Effect of Arg188Gln (G/A) mutation on enzymatic activity of kynureninase / 浙江大学学报·医学版

Objective: To verify whether the enzymatic activity of kynureninase (KYNU) could be changed by the Arg188Gln (G/A) mutation. Methods: The total RNA of human hepatic tissue was extracted and the KYNU gene cDNA was amplified by RT-PCR. Primers were designed according to the sequences around the site Arg188Gln of KYNU gene and the Arg188Gln (G/A) mutant KYNU cDNA was generated by site-directed mutagenesis. Both the wild-type and mutant-type KYNU genes were subcloned into pcDNA vectors and the recombinant plasmids were constructed. After being transfected into human embryonic kidney 293 (HEK293) cells, the expression of KYNU recombinant plasmids were assessed by Western blot. The enzymatic activities of KYNU were detected by high performance liquid chromatography (HPLC). Results: The KYNU enzyme activities were expressed in both wild and mutant HEK293 cells. Michaelis constants (Km) of the wild and mutant KYNU were (9.833±0.513) μmol/L and (29.900±0.265) μmol/L, respectively (P-1·min-1 and (0.084±0.003) nmol·mg-1·min-1, respectively (PConclusion: Arg188Gln (G/A) mutation can decrease the enzymatic activity of KYNU.

Efficacy and safety of fixed combination of nitrendipine and atenolol in treatment for patients with mild to moderate essential hypertension and their optimal dosage matching / 中华全科医师杂志

Objective To evaluate efficacy and safety of fixed combination of nitrendipine and atenolol in treatment for patients with mild to moderate essential hypertension and their optimal dosage matching.Methods Totally,275 patients with essential hypertension were selcted from seven hospitals in Shanghai,Nanjing and Suzhou,China and randomized into five groups with same proportional probability in a double-blind,double-dummy,parallel active-controlled,multi-center clinical trial,receiving fixed combination of nitrendipine and atenolol at three different dosage matching (nitrendipine/atenolol 5/12.5 mg,5/10 mg,5/7.5 mg for groups 1,2 and 3),and nitrendipine (10 mg for group 4) or atenolol (25 mg for group 5),respectively for eight weeks.Results Mean reduction of diastolic blood pressure (DBP)was (17±7) mm Hg,(18±9) mm Hg and (17±7) mm Hg for groupl,2 and 3,respectively from the baseline,significantly greater than that in groups 4 and 5[(13±7) mm Hg and (12±6) mm Hg,respectively].Mean reduction of systolic blood pressure (SBP) was (21 ±11)mm Hg,(24±12) mm Hg,(23±11) mm Hg,(19±13) mm Hg and (18±9) mm Hg,respectively for the five groups from the baseline,and the reduction in group 2 was significantly greater than that in group 5,with an overall efficacy of 94.4%,98.1% and 88.2% for groups 1,2 and 3,respectively,all statistically higher than that in group 5 (71.4%) with P＜0.01,eight weeks after treatment.The ratio of patients with increased dose of antihypertensive agents in week 5 was lower in group 2 than that in the other four groups,with mild adverse reaction only,no obvious change in laboratory biochemical examinations,and no needs in special management.Conclusions Fixed combination of atenolol and nitrendipine with an optimal doses of 5 mg and 10 mg respepctively was effective and safe for mild and moderate hypertension with good tolerance.

Association between albuminuria and blood pressure level in patients with essential hypertension / 中华肾脏病杂志

Objective To investigate the association between albuminuria incidence and blood pressure (BP) level or body weight index (BMI) in patients with essential hypertension from five regions in China. Methods A total of 5021 non-diabetic patients with clearly diagnosed essential hypertension were enrolled in our study. The participants came from five cities in China.Urinary albumin/creatinine ratio was measured in these patients for two times. The associations of albuminuria with BP level and BMI were analyzed. Results (1)There was no significant difference of albuminuria incidence between ＜60-year-old and ≥60-year-old patients. The longer the hypertension exited, the higher the albuminuria incidence was. (2) The albuminuria incidence was associated with blood pressure level significantly. The urinary protein excretion increased with the level of blood pressure. The albuminuria incidences in patients with normal BP, upper range of normal BP, Ⅰ , Ⅱ or Ⅲ stage hypertension were 26.3%, 27.3%, 28.7%, 31.5% and 40.3% respectively. (3) The albuminuria incidence was significantly different in patients with uncontrolled BP (≥ 140/90 mm Hg) compared with those with well controlled BP (＜ 140/90 mm Hg) (27.1% vs 30.2%, P＜0.05 ). (4) The albuminuria incidence was higher in obese patients compared with those with normal BMI at same BP level, but the difference was not statistically significant. (5) Patients with albuminuria had more cardiocerebral or renal events as compared to those without proteinuria. Conclusions The albuminuria incidence of non-diabetic hypertensive patients from 5 cities in China is 28.8%, of which the microalbuminuria incidence is 18.6% and the clinical albuminuria incidence is 10.2%. Uncontrolled BP is an important risk factor of proteinuria.

Efficacy and safety of domestic olmesartan in treatment of mild to moderate essential hypertension / 上海交通大学学报（医学版）

Objective To evaluate the efficacy and safety of domestic olmesartan in treatment of mild to moderate essential hypertension in comparison with losartan. Methods Two hundred and thirty-seven patients with mild to moderate essential hypertension were enrolled in a randomized, double-blind, multi-center, paralleded and active-controlled trial, and were divided into olmesartan group (olmesartan 20 mg + losartan 50 mg placebo) and losartan group (losartan 50 mg + olmesartan 20 mg placebo) for a 8-week therapy. Four weeks after treatment, dosages of drugs were doubled in patients with seated diastolic blood pressure ≥90 mmHg (1 mmHg =0.133 kPa). All patients were followed up every two weeks, and the efficacy and adverse effects were observed. Another 32 patients with mild to moderate essential hypertension were enrolled and given olmesartan only, and ambulatory blood pressure monitoring was performed before and 8 weeks after treatment. Results Compared with those before treatment, both systolic blood pressure and diastolic blood pressure significantly decreased in olmesartan group and losartan group 8 weeks after treatment [(15.2 ±13.3) mmHg and (19.5 ±11.8) mmHg, respectively for systolic blood pressure (P <0.001); (15.9 ±7.48) mmHg and (16.2 ± 5.95) mmHg, respectively for diastolic blood pressure (P < 0.01) ], while there was no significant difference between these two groups (P > 0.05). There was no significant difference in total effective rate and incidence of adverse effect between these two groups (86.9% vs 93.7% and 7.63% vs 5.88% , P > 0.05) . Ambulatory blood pressure monitoring demonstrated that trough to peak ratios of systolic blood pressure and diastolic blood pressure were 86% and 71%, respectively. Conclusion Domestic olmesaratan provides an effective, safe and long action in the treatment of mild to moderate essential hypertension.

Left Ventricular Hypertrophy in Patients with Primary Aldosteronism / 中华高血压杂志

Objective To analysis the parameters of left ventricular hypertrophy(LVH) in patients with primary aldosteronism(PA).Methods Two hundred fifty patients were diagnosed as primary aldosteronsim in this study.One hundred fouty two PA patients undergone the adrenal venous sampling(AVS).Adenomas) APA) were diagnosed in 68 patients and idiopathic hyperaldosteronism(IHA) in 74 patients.During the same period, clinical characteristics and cardiovascular events of this group were compared with those of 246 patients with essential hypertension(EHT) randomly matched for age,gender,and systolic and diastolic blood pressure.Echocardiographic examinations and biochemical and hormonal assays were conducted in all subjects.Results 1) Left ventricular end-diastolic dimension(LVEDd) was increased in PA patients compared with values in EHT patients(PA;49.6?4.3 vs EHT:48.3?4.2 mm,P0.05);however,in grade 2 and 3 hypertension,the LVMI in patients with PA was increased compared with values in patients with EHT(P

The Validity of Wrist Blood Pressure Measuring Device (HEM-6000) / 中华高血压杂志

18 years of age were enrolled. The blood pressure measurements at the wrist were compared with the results obtained by auscultatory measurement on left upper arm. Both measurements were taken 3 times in each person. A total 273 measurements were obtained in 91 participants. The evaluation of the accuracy was assessed by 2 statistical methods. (1)The differences between the 2 devices for a given measurement. (2) The differences between the 2 devices for a given person. Results Method 1 showed the sample mean errors and standard deviation of errors were 0.5?7.1 mm Hg for systolic blood pressure(SBP) and -1.6?6.1 mm Hg for diastolic blood pressure(DBP). Method 2 showed they were 0.5?6.1 mm Hg for SBP and -1.6?5.3 mm Hg for DBP. Blood pressure level and the wrist circumferences had no influence on the measurement errors. Conclusion The HEM-6000 wrist blood pressure device apparently met the AAMI criteria and is valid for patient self-measurement.

Effect of Atenolol on the Pharmacokinetics of Nitrendipine in Healthy Volunteers / 中国药房

0.05).CONCLUSION:Single oral dose of atenolol had no significant effect on the pharmacokinetics of nitrendipine.

Linkage analysis of a region on chromosome 2 with essential hypertension in Chinese families / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To verify the linkage of the candidate regions identified in a previous study (markers D2S168, D2S151, D2S142 on chromosome 2) with hypertension in Chinese families.</p><p><b>METHODS</b>A genetic linkage study focused on chromosome 2 was performed on 240 Chinese families containing 856 patients with essential hypertension. A total of 1080 individuals were genotyped using 9 highly polymorphic microsatellite markers around the candidate regions on chromosome 2 with an average spacing of 5 cM. Non-parametric linkage (NPL), parametric linkage analysis and transmission-disequilibrium test (TDT) with the GENEHUNTER software were used to assess evidence for linkage.</p><p><b>RESULTS</b>Linkage of a region on chromosome 2 around D2S151 and D2S142 with hypertension was confirmed by different statistical methods (NPL, LOD score and TDT). However, the linkage of D2S168 could not be replicated in this extension study.</p><p><b>CONCLUSIONS</b>The data suggest that a region on chromosome 2 at or near the loci of D2S142 and D2S151 may harbor genes responsible for the development of essential hypertension in Chinese.</p>

Heritability of serum leptin levels: a twin study / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the contribution of genetic factors to the variance of serum leptin concentration in healthy, normotensive twins.</p><p><b>METHODS</b>A total of 57 pairs of twins were investigated: 28 female and 19 male pairs of monozygotic(MZ) twins, and 6 female and 4 male pairs of dizygotic(DZ) twins. The zygosity of twins was determined by comparing the concordance of the genotype of nine fluorescence-labeled microsatellite markers. The genetic analysis was performed using the variance-based method. Serum leptin levels were determined in duplicate by a radioimmunoassay Kit (Linco Research, Inc., St. Charles, Missouri) as previously described.</p><p><b>RESULTS</b>The test of genetic variance revealed a significantly larger within-pair variance of serum leptin in the DZ twins, in comparison with the MZ twins. The corresponding heritability for serum leptin was 8%. Adjusted for BMI, gender, and uric acid (UA), the heritability for serum leptin was 0.18%. Log leptin correlated significantly with blood pressure (SBp r=0.355 P<0.001; DBp r=0.339 P<0.001). Stepwise multiple linear regression analysis revealed that only BMI, gender and UA were linked independently to serum leptin levels(R(2)=0.788, P<0.001).</p><p><b>CONCLUSION</b>The above data indicate that environmental factors other than genetic factors are important determinants of leptinemia in normal subjects.</p>

Linkage analysis of cytokine and cytokine-related receptor gene loci and essential hypertension in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the genetic linkage between several cytokine and cytokine-related receptor gene loci and essential hypertension (EH) in Chinese.</p><p><b>METHODS</b>Linkage between seven genetic markers and EH in 95 Chinese nuclear families with EH (including 477 subjects) was analyzed using a technique of fluorescence-based gene scan with DNA short tandem repeat loci. These markers were selected from the chromosomal regions nearby eight cytokines and their receptor genes. The two-point non-parametric linkage analysis (NPL), maximum Lod score and transmission/disequilibrium test (TDT) with GENEHUNTER software package were used in this study.</p><p><b>RESULTS</b>Result of TDT showed significant transmission disequilibrium between D14S61 and EH (Chi square 14.29,P=0.00016) although NPL and Lod score revealed no significant linkage (Z=0.78, P>0.05 and Lod score =0.72 respectively) at this locus. No linkage between other loci typed and EH was found by the three genetic analysis methods (P>0.05 or Lod score<-1).</p><p><b>CONCLUSION</b>Alleles at D14S61 were of significant transmission disequilibrium in affected siblings. Transforming growth factor beta 3 is 0.1 cM away from D14S61, which suggests that the relationship between genes at or near this regions and EH needs to be further explored.</p>

Collagen Distribution and its Quantitative Variation in the Aortic Adventitia of Spontaneously Hypertensive Rats / 中华高血压杂志

Objective: To study collagen distribution and its quantitative variation in t he aortic adventitia of spontaneously hypertensive rats Methods: Sirus red stain was used to observe collagen distribution in aortic adventitia；Chloramine-T oxidation assay was employed to quantitate the collagen of aortic adventitia；Immuno-histochemical staining was adopted to detect type Ⅰ、Ⅲ collagen synthetic characteristic of vascular adventitial fibroblasts. Results: Collagen of rat aoritc wall mainly distributes in adventitia；SHR shows more collagen deposition in adventitia than WKY at the age of 8weeks and 24 weeks；The immuno-histochemical staining of type Ⅰ、Ⅲ collagen in vascular a dventitial fibroblasts is positive. Conclusions: All those results indicate that vascular adventitia ma y be involved in hypertensive vascular remodeling.and vascular adventitial fibroblasts can synthe size collagen type Ⅰ and Ⅲ.

Angiotensin Ⅱ and its Antagonists on Cultured Cardiac M yocytes Hypertrophy / 中华高血压杂志

Aim To investigate the effects of angiotensin Ⅱ(AngⅡ),AT1 receptor antagonist losartan and AT2 receptor antagonist PD123177 on protein synthesis rate and AT1 receptor mRNA expression in cultured neonatal rat cardi ac myocytes. 　Methods The protein synthesis rate in cultured cardiac myocytes w as determined by the3H-leucine incorporation,AT1 receptor mRNA expressi on of cardiac myocytes was assessed by reverse transcription-polymerase chain reaction(RT-PCR). 　Results AngⅡ increased the 　3H-leucine incorporation in cultured cardiac myocytes in a dose dependent manner,losartan but not PD12317 7 could significantly inhibit AngⅡ induced protein synthesis,;AT1 receptor mRNA expression was upregulated after AngⅡ,and inhibited by losartan,but not PD123177. 　Conclusion AngⅡ can induce cardiac myocytes hypertrophy via upregulating AT1 receptor,and AT1 receptor antagonist can decrease AT1 rec eptor expression,reduce cardiac myocytes hypertrophy.

Association of single nucleotide polymorphisms of glucagon gene and essential hypertension in Shanghai Chinese / 中华内分泌代谢杂志

Objective To detect and genotype the single-nucleotide polymorphisms (SNPs) in coding and promoter regions of human glucagon gene in Han Chinese residing in Shanghai and to analyse its association with essential hypertension (EH). Methods The identification of SNPs was performed by both direct DNA sequencing and denaturing high-performance liquid chromatography (DHPLC). For genotyping of SNPs direct sequencing was performed in 96 patients with EH and 96 normotensive controls (NT). Results Two SNPs in glucagon gene, one in the coding region (C3689T) and the other in the joint region, (G5505A) were found. A higher frequency SNP, C3689T, was genotyped and no significant difference in C3689T genotype frequency was found between EH and NT. Conclusion There is an important ethnic difference in SNP distribution of human glucagon gene. The distribution of C3689T genotype in Han Chinese is not different between EH and NT.

Role of angiotensin Ⅱ on type Ⅰcollagen synthesis and its mRNA expression in vascular adventitial fibroblasts / 中国病理生理杂志

AIM:Effects of anatotensin Ⅱ on type Ⅰ collagen synthesis and its mRNA expansion in cultured vascular adventitial fibroblasts. METHODS: Vascular adventitial fibroblasts (VAF)were isolated, cultured from rat thoracic aorta by explant method. ELISA was used to study type Ⅰ collagen synthesis and competihve RT - PCR was employed to detect its mRNA expression after angiotensin Ⅱ administration. RESULTS: Angiontensin Ⅱ caused a dose dependent increase of type Ⅰ collagen synthesis and its mRN expression in VAF. CONCLUSION: The results support that angiotensin Ⅱ is an important factor controlling collagen metabolism of VAF and VAF may play an im- portant role in vascular remodelling of hypertension.