCC 23972C>T on pharmacokinetic characteristics of OXC. The population estimate of apparent clearance (CL/F) and apparent volume of distribution (V/F) was 1.84 L·h−1 and 275 L, respectively. Gender and UGT2B7 c.802T>C affected the clearance rate of MHD significantly. The established model was:CL/F=1.84×0.848UGT2B7×1.17GENDER. Where the genotype of UGT2B7 c.802T>C was CC, UGT2B7=0, otherwise UGT2B7=1. When the patient was male, GENDER=1, otherwise GENDER=0. The final model was evaluated by normalized predictive distribution error (NPDE) and bootstrap method. The model was stable and reliable, which offers a powerful approach for rational use of OXC in epilepsy patients.

6.
Acta Pharmaceutica Sinica ; (12): 263-270, 2018.
Article in Chinese | WPRIM | ID: wpr-779872

ABSTRACT

Tacrolimus is commonly used in the treatment for the refractory primary nephrotic syndrome (PNS) in the pediatric patients. Data were retrospectively obtained from 100 children with 357 tacrolimus trough concentrations in our center between May 2010 and March 2016. Information of age, sex, body weight, drug dose, co-therapy medications, laboratory tests and sampling time were collected. The population pharmacokinetic model was developed using nonlinear mixed effect modeling (NONMEM) software. A one-compartment model with first-order absorption and elimination best described the data. The population estimate of apparent clearance (CL/F) and apparent volume of distribution (V/F) was 6.54 L·h-1 and 86.2 L, respectively. Body weight (WT, kg), daily dose of tacrolimus (DD, mg·day-1) and co-therapy azole antifungal agent have a significant impact on the CL/F. The final PPK model of CL/F was:CL/F=6.54×((WT)/25)K×((DD)/1.5)0.293×0.657Azole,K=(WT-30.9)/(WT-30.9+10.4-30.9). When combined with azole antifungal agents, Azole was 1, whereas vice versa was 0. This is the first PPK study of tacrolimus conducted in pediatric patients with PNS, which may facilitate individualized drug therapy of tacrolimus.

7.
Acta Pharmaceutica Sinica ; (12): 104-110, 2018.
Article in Chinese | WPRIM | ID: wpr-779852

ABSTRACT

Vancomycin has been widely prescribed as the first-line antibiotic in the treatment of methicillin-resistant Staphylococcus aureus and other serious Gram-positive infections. Due to its large pharmacokinetic (PK) variability and narrow therapeutic range, it requires optimization of dosage to achieve target exposure. In this study, SmartDose, a decision support system for individualization of vancomycin dosage is developed using the maximum a posterior Bayesian estimation (MAPB) by the open-source language R combined with the population PK characteristics of vancomycin in Chinese patients. It provides initial design and adjustment of dose regimens based on the therapeutic drug monitoring (TDM) results, as well as a user-defined module to facilitate optimal vancomycin therapy. SmartDose has a high computational reliability, which is validated by NONMEM, the golden standard PK software. Meanwhile, SmartDose is established as a web-based application and its operational flexibility makes it an efficient tool for vancomycin dose optimization in routine clinical settings.

8.
Article in Chinese | WPRIM | ID: wpr-706982

ABSTRACT

Objective To screen TCM dominant diseases from service efficiency, service quality and security by taking a three-A-grade TCM hospital as example.Methods According to the diagnosis related data of the TCM hospital, the common diseases in major disease categories (MDC) were screened out. Average cost of hospitalization, average hospitalization days, antibiotic use rates, blood use rates, and mortality rates were compared with the average level of tertiary general hospitals.Results Totally 27 common diseases were screened out. Three diseases had advantages in terms of service efficiency, security and service quality; 14 diseases had security advantage; 13 diseases had advantage in service quality.Conclusion Compared with three-A-grade general hospitals, most of the common diseases in the hospital has obvious advantages in security and service quality, but the average length of hospitalization in the hospital is longer, and the average cost of most of the common diseases is higher than the general hospital, without advantages in service efficiency.

9.
Article in Chinese | WPRIM | ID: wpr-754620

ABSTRACT

How to use traditional medicine to play the role of primary health care to achieve strategic objectives of universal health coverage and health for all is an important issue for traditional medical development. World Health Organization (WHO) called out that the health system should return to primary health system which was officially launched 30 years ago. "Universal Health Coverage" was list as one of the overall objectives of WHO overall program in 2014-2019. WHO advocated incorporating traditional medicine into primary health care system to promote universal health coverage. At the same time, under the new situation of returning to the "basic health care", China has accumulated rich experience in incorporating TCM into basic health care system. Chinese medicine service has been successfully incorporated into the national basic public health services in grassroots medical institutions, and Chinese medicine service capacity has also been significantly improved under the guidance of good policy.

10.
Article in Chinese | WPRIM | ID: wpr-612599

ABSTRACT

Objective To explore the cost-effectiveness and clinical effect of three platinum based chemotherapy regiments for advanced non small cell lung cancer (NSCLC).Methods 100 patients who were diagnosed as NSCLC,were randomly divided into four groups.The group Ⅰ received NP which was given NVB and DDP.The group Ⅱreceived GP which was given GEM and DDP.The group Ⅲ received TP which was given taxotere and DDP.The clinical effect,adverse reaction and cost effectiveness of the three groups were assessed.Results The clinical effective rates of the three groups were 31.43%,36.36%,37.50% from Ⅰ to Ⅲ group.The adverse events of the group Ⅰ and group Ⅱ were more than those of the group Ⅲ.In the adverse effects of treatment,the major cytotoxicity was digestive reaction and leukopenia in the two groups,but they were tolerable.The ratios of cost effectiveness in the four groups were 550.22yuan,556.48yuan,583.23yuan from Ⅰ to Ⅲ group.Conclusion The NP group is the best one in total cost.

11.
Article in Chinese | WPRIM | ID: wpr-667490

ABSTRACT

Objective To investigate the pathogen distribution and drug resistance condition in patients after lung transplantation so as to guide the reasonable use of antibiotics.Methods The clinical specimens from 242 lung transplantation patients in Wuxi People's Hospital between Jan.2010 to Dec.2016 were retrospectively analyzed.Among the 242 patients,182 were males and 60 were females with the average age of (52 ± 15) years old.Automatic analysis instrument VITEK-2 was applied for pathogen detection and K-B method was used to test drug resistance.Results From 2373specimens,1005 strains of pathogens were isolated and the detection rate was 42.35% (1005/2373),in which gram-negative bacteria accounted for 81.79% (822/1005).The specimens mainly resulted from sputum (76.19 %) and bronchoalveolar lavage (19.76 %).Among those strains,acinetobacter baumannii (28.76%),pseudomonas aeruginosa (16.62%),klebsiella pneumonia (14.33%),escherichia coli (5.57%) and Stenotrophomonas maltophilia (4.88%) ranked the top five species.Acinetobacter baumannii strains were highly resistant to most of antibiotic agents,with the drug resistant rate from 59.52% to 100%,except cefperazone-sulbactam (< 50%).Pseudomonas aeruginosa strains were highly resistant to cefazolin,ceftriaxone,cefotetan,ampicillin,ampicillinsulbactam with the resistance rate of 80.24%-98.80%,while compared to other anibiotics with the resistance rate less than 50%.Stenotrophomonas maltophilia strains with intrinsic drug resistance to imipenem were sensitive to trimethoprim-sulfamethoxazole,cefperazone-sulbactam,piperacillintazobactam,levofloxacin,ciprofloxacin with the drug resistance rate of 12.24%,14.29%,32.65%,16.33% and 18.37% respectively.Klebsiella Klebsiella pneumoniae and escherichia coli,whose resistant rate to ceftazidime,cefperazone-sulbactam,piperacillin-tazobactam,aztreonam,amikacin and tobramycin was all less than 50%,were highly sensitive to imipenem,with the resistance rate of 24.31% and 7.14% respectively.Gram-positive bacteria were accounted for 9.35%,mainly Staphylococcus aureus,Staphylococcus haemolyticus and Staphylococcus epidemics,and drug resistant rate of them to vancomycin was all less than 20.00%.Fungi were accounted for 8.86%,mainly Candida albicans and Filamentous fungi,whose drug resistance rate to 5 antifungal drugs was less than 20.00%.The drug resistance rate of C.glabrata strains and C.krusei strains to fluconazole was 80.00% and 100.00%,respectively.Conclusion The incidence of gram-negative bacteria infection and multiple bacterial strain infection in patients after lung transplantation is very high and the nonfermentation bacteria are highly resistant to multiple antibiotics.So,the rational antibiotics' use inclinical practice should be based on drug sensitivity results in order to improve the lung transplant recipients' survival rate.

12.
Article in Chinese | WPRIM | ID: wpr-511718

ABSTRACT

Background: Previous study has found that ursolic acid (UA) inhibited the proliferation of gastric cancer cells by the down-regulation of cyclooxygenase-2 (COX-2) expression.However,its molecular mechanism is not fully clear.Aims: To investigate the role of adenosine monophosphate-activated protein kinase (AMPK)/signal transducer and activator of transcription 3 (STAT3)/COX-2 signaling pathway in UA-mediated inhibition of gastric cancer cells proliferation.Methods: AMPK-pLVX,AMPK-shRNA,STAT3-pLVX,STAT3-shRNA plasmids were constructed,and then were transfected into human gastric cancer cell lines SGC-7901 and MKN-45,respectively.Gastric cancer cells were cultured with different concentrations of UA for different times.The expressions of phosphorylated AMPK (p-AMPK),phosphorylated STAT3 (p-STAT3) and COX-2 were measured by Western blotting,and cell proliferation was detected by CCK-8 assay.Results: UA dose-and time-dependently increased p-AMPK expression,inhibited p-STAT3 and COX-2 expressions in SGC-7901 and MKN-45 cells.Knockdown of AMPK blocked UA-induced inhibition of STAT3 phosphorylation and COX-2 expression.Overexpression of STAT3 blocked UA-induced down-regulation of COX-2 expression.Knockdown of AMPK and overexpression of STAT3 blocked UA-induced inhibition of proliferation of gastric cancer cells.Conclusions: UA may inhibit the proliferation of gastric cancer cells via down-regulation of COX-2 expression through AMPK/STAT3 pathway.

13.
Chinese Pharmacological Bulletin ; (12): 925-931,932, 2016.
Article in Chinese | WPRIM | ID: wpr-604380

ABSTRACT

Aim Our previous study has found that ur-solic acid( UA) increased intracellular reactive oxygen species ( ROS ) production and adenosine monophos-phate-activated protein kinase ( AMPK ) phosphoryla-tion, inhibited signal transducer and activator of tran-scription 3 ( STAT3 ) phosphorylation and cyclooxygen-ase-2 ( COX-2 ) expression in gastric cancer cells . However , the molecular mechanism by which UA in-hibits COX-2 expression in gastric cancer cells has not been fully clarified .In this study we aimed to further clarify the signal transduction pathways involved in the UA-mediated inhibition of COX-2 expression in gastric cancer cells .Methods Human gastric cancer cell lines SGC-7901 and MKN-45 were routinely cultured in RPMI-1640 medium supplemented with 10% heat-in-activated fetal calf serum .Sub-confluent cell cultures were pre-treated with antioxidant N-acetylcysteine ( NAC) , AMPK activator 5-amino-4-imida-zolecarbox-amide-riboside ( AICAR ) , AMPK inhibitor compound C, or STAT3 inhibitor WP1066 and then treated with or without UA for 24 h.The expression of AMPK and phosphorylated AMPK ( p-AMPK ) , STAT3 and phos-phorylated STAT3 ( p-STAT3 ) , as well as COX-2 was detected by Western blot analysis .Results Antioxi-dant NAC and AMPK inhibitor compound C blocked UA-induced inhibition of STAT 3 phosphorylation and down-regulation of COX-2 expression in gastric cancer cells.Both AMPK activator AICAR and UA inhibited STAT3 phosphorylation and COX-2 expression; the combination of two drugs resulted in further reduction . STAT3 inhibitor WP1066 did not affect UA-induced AMPK phosphorylation , whereas it inhibited STAT3 phosphorylation and COX-2 expression .The inhibitory effects on the STAT3 phosphorylation and COX-2 ex-pression were significantly enhanced when SGC-7901 and MKN-45 cells were treated simultaneously with WP1066 plus UA.Conclusion UA inhibits COX-2 expression in gastric cancer cells , which may be medi-ated through ROS/AMPK/STAT3 signal transduction pathway .

14.
Chinese Pharmacological Bulletin ; (12): 868-872,873, 2016.
Article in Chinese | WPRIM | ID: wpr-604223

ABSTRACT

Aim ToobservetheeffectofSanHuang Decoction (SHD )on glucose and lipid metabolism in insulin resistance(IR)3T3-L1 adipocytes.Methods TheIRmodelof3T3-L1adipocyteswasinducedby high glucose and hyperinsulinism cultivation(also con-taining dexamethasone ).The adipocytes were treated with rosiglitazone(Ros)and different concentrations of SHD(2. 5,5,10,20,40 g·L-1 )for 24 h.The content of glucose disappeared from the culture medium was determined as glucose consumption of the cells. The transport of glucose was observed by 2-deoxidation-[3 H]-glucose uptake method.The efflux of nonesteri-fied fatty acids(NEFA)from adipocytes was observed by the concentration of NEFA in the culture medium. The mRNA expression of glucose transporter-4 (GLUT-4)was measured by real-time polymerase chain reac-tion (real-time PCR).The protein expression of GLUT-4wasdetectedbyWesternblot.Results Compared with the Con group,SHD(5,10,20,40 g·L-1 ) could significantly induce the glucose consumption and transportion(P0.05).Conclusion SHDcanin-crease insulin sensitivity by increasing glucose trans-portation and consumption in the 3T3-L1 adipocytes as well as decreasing the NEFA efflux from the cells.

15.
Acta Pharmaceutica Sinica ; (12): 1666-2016.
Article in Chinese | WPRIM | ID: wpr-779356

ABSTRACT

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in de novo biosynthesis of guanine and plays an important role in cell proliferation. In clinic, IMPDH inhibitors are mainly used in fields of anticancer, antiviral, anti-parasitic, and immunosuppressive chemotherapy. However, since there are usually great inter-and intra-individual variability between drug concentration and clinical effect of IMPDH inhibitors, the enzyme activity of IMPDH may be applied as a specific biomarker and combined with the pharmacokinetics (PK) monitoring to improve efficacy and safety of IMPDH inhibitors. This review aims to discuss the assay of IMPDH activity measurement and its clinical application in recent years and provide valuable insights and theoretical basis for the development of IMPDH inhibitors' pharmacodynamics monitoring.

16.
Acta Pharmaceutica Sinica ; (12): 686-694, 2014.
Article in Chinese | WPRIM | ID: wpr-245026

ABSTRACT

The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4. Monte Carlo simulations were performed to produce state-steady trough concentrations. One-compartment model was used to fit simulated data from oxcarbazepine and tacrolimus. The accuracy and precision of the estimated parameters were evaluated using the median prediction error (PE), the median absolute PE and boxplot. The results indicated that trough concentrations could yield reliable estimates of apparent clearance (CL/F). For oxcarbazepine, as the number of trough concentrations per subject increased, the accuracy and precision of CL/F, between-subject variability (BSV) of CL/F and residual variability (RUV) tended to be improved. For tacrolimus, however, although no improvement were observed in the accuracy of CL/F and BSV of CL/F, the PE distribution ranges were significantly narrowed and the RUV estimates were less bias and imprecise. In terms of algorithm, Monte Carlo importance sampling (IMP) and IMP assisted by mode a posteriori estimation (IMPMAP) were consistently better than other methods. Additionally, the sampling design had no significant effects on the individual parameter estimates, which were only depended on the interaction between BSV and RUV in various algorithms. Decreased in BSV and RUV levels can improve the accuracy and precision of the estimation for both population and individual pharmacokinetic parameter estimates.


Subject(s)
Algorithms , Bayes Theorem , Carbamazepine , Pharmacokinetics , Humans , Immunosuppressive Agents , Pharmacokinetics , Models, Biological , Monte Carlo Method , Nonlinear Dynamics , Regression Analysis , Tacrolimus , Pharmacokinetics
17.
Acta Pharmaceutica Sinica ; (12): 686-94, 2014.
Article in Chinese | WPRIM | ID: wpr-448640

ABSTRACT

The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4. Monte Carlo simulations were performed to produce state-steady trough concentrations. One-compartment model was used to fit simulated data from oxcarbazepine and tacrolimus. The accuracy and precision of the estimated parameters were evaluated using the median prediction error (PE), the median absolute PE and boxplot. The results indicated that trough concentrations could yield reliable estimates of apparent clearance (CL/F). For oxcarbazepine, as the number of trough concentrations per subject increased, the accuracy and precision of CL/F, between-subject variability (BSV) of CL/F and residual variability (RUV) tended to be improved. For tacrolimus, however, although no improvement were observed in the accuracy of CL/F and BSV of CL/F, the PE distribution ranges were significantly narrowed and the RUV estimates were less bias and imprecise. In terms of algorithm, Monte Carlo importance sampling (IMP) and IMP assisted by mode a posteriori estimation (IMPMAP) were consistently better than other methods. Additionally, the sampling design had no significant effects on the individual parameter estimates, which were only depended on the interaction between BSV and RUV in various algorithms. Decreased in BSV and RUV levels can improve the accuracy and precision of the estimation for both population and individual pharmacokinetic parameter estimates.

18.
Article in Chinese | WPRIM | ID: wpr-350652

ABSTRACT

Chinese Pharmacopoeia I (2010 edition) covers dosage and usage of traditional Chinese medicinal herbs and decoction pieces, and provides dosage ranges of most of decoction pieces. By using the descriptive statistical method, the article discusses the distribution of maximum dosage, minimum dosage and dosage range of decoction pieces set forth in Chinese Pharmacopoeia, and compares toxic drugs and non-toxic drugs. Altogether 617 drugs are included into the study. Except for 16 decoction pieces whose dosages are not clear, all of the remaining decoction pieces are covered by Chinese Pharmacopoeia, with the maximum common dosage, minimum common dosage and dosage range of 3, 10 and 6 g. Upon comparison, we discovered that Chinese Pharmacopoeia sets stricter standards for toxic drugs than non-toxic drugs. Compared with dosages in classical prescriptions and actual clinical usages, dosage ranges described in Chinese Pharmacopoeia are much narrower. There is no significant difference between drugs that can be used as foods or healthcare foods and other drugs according to Chinese Pharmacopoeia.


Subject(s)
Drug Dosage Calculations , Drug Therapy , Reference Standards , Drugs, Chinese Herbal , Chemistry , Pharmacology , Toxicity , Humans , Prescriptions , Reference Standards
19.
National Journal of Andrology ; (12): 820-825, 2013.
Article in Chinese | WPRIM | ID: wpr-267994

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the regulatory effect of Yijing Fang (YJF) on adenine-induced infertility in rats with kidney deficiency.</p><p><b>METHODS</b>Sixty healthy Wistar male rats, aged 1.5 mo and weighing (180 +/- 10) g, were normally fed for a week, and then divided into five groups of equal number (blank control, infertile model, high-dose YJF, mid-dose YJF, and low-dose YJF) according to the body weight of the rats. The models were made by intragastric administration of 500 mg/ml adenine in gum arabic solution in the ratio of 1:10 at the dose of 1 ml per 100 g body weight per day for 10 days. YJF was given at 3.38 g, 1.69 g and 0.85 g per 100 g body weight per day to the rats in the high-, mid- and low-dose groups, respectively. After 48 days of treatment, we observed kidney deficiency-related changes in sperm concentration and motility, the levels of testosterone (T) and other hormones and the volumes of the testis, epididymis, seminal vesicle and prostate, and compared the indexes among different groups.</p><p><b>RESULTS</b>YJF exhibited a significant regulatory effect on sperm concentration and motility, the T level and the indexes of the gonad and other accessory glands in the model rats (P < 0.05). After 48 days of treatment, sperm concentrations were (87.85 +/- 28.44), (7.11 +/- 2.15), (35.98 +/- 14.04), (32.65 +/- 11.80) and (33.51 +/- 13.26) x 10(6)/ml in the blank control, infertile model, high-dose YJF, mid-dose YJF, and low-dose YJF groups, respectively; sperm motilities were (52.79 +/- 16.43), (31.14 +/- 3.07), (45.88 +/- 16.97), (51.56 +/- 13.35) and (49.53 +/- 10.16)%; the T levels were (194.07 +/- 40.29), (61.27 +/- 13.70), (121.87 +/- 24.35), (127.44 +/- 19.38) and (127.81 +/- 20.28) nmol/L; the luteinizing hormone (LH) levels were (7.017 +/- 0.269), (6.117 +/- 0.894), (7.060 +/- 0.871), (7.156 +/- 0.937) and (6.967 +/- 0.778) IU/L; the testis volumes were (3.775 +/- 0.183), (2.865 +/- 0.258), (3.236 +/- 0.058), (3.457 +/- 0.066) and (3.398 +/- 0.091) g; the epididymis volumes were (1.119 +/- 0.116), (0.833 +/- 0.226), (1.124 +/- 0.104), (1.132 +/- 0.107) and (1.114 +/- 0.106) g; the prostate volumes were (176.75 +/- 427.09), (131.67 +/- 39.45), (178.70 +/- 37.97), (180.11 +/- 37.39) and (179.00 +/- 35.42) mg; and the body weights were (188.50 +/- 7.12), (189.92 +/- 6.67), (187.42 +/- 5.47), (189.17 +/- 6.19) and (188.75 +/- 6.12) g. Testis histopathology showed obvious injuries in the infertile models and different degrees of improvement in the three YJF groups, most evidently in the mid-dose group.</p><p><b>CONCLUSION</b>Yifing Fang had an evident therapeutic effect on kidney deficiency-related infertility in adenine-induced rat models.</p>


Subject(s)
Adenine , Animals , Disease Models, Animal , Drugs, Chinese Herbal , Therapeutic Uses , Infertility, Male , Drug Therapy , Male , Phytotherapy , Rats , Rats, Wistar
20.
Chinese Medical Journal ; (24): 4233-4238, 2012.
Article in English | WPRIM | ID: wpr-339865

ABSTRACT

<p><b>BACKGROUND</b>Cyclosporin A (CsA) is a substrate of both cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), some of the single nucleotide polymorphisms (SNPs) in these genes are associated with interindividual variations in CsA pharmacokinetics. We studied the influence of these SNPs on the incidence of rejection and CsA nephrotoxicity, as well as pneumonia within one year after renal transplant and post-transplantation diabetes mellitus (PTDM), in order to find whether genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.</p><p><b>METHODS</b>A total of 208 renal transplant recipients receiving CsA were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T), CYP3A4 1G, and CYP3A5 3 by direct sequencing method. Retrospective case control study was utilized to identify the association between CYP3A4 1G, CYP3A5 3, ABCB1 genetic polymorphisms and CsA-related outcomes.</p><p><b>RESULTS</b>The patients with a CYP3A4 1G/ 1G genotype were found to have a higher incidence of acute rejection compared with those with CYP3A4 1/1.</p><p><b>CONCLUSION</b>CYP3A4 1G/1G genotype predict increased risk of acute rejection, so genetic evaluation may partly help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.</p>


Subject(s)
ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Genetics , Asian Continental Ancestry Group , Genetics , Case-Control Studies , Cyclosporine , Therapeutic Uses , Cytochrome P-450 CYP3A , Genetics , Genotype , Humans , Immunosuppressive Agents , Therapeutic Uses , Kidney Transplantation , Polymorphism, Genetic , Genetics , Retrospective Studies
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