Human serum paraoxonase 1 (PON1), a highdensity lipoprotein (HDL)-associated enzyme, has been shown to reduce the oxidation of low-density lipoprotein (LDL) and HDL by degrading lipid peroxides. This property of PON1 accounts for its ability to protect against atherosclerosis. In this study, we identified four polymorphisms in both the coding (L55M and Q192R) and regulatory regions (T-108C and G-909C) of the human PON1 gene in 202 healthy Thai individuals and investigated the influence of these polymorphisms on serum PON1 activity towards three substrates, namely, paraoxon, phenylacetate and diazoxon. The PON1 L55M, Q192R and G-909C polymorphisms significantly affected the variation in serum PON1 activity towards paraoxon. Serum PON1 activity towards paraoxon was significantly different among the genotype groups, as follows: 55LL > 55LM/55MM, 192RR > 192QR > 192QQ and À909CC > À909CG > À909GG. The PON1 Q192R and G-909C polymorphisms also influenced the variation in serum PON1 activity towards diazoxon but in the opposite direction to the activity towards paraoxon. Only the PON1 L55M polymorphism was associated with significant variation in serum PON1 activity towards phenylacetate while the PON1 T-108C polymorphism had no significant effect on serum PON1 activity towards any substrate. We also found linkage disequilibrium among the polymorphic sites, including Q192R versus L55M, Q192R versus T-108C and Q192R versus G-909C. Serum PON1 activity towards both paraoxon and phenylacetate, but not diazoxon, was positively correlated with HDL cholesterol (HDL-C) and apo AI concentrations. None of the PON1 polymorphisms significantly affected serum lipid, lipoprotein or apolipoprotein concentrations. Our findings suggest that the physiological relevance of the PON1 polymorphisms is that they are associated with significant differences in serum PON1 activity, and the impact of PON1 polymorphisms on this activity is substrate-dependent.
In 263 Asian patients with uncomplicated essential hypertension treated in general practice, once-daily amlodipine in a dose of 5 or 10mg provided significant antihypertensive efficacy either as monotherapy or in combination with other antihypertensive drugs while maintaining a favourable tolerability profile regardless of gender or age.
Background: The angiotensin II receptor antagonist irbesartan is an effective and well-tolerated treatment for hypertension in Western societies. However, evidence of the therapeutic benefits of angiotensin II receptor antagonists is generally lacking in hypertensive Asian subjects. Objectives: This multicentre, non-comparative study assessed the efficacy and safety of once-daily irbesartan in the treatment of hypertension in a population of Thai patients. Methods: After a 3- to 4-week placebo run-in period, patients were treated with irbesartan for 12 weeks, initially with 150 mg/day for 4 weeks. At 4 weeks, patients are up-titrated from irbesartan 150 to 300 mg/day and, at 8 weeks from irbesartan 150 to 300 mg/day or from irbesartan 300 mg to irbesartan 300 mg plus hydrochlorothiazide (HCTZ)12.5 mg/day if their seated diastolic blood pressure (SeDBP) remained ≧90 mm Hg. Trough blood pressures and safety assessments were measured at intervals during the study. The primary end point was the comparison of the reduction in blood pressure at the end of the placebo run-in and irbesartan treatment periods. Safety assessments formed part of the secondary end points. Results: Significantly greater reductions in SeDBP (14.42 versus 0.11 mm Hg, p < 0.0001) and seated systolic blood pressure (SeSBP) (20.83 versus 3.15 mm Hg, p < 0.0001) were reported after 12 weeks of irbesartan compared with the placebo run-in period. After 12 weeks, the blood pressure of 56% of patients on irbesartan regimens was normalized and 77% responded to therapy. These results were similar to irbesartan treatment in the Western population. Reductions in blood pressure were recorded in all the irbesartan treatment groups. The safety profile was globally similar to that observed during the placebo run-in period. Conclusions: Once-daily irbesartan was an effective and well-tolerated agent for the treatment of hypertension in Thai patients, suggesting that dose recommendations for irbesartan in Thailand should follow those used in Western countries.
This open-label, blinded study was performed to evaluate the efficacy and tolerability of barnidipine at a titrated dose of 10 -15 mg once daily for 8 weeks in the treatment of essential hypertension in 40 Thai patients. 'Office' blood pressure (BP) and 24-h ambulatory BP measurements were recorded. A systolic BP/ diastolic BP (SBP/DBP) reduction of 18.0 ± 13.6/9.1 ± 6.6 mmHg was obtained. The full response rate among patients with systolic and diastolic hypertension was 63% using either SBP or DBP criteria, and 54% using both SBP and DBP criteria. One of the two patients with isolated systolic hypertension had a full response, and the BP in two of the three patients with isolated diastolic hypertension was normalized. The trough-to-peak ratio and smoothness index for SBP/DBP were acceptable (0.76 ± 0.63/0.55 ± 0.26 and 1.2 ± 0.4/1.2 ± 0.3, respectively). In conclusion, once-daily barnidipine monotherapy provides effective 24-h BP control and is generally well tolerated in ambulatory patients.
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