Relationship of blood pressure variability and angiotensinogen T235M polymorphism with Binswanger's disease / 中华老年医学杂志

Objective To detect the relationship of blood pressure variability (BPV) and angiotensinogen(AGT) T235M polymorphism with Binswanger's disease (BD).Methods Totally 122 cases with BD and 108 cases with essential hypertension had been enrolled.Ambulatory blood pressure monitoring was used to get the data of BPV and mean blood pressure (MBP).PCR-RFLP was applied to detect genotype of AGT T235M.Results Distribution of MM+MT genotype and frequency of M allelic were higher in BD group (51.6％,29.9％) than in hypertension group(27.8％,16.2％)(x2 ＝13.543,11.995,P＜0.01).The variability of night time blood pressure (11.8±2.8,9.1±2.5) and 24 hours diastolic blood pressure(11.6±6.0) in BD group were increased compared with those in hypertension groups(10.9±2.4,8.2±3.2,10.1±4.6)(t＝2.59,2.64,2.09,all P＜0.05).Prevalence of anti-dipper was higher in BD group (32.8％) than in EH group (16.7％)(x2 ＝7.894,P＜0.01).Among BD patients,anti-dipper who carried MM or MT genotypes (44.4 ％) was more than that who carried TT genotype (20.3％) (x2 ＝ 8.760,P＜ 0.01).Conclusions Fluctuations of nighttime blood pressure and diastolic pressure are higher in patients with BD,and the relative frequency of MM or MT genotype is higher.Moreover,among patients with BD who carried MM or MT genotypes are apt to have anti-dipper.MM or MT genotype is related to BD by means of affecting blood pressure circadian rhythms probably.

Drugs impact on CYP-450 enzyme family: A pharmacogenetical study of response variation.

Pharmacogenetics is the study of genetic basis in the individual response to drugs. A thorough knowledge of this will lead to a future where tailor-made drugs, suiting an individual, can be used. Scandinavian countries have been known for wide usage of pharmacogenetics and the most widely used application is for genotyping CYP2D6 in treating psychiatric illness. The CYP-450 enzyme, a super family of microsomal drug-metabolizing enzymes, is the most important of enzymes that catalyzes phase-I drug metabolism reaction. CYP2D6 is a member of this family and it has been most intensively studied and the best example of pharmacogenetics variation in drug metabolism. Neuro-transmitter and drug acting CNS viz. codeine, dextromethorphan, metoprolol and tryptyline etc. are well metabolized by this enzyme. Thus, CYP2D6 is one of the most important and responsible enzymes which regulates bioavailability and metabolism of drug. Presently 75 alleles of CYP2D6 have been described which are responsible for variance of metabolism and toxicity of drugs. Thus, by determining variance of CYP2D6 using molecular approaches viz., PCR, real-time PCR, DNA micro-array and molecular docking can determine the adverse effects, drug toxicity, bioavailability and therapeutic potential of new drug.

Single neucleotide polymorphisms of the vascular endothelial growth factor gene in Chinese Han population / 中国康复理论与实践

@#ObjectiveTo determine the distribution of the single neucleutide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) gene in Chinese Han population. Methods252 healthy Chinese Han subjects were studied with PCR technique. The results were compared with the data on European Caucasians reported. ResultsThe frequencies of VEGF gene allele C and A were respectively 71.8% and 28.2%. The genotypes of CC, CA and AA were 48.8%, 46.0% and 5.2%, respectively. The frequencies of VEGF promoter 2578A/A polymorphism in Chinese Han population were significantly different from those in European Caucasian population(P<0.01). Conclusion2578A/A homozygote which results to low VEGF expression of Chinese Han subjects is remarkably less than that of European Caucasians.

Study of honokiol's antagonising effect on calmodulin / 中国药理学通报

Using calmodulin dependent cyclic neucleotide phosphodiesterase and dansyl-labeled calmodulin,honokiol's action on calmodulin is studied. It is found that honokiol inhibits the activity of cyclic neucleotide phosphodiesterase induced by stimulus of calmodulin. With the increasing of calmodulin concentration, the IC50 value was increased. In the presence of Ca2+, honokiol reduces the fluorescence intensity of dansyl-calmodulin, and makes the spectrumpeaked red. The results indicate that honokiol can combine with calmodulin in the presence of Ca2+ and antagonise the effect caused by calmodulin's stimulation upon the phosphodiesterase. In addition , honokiol may exert its effect on the basal activity of calmodulin dependent cyclic neucleotide phosphodiesterase.

Purification and Characterization of Guanine Aminohydrolase from Rat Cerebrum

Guanine aminohydrolase(GAH;EC 3. 5. 4. 3.) was partially purified 122-fold from rat cerebrum to a specific activity of 7.22 in its per mg protein with a recovery of 7.47% by fractionation with ammonium sulfate, chromatography on DEAE-cellulose and hydroxyapatite, gel filtration on Sephadex G-200, and isoelectric focusing(pH4-6). The molecular weight of partially purified rat cerebral guanine aminohydrolase was estimated to be 110,000. But, in the cerebral cytosol, a rather higher molecular weight form of the enzyme was identified. The activity of the higher molecular weight form of guanine aminohydrolase was increased by dialyzing the cytosol, and it was converted into the lower molecular weight form(M.W.110,000) by addition of 2-mercaptoethanol. The reaction velocity of partially purified guanine aminohydrolase of rat cerebrum disclosed a hyperbolic curve, with its KM being 6.0uM at pH 8.0. The preparation showed high substrate specificity:among the purine nucleotides, nucleosides and bases with amino group, only guanosine and guanine were deaminated by the enzyme, and the reaction rate of the enzyme displayed by guanosine was less than 10% of that by guanine. When observed under the equimolar concentration of the substrate, hypoxanthine as well as inosine inhibited the activity of the rat cerebral guanine aminohydrolase by 9.4 and 7.8%, respectively, while 5-aminoimidazole-4-carboxamide inhibited the activity of it by 38%. The activity was inhibited by p-hydroxymercuric benzoate as well. Complete loss of its activity was observed after 30 minutes incubation at 60 degrees C, suggesting the preparation was heat labile.