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1.
Chinese Journal of School Health ; (12): 1497-1500, 2023.
Article in Chinese | WPRIM | ID: wpr-997211

ABSTRACT

Objective@#To examine the prevalence and factors influencing the inconsistency for knowledge and behavior in condom use among college students, so as to provide suggestions for AIDS prevention and education in universities.@*Methods@#From October to December 2019, a multistage cluster sampling method was employed to collect data relating to inconsistency for knowledge and behavior in condom use and other related factors among 1 303 students from six colleges in Zhuhai, China. Chi square test and Logistic regression were performed to analyze the influencing factors and moderating effect.@*Results@#The reporting rate of in consistency of knowledge and behavior in condom use among college students was 41.1%. Multivariate Logistic regression analysis showed that seeking sexual partners offline was negatively correlated with inconsistency for knowledge and behavior in condom use ( OR=0.70, 95%CI =0.51-0.95). However, condom nonuse during the first sexual experience (OR=7.11, 95%CI=5.23-9.67), smoking before sex ( OR=1.47, 95%CI =1.07-2.02), drinking before sex ( OR=1.44, 95%CI =1.09-1.91), history of intimate partner violence ( OR=1.53, 95%CI =1.13-2.07), and having multiple sexual partners ( OR=1.69, 95%CI =1.25-2.29) were positively correlated with inconsistency for knowledge and behavior in condom use ( P <0.05). The moderating effect analysis showed that condom use during the first sexual experience had a moderating effect on smoking before sex and inconsistency for knowledge and behavior in condom use ( β=0.92, P <0.05). Among students who did not use condoms during the first sexual experience, a positive correlation was observed between smoking before sex and inconsistency for knowledge and behavior in condom use ( OR= 2.76 , 95%CI=1.09-6.99, P <0.05). However, no correlation was found between smoking before sex and inconsistency for knowledge and behavior in condom use ( OR=1.32, 95%CI=0.92-1.88, P >0.05) among students who used condoms during the first sexual experience.@*Conclusion@#High levels of inconsistency for knowledge and behavior in condom use are found among college students in Zhuhai City. Colleges should carry out sex education activities as soon as possible, and explore new health education models to promote the transformation of their knowledge into behavior.

2.
Acta Pharmaceutica Sinica B ; (6): 1514-1522, 2022.
Article in English | WPRIM | ID: wpr-929371

ABSTRACT

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

3.
Neuroscience Bulletin ; (6): 561-580, 2019.
Article in English | WPRIM | ID: wpr-775436

ABSTRACT

Antipsychotic-induced weight gain (AIWG) is a common adverse effect of this treatment, particularly with second-generation antipsychotics, and it is a major health problem around the world. We aimed to review the progress of pharmacogenetic studies on AIWG in the Chinese population to compare the results for Chinese with other ethnic populations, identify the limitations and problems of current studies, and provide future research directions in China. Both English and Chinese electronic databases were searched to identify eligible studies. We determined that > 25 single-nucleotide polymorphisms in 19 genes have been investigated in association with AIWG in Chinese patients over the past few decades. HTR2C rs3813929 is the most frequently studied single-nucleotide polymorphism, and it seems to be the most strongly associated with AIWG in the Chinese population. However, many genes that have been reported to be associated with AIWG in other ethnic populations have not been included in Chinese studies. To explain the pharmacogenetic reasons for AIWG in the Chinese population, genome-wide association studies and multiple-center, standard, unified, and large samples are needed.


Subject(s)
Humans , Antipsychotic Agents , Asian People , Genetics , China , Genome-Wide Association Study , Genotype , Lipid Metabolism , Genetics , Neurosecretory Systems , Pharmacogenomic Testing , Polymorphism, Single Nucleotide , Receptors, Adrenergic , Genetics , Receptors, Dopamine , Genetics , Receptors, Histamine , Genetics , Receptors, Serotonin , Genetics , Weight Gain , Genetics
4.
Journal of Central South University(Medical Sciences) ; (12): 1204-1211, 2017.
Article in Chinese | WPRIM | ID: wpr-669231

ABSTRACT

Translation control in eukaryotes contributes significantly to gene expression regulation during cellular processes,which enables rapid changes of specific proteins to maintain cellular homeostasis.Eukaryotic translation is a multiple-step process that comprised of four phases:initiation,elongation,termination and ribosome recycling.The initiation phase is rate-limiting and orchestrated by a set of eukaryotic translation initiation factors (eIFs).Defects in translation initiation can result in a series of diseases.Among all eIFs,eIF3 is the largest and less-known initiation factor due to its intrinsic complexity.Aberration in eIF3A,the largest subunit of eIF3,is known to contribute to carcinogenesis and protection against evolution into higher-grade malignancy,and the altered expression or mutation of eIF3A affects the responses of cancer patients to platinum-based chemotherapy.Besides its role in cancinogenesis,eIF3A is also implicated in fibrosis,and the agents inhibiting eIF3A delay the progression of this disorder.The dual roles of eIF3A in tumorigenesis are probably due to the regulation of translation of different mRNAs at different stages of tumor progression by eIF3A.In tum the encoded products serve as pro-tumor or anti-tumor proteins at different stages.

5.
Journal of Central South University(Medical Sciences) ; (12): 955-959, 2015.
Article in Chinese | WPRIM | ID: wpr-815243

ABSTRACT

OBJECTIVE@#To investigate the neuroprotective effects of osthole (OST) on glutamate-induced toxicity in hippocampal HT22 cells and to explore the correlation between the protection and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway.
@*METHODS@#The cell injury model of HT22 was induced by glutamate and the cell viability was detected by MTS assay. The lactate dehydrogenase (LDH) release and the caspase-3 activity were determined by commercial kits. Western blot analysis was utilized to detect the protein levels of PI3K, Akt, p-PI3K and p-Akt. 
@*RESULTS@#OST markedly improved the cell survival and decreased the LDH release in glutamate-treated HT22 cells in a dose-dependent manner. Furthermore, the levels of p-PI3K and p-Akt proteins were significantly increased in glutamate and OST-co-treated HT22 cells. The effect of OST on p-Akt phosphorylation in HT22 cells was attenuated in the presence of PI3K specific inhibitor (LY294002).
@*CONCLUSION@#OST protects HT22 cells from glutamate excitotoxicity through a mechanism involving the activation of PI3K/Akt signaling pathway.


Subject(s)
Animals , Mice , Caspase 3 , Metabolism , Cell Line , Cell Survival , Chromones , Pharmacology , Coumarins , Pharmacology , Glutamic Acid , Hippocampus , Cell Biology , Morpholines , Pharmacology , Neuroprotective Agents , Pharmacology , Phosphatidylinositol 3-Kinases , Metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt , Metabolism , Signal Transduction
6.
Chinese Pharmacological Bulletin ; (12): 1211-1215, 2015.
Article in Chinese | WPRIM | ID: wpr-481743

ABSTRACT

Aim To assess the protective role of chry-sophanol in rats with diabetes-associated cognitive de-cline (DACD) and explore the potential molecular mechanisms.Methods The learning and memory performance was assessed by Morris water maze test;the activities of AChE,ChAT,iNOS and oxidative stress markers including CAT,SOD and GSH-PX in the hippocampus were detected using respective com-mercial kits.The level of BDNF was also measured with commercial ELISA kit.Results Chrysophanol significantly improved learning and memory functions in the diabetic groups.Additionally,the activities of AChE,BDNF also found to be evidently increased, while decreased activities of ChAT,iNOS,CAT,SOD and GSH-PX were observed in the hippocampus of dia-betic rats.Conclusions Collectively,chrysophanol has a protective role against DACD and this neuropro-tection is associated with increasing BDNF level.Chry-sophanol can also suppress the activities of iNOS, CAT,SOD and GSH-PX in diabetic rats.It is likely to be a novel therapeutic drug for the treatment of diabetic patients with cognitive deficits in clinical practice.

7.
Journal of Central South University(Medical Sciences) ; (12): 790-796, 2014.
Article in Chinese | WPRIM | ID: wpr-815527

ABSTRACT

OBJECTIVE@#To explore the association of catechol-O-methyltransferase (COMT) Val 108/158 Met polymorphism with essential hypertension in Chinese population.@*METHODS@#COMT Val 108/158 Met polymorphism was detected by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) in a case-control study, including 215 hypertensive patients (hypertensive group, n=215) and 227 controls (control group, n=227).@*RESULTS@#1)There was no significant difference in the frequency distribution of genotypic (Val/Val, Val/Met, and Met/Met) and the allelic of COMT gene Val 108/158 Met polymorphism between the 2 groups (P>0.05). 2) After gender stratification, there was no significant difference in the genotypic and allelic frequency distribution in men or women between the 2 groups (P>0.05). 3) After risk stratification of hypertension, there was no significant difference in the genotypic and allelic frequency distribution between the low risk, middle risk, high risk and very high risk grades (P>0.05). 4) Raised body mass index, blood glucose and low-density lipoprotein, and hypertension family history were risk factors for hypertension by logistic regression analysis, while genotype had no effect on the occurrence of hypertension.@*CONCLUSION@#No relationship between COMT Val 108/158 Met polymorphism and essential hypertension has been found.


Subject(s)
Female , Humans , Male , Alleles , Asian People , Case-Control Studies , Catechol O-Methyltransferase , Genetics , Essential Hypertension , Gene Frequency , Genotype , Hypertension , Genetics , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Risk Factors
8.
Journal of Central South University(Medical Sciences) ; (12): 433-441, 2014.
Article in English | WPRIM | ID: wpr-815418

ABSTRACT

OBJECTIVE@#To investigate whether single nucleotide polymorphisms (SNPs) of rs2298771 and rs3812718 of the sodium channel α-subunit type 1 (SCN1A) gene affect the efficacy of carbamazepine (CBZ) treatment for seizures in Chinese Han epileptic patients.@*METHODS@#SNP rs2298771 and rs3812718 of the SCN1A gene from 628 patients were genotyped. CBZ monotherapy was administered to the subjects with new-onset partial seizures. The efficacy was defined as the decrease in the number of seizures. Four semi-quantitative levels were used to assess the efficacy: seizure-free (SF), >75% seizure decrease (SD), 50%-75% SD, and <50% SD in the number of seizures compared with patients' initial conditions.@*RESULTS@#After the 12 month treatment with CBZ monotherapy, the rate of SF patients with G allele of the SNP rs2298771 was significantly lower than that in patients with the AA genotype (P=0.003). The heterozygote and homozygote of the G allele at SNP rs2298771 predicted the low SF rate (OR=2.101, 95% CI 1.289-3.425). Marginal significance was observed between the dichotomous efficacy of SF and non-SF in 3 partial seizure types (P=0.028).@*CONCLUSION@#rs2298771 is significantly associated with the efficacy of CBZ monotherapy in Chinese Han epileptic patients.


Subject(s)
Humans , Alleles , Asian People , Carbamazepine , Therapeutic Uses , Epilepsy , Genotype , Genetics , Polymorphism, Single Nucleotide , Seizures , Drug Therapy , Genetics
9.
Chinese Pharmacological Bulletin ; (12): 445-447,448, 2014.
Article in Chinese | WPRIM | ID: wpr-598959

ABSTRACT

Translation is a fundamental step in regulation of gene expression and abnormalities in this process may lead to cancer. In eukaryotic cells, translation of mRNA is mainly regulated by many eukaryotic initiation factors ( eIFs) . EIF3 plays an impor-tant role in translational regulation, cell growth and oncogenesis. The largest subunit of eIF3, eIF3a may play a role as a regulator of mRNAs. The relationship between eIF3a and oncogenesis has been found. Moreover, the eIF3a mRNA is ubiquitously ex-pressed in different cancer cells and can modulate the cell cycle. However, some studies indicate that eIF3a could provide protec-tion against evolution into higher malignancy and reduce the re-sistance to chemotherapy . The patients of high eIF3a expression could get a better prognosis . In fact, the role of eIF3a is still un-clear in cancer cells. EIF3a may be involved in the process of tumor pathophysiology, but its regulatory role is undulatory.

10.
Journal of Central South University(Medical Sciences) ; (12): 95-100, 2013.
Article in English | WPRIM | ID: wpr-814919

ABSTRACT

Obesity is a great risk factor for type 2 diabetes and certain types of cancer, which become a major burden for public health worldwide. As a classic complex disease, obesity is regarded as the interaction of genetic and environmental factors. However, it is controversial which of these two factors have greater effect on obesity. Several genetic loci have recently been reported to contribute to the development of obesity reported in genome-wide association study (GWAS) these years. GWAS play an important role in complex disease research and explore the potential effect of genetic variance. To further understand the genetic influence on obesity risk, we reviewed and collected articles on Pubmed for genes that reported in recent GWAS. We summarized the publications in GWAS and found 49 candidate genes, which were strongly suggested to relate to obesity risk in human. Despite the findings of this and other similar, contemporary research projects, much of the single nucleotide polymorphism details and underlying mechanism in this field of study remains, to a great extent, unknown. As a result, future studies are needed for obesity risk in human beings.


Subject(s)
Humans , Aldose-Ketose Isomerases , Genetics , Alpha-Ketoglutarate-Dependent Dioxygenase FTO , Brain-Derived Neurotrophic Factor , Genetics , Genome-Wide Association Study , Obesity , Genetics , Polymorphism, Single Nucleotide , Proteins , Genetics
11.
Journal of Central South University(Medical Sciences) ; (12): 313-317, 2013.
Article in Chinese | WPRIM | ID: wpr-814883

ABSTRACT

Warfarin resistance is a phenomenon that patients need to take much higher than normally prescribed dosage of warfarin to maintain the target therapeutic international normalized ratio (INR) range, or even fail to reach the target INR. Warfarin resistance can be categorized in etiologic terms as hereditary vs acquired, or in pharmacologic terms as pharmacokinetic vs pharmacodynamic. Once warfarin resistance is diagnosed, the type of resistance should be determined as soon as possible so that treatment could be oriented toward the causes. Poor compliance, genetic mutations, concurrent medications that could decrease the absorption or increase the clearance of warfarin, and consumption of diet rich in vitamin K are the major reasons for warfarin resistance. Educating patients, increasing warfarin dosage and switching to other anticoagulants would be effective for warfarin resistance.


Subject(s)
Female , Humans , Male , Anticoagulants , Pharmacology , Drug Monitoring , Methods , International Normalized Ratio , Metabolism, Inborn Errors , Diagnosis , Genetics , Vitamin K , Vitamin K Epoxide Reductases , Genetics
12.
Journal of Central South University(Medical Sciences) ; (12): 949-957, 2011.
Article in Chinese | WPRIM | ID: wpr-669500

ABSTRACT

Objective To explore the association between rs3758539G-803A and rs10882283 T-179G polymorphism of retinol binding protein 4 (RBP4) and rosiglitazone response in Chinese type 2 diabetes mellitus (T2DM) patients.Methods A total of 472 Chinese T2DM patients and 198 healthy subjects were enrolled to identify G-803A and T-179G genotypes using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP ).assay.Forty-two T2DM patients with different G-803A or T-179G genotypes were selected to undergo a 12-week rosiglitazone treatment (4 mg/d).Serum fasting plasma glucose (FPG),postprandial plasma glucose (PPG),fasting serum insulin (FINS),glycated hemoglobin (HbAlc),postprandial serum insulin ( PINS),triglyceride (TG),low-density lipoprotein-cholesterol ( LDL-c),and high-density lipoprotein-cholesterol (HDL-c) were determined before and after the rosiglitazone treatment.Results T2DM patients with RBP4 G-803A GG genotype showed lower TG and LDL-c concentrations compared with that in the GA +AA genotype subjects.T2DM patients with RBP4 T-179G TT genotype showed lower waist-to-hip ratio (WHR),FPG and FINS values compared with that in the TG + GG genotype individuals.Patients with GG genotype of RBP4 G-803A had an enhanced rosiglitazone efficacy on FPG and FINS compared with that in the GA + AA genotype group.Patients with RBP4 T179G TG + GG genotype showed an enhanced rosiglitazone efficacy on HbAlc level compared with that in the TT genotype group.Conclusion RBP4 G-803A and T-179G polymorphism might be associated with the development of T2DM and affect the therapeutic efficacy of rosignitazone in Chinese T2DM patients.

13.
Journal of Central South University(Medical Sciences) ; (12): 958-963, 2011.
Article in Chinese | WPRIM | ID: wpr-669498

ABSTRACT

Objective To investigate the effect of nicotinamide mononucleotide (NMN) on insulin secretion and gene expressions of pancreatic and duodenal homeobox 1 ( PDX-1 ) and forkhead box-containing protein O-1 ( FoxO1 ),which were important transcription factors for insulin secretion.Methods Insulin secretion level in RIN-m5f cells was detected by rat insulin ELISA detection kit.The mRNA expression levels of PDX-1 and FoxO1 in RIN-m5f cells were analyzed by real-time PCR.The protein expression of PDX-1 was measured by Western blot.Results Insulin secretion levels in RIN-m5f cells treated with repaglinide ( 10 nmol/L) plus NMN ( 100 μnol/L) was significantly higher than those in the blank control,the DMSO control group,and the NMN (50μmol/L) treated group (P <0.05 ).The mRNA expression levels of PDX-1 in RIN-m5f cells treated with NMN ( 10,50 and 100 μmol/L) for 36 h were significantly higher than those in the control group (P <0.05,P < 0.01,and P < 0.001,respectively).There was marked differences in the mRNA expression levels of PDX-1 among different concentrations of NMN (P <0.001 ),but no significant differences in the mRNA expression level of FoxO1 ( P > 0.05).No significant difference was found in the protein expression levels of PDX-1 in RIN-m5f cells treated by NMN (50,100,and 200 μmol/L) for 36 or 48 h compared with the control group (P > 0.05).Conclusion NMN can stimulate insulin secretion and upregulate the mRNA expression of PDX-1 in RIN-m5f cells.

14.
Chinese Journal of Endocrinology and Metabolism ; (12): 432-436, 2010.
Article in Chinese | WPRIM | ID: wpr-389731

ABSTRACT

Genome-wide association studies ( CWAS) use high-throughout genotyping technologies to investigate the relation of hundreds of thousands of gene markers(genotype) with clinical conditions and measurable traits (phenotype). Type 2 diabetes mellitus results from the interaction of environmental factors with genetic variants. Many progresses have been acquired from GWAS. New gene regions have been discovered to be involved in the development and function of islet (3-cells, which provides new strategies for the etiology investigation, prevention, and treatment of type 2 diabetes mellitus.

15.
Journal of Central South University(Medical Sciences) ; (12): 1-10, 2010.
Article in Chinese | WPRIM | ID: wpr-404334

ABSTRACT

Objective To explore the distribution pattern of G protein-coupled receptor family C, group 6, subtype A (GPRC6A) mRNA in adult mice. Methods The distribution of GPRC6A mRNA in paraffin embedded adult mouse tissues was determined by highly sensitive nonradioactive cRNA probe in situ hybridization (ISH). We compared ISH with and without addition of tyramide signal amplification (TSA). GPRC6A wild-type and littermate GPRC6A null mice tissue sections were investigated by ISH. Results TSA greatly increased the sensitivity of ISH to detect GPRC6A mRNA in wild type mouse tissues. There was no detection of GPRC6A mRNA in GPRC6A gene specific knockout tissue in paraffin embedded tissue section. The mRNA of GPRC6A was detectable in the digestive gland or accessory digestive gland including salivary gland and pancreas, as well as in the tissues including kidney, testis, brain, muscle, and fat. Conclusion The mRNA distribution pattern of GPRC6A gene is compatible with the phenotype of GPRC6A knockout mice.

16.
Journal of Central South University(Medical Sciences) ; (12): 771-776, 2010.
Article in Chinese | WPRIM | ID: wpr-402305

ABSTRACT

Objective To explore the dose-dependent and time-dependent effect of docetaxel on the expression of mammalian eukaryotic initiation factor 3 subunit A (eIF3a) in lung cancer cell line. Methods The human lung cancer cell line A549 was treated with gradient concentrations of docetaxel for different time. Real-time PCR and Western blot were used to detect mRNA and protein expression levels of eIF3a and α-tubulin, respectively. Results Docetaxel did not affect α-tubulin expression at either mRNA level or protein level. When A549 cells were treated with high concentration of docetaxel (30 μg/L), the expression level of eIF3a mRNA tended to increase in a time-dependent manner. Protein expression level of α-tubulin was not associated with eIF3a expression significantly in cells treated by docetaxel.Conclusion Docetaxel could slightly increase the expression of eIF3a mRNA, and eIF3a does not regulate the expression of α-tubulin in A549 cells treated by docetaxel.

17.
Journal of Central South University(Medical Sciences) ; (12): 318-322, 2009.
Article in Chinese | WPRIM | ID: wpr-814329

ABSTRACT

OBJECTIVE@#To investigate the change of serum MCP-1 level and CCR2 expression in isolated monocytes in patients with acute coronary syndrome (ACS) and its possible relationship with ACS pathogenesis.@*METHODS@#Thirty ACS patients and 30 healthy controls were enrolled. Serum MCP-1 levels were determined by ELISA in all subjects. The protein expression of CCR2 in isolated monocytes was assessed by flow cytometry.@*RESULTS@#Serum MCP-1 concentrations in ACS patients were higher than those in healthy controls (P<0.05) and the ratio of CCR2 protein expression in monocytes in ACS patients was higher than that in healthy controls (P<0.01).@*CONCLUSION@#The serum MCP-1 concentrations and protein expression of CCR2 in ACS patients are significantly higher than those in healthy controls, which might be associated with the pathogenesis of ACS.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Acute Coronary Syndrome , Blood , Case-Control Studies , Chemokine CCL2 , Blood , Monocytes , Metabolism , Receptors, CCR2 , Blood
18.
Journal of Central South University(Medical Sciences) ; (12): 359-367, 2007.
Article in Chinese | WPRIM | ID: wpr-407935

ABSTRACT

The prevalent rates of overweight and obesity are steadily increasing all over the world. Previous studies of some candidate genes have indicated that most of the genes are associated with obesity in human adipose tissue. As much as 40% of the variations in body mass could be attributed to genetic difference. The β-adrenergic receptor (β-AR) plays a major role in the regulation of energy balance in humans. A high sympathetic nervous system activity has been shown to be associated with obesity and is believed to have pathogenetic relevance. Several common single nucleotide polymorphisms (SNPs) including Gly389Arg in β1-AR, Gln27Glu in β2-AR, and Trp64Arg in β3-AR in humans could alter receptor function and these variations ofβ-ARs were shown to have certain association with obesity. Here we summarize the genetic polymorphisms of human β-ARs and their potential impacts to obesity.

19.
Chinese Journal of Clinical Pharmacology and Therapeutics ; (12): 1130-1137, 2007.
Article in Chinese | WPRIM | ID: wpr-407641

ABSTRACT

BACKGROUND: Metoprolol is a selective β1-Blocker commonly used in essential hypertension. It is metabolized by CYP2D6. CYP2D6*10, which was identified to decrease activity of CYP2D6, is the main variance in Chinese population. β1-adrenergic receptor, with Ser49Gly and Gly389Arg polymorphisms, is the target of metoprolol. It was still unknown that whether the CYP2D6 and β1-adrenergic receptor had a synergic effect on metoprolol antihypertension therapy. AIM: To clarify the genetic polymorphism associated with metoprolol pharmacokinetics and pharmacodynamics in antihypertension therapy. METHODS: 125 mild-to-med essential hypertension patients were enrolled in this study. Patients were mono-therapied with metoprolol for 12 weeks. Blood pressure was monitored every 4 weeks. PCR-RFLP method was use to identify CYP2D6*10 and β1-adrenergic receptor Ser49Gly and Gly389Arg polymorphisms. Plasma metoprolol concentration was measured by HPLC- fluorescence detection. RESULTS: Trough blood level (C0) of metoprolol was associated with CYP2D6*10 variance in a gene-dose-effect manner, whereas the extent of blood pressure decrease was not significant different in CYP2D6*1*1, *1*10 and CYP2D6*10*10 patients. After 12 weeks metoprolol therapy, Gly49 carriers had stronger decrease in systolic and diastolic blood pressure than that of Ser49 homozygotes. Similarly, subjects homozygous for Arg389 had stronger decrease in blood pressure than that of Gly389 carriers. CONCLUSION: CYP2D6*10 variance significantly change the pharmacokinetics of metoprolol, and the genetic polymorphisms of β1-adrenergic receptor were associated with the pharmacodynamics of metopolol in antihypertension therapy.

20.
Chinese Journal of Clinical Pharmacology and Therapeutics ; (12): 1157-1162, 2007.
Article in Chinese | WPRIM | ID: wpr-407638

ABSTRACT

BACKGROUND: There is a growing recognition that the adipose tissue is an endocrine organ that secretes signaling molecules such as adiponectin and resistin. The peroxisome proliferator activated receptor γ (PPARγ) is expressed in high levels in the adipose tissue. Thiazolidinediones are selective PPARγ agonists with insulin-sensitizing properties. It has been postulated that thiazolidinediones such as rosiglitazone exert their pharmacodynamic effects in part through modulation of resistin (implicated in insulin resistance) and adiponectin (an insulin-sensitizing molecule) expression subsequent to activation of PPARγ. There are conflicting data, however, on the biological direction in which resistin expression is modulated by PPARγ agonists and whether an increase in adiponectin expression can occur in the face of an upregulation of resistin. METHODS: Using the murine 3T3-L1 adipocytes as a model, we evaluated the changes in resistin and adiponectin gene expression after vehicle, rosiglitazone (10 μmol/L, a PPARγ agonist), GW9662 (5 μmol/L, a selective PPARγ antagonist) or GW662 and rosiglitazone co-treatment.RESULTS: In comparison to vehicle treatment, rosiglitazone increased the average adiponectin and resistin mRNA expression by 1.66- and 1.55-fold, respectively (P<0.05). Importantly, GW9662 also upregulated adiponectin expression (by 1.57-fold, P<0.05) but did not influence resistin expression (P>0.05). Co-treatment with rosiglitazone and GW9662 maintained the adiponectin upregulation (1.87-fold increase from vehicle, P<0.05) while attenuating resistin upregulation (1.31-fold increase from vehicle, P<0.05) induced by rosiglitazone alone (1.55-fold increase from vehicle, P<0.05). CONCLUSION: This study presents new evidence that adiponectin transcript is upregulated with both a PPARγ agonist (rosiglitazone) and antagonist (GW9662), while GW9662 co-treatment does not block rosiglitazone-induced adiponectin upregulation. These data collectively suggest that biological mechanisms independent from PPARγ may underlie thiazolidinedione pharmacodynamics on adiponectin expression. Moreover, increased adiponectin expression by GW9662, in the absence of an upregulation of resistin expression, lends further support on the emerging clinical potential of PPARγ antagonists in treatment of insulin resistance. Decreased resistin expression may not be crucial for the insulin-sensitizing effect of rosiglitazone. These findings may serve as a foundation for future dose-ranging and time-course studies of thiazolidinedione pharmacodynamics on adipocytokine expression in human adipocytes.

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