No abstract

A rapid method combining gyrA PCR-restriction fragment length polymorphism analysis, parC PCR and adonitol fermentation was developed to identify Klebsiella pneumoniae phylogenetic groups KpI, KpII and KpIII. Analysis of 420 clinical isolates from 26 hospitals showed that the three groups were widespread geographically. KpI comprised 80.3% of 305 isolates from blood and 82.2-97.2% of isolates from other clinical sources. KpIII was never found among isolates from urinary tract infections. KpI isolates from blood were generally less susceptible than KpIII isolates to the ten antimicrobial agents tested, with KpII being intermediate. The frequencies of ceftazidime resistance were 21.6% and 8.6% in KpI and KpIII isolates, respectively (p 0.01).

HDL-associated paraoxonase type 1 (PON1) can protect LDL and HDL against oxidative modification in vitro and therefore may protect against cardiovascular disease. We investigated the effects of PON1 levels, activity, and genetic variation on high density lipoprotein-cholesterol (HDL-C) levels, circulating oxidized LDL (OxLDL), subclinical inflammation [high-sensitive C-reactive protein (Hs-CRP)], and carotid atherosclerosis. PON1 genotypes (L55M, Q192R, ؊ 107C/T, ؊ 162A/G, ؊ 824G/A, and ؊ 907G/C) were determined in 302 patients with familial hypercholesterolemia. PON1 activity was monitored by the hydrolysis rate of paraoxon, diazoxon, and phenyl acetate. PON1 levels, OxLDL, and Hs-CRP were determined using an immunoassay. The genetic variants of PON1 that were associated with high levels and activity of the enzyme were associated with higher HDL-C levels ( P values for trend: 0.008, 0.020, 0.042, and 0.037 for L55M, Q192R, ؊ 107C/T, and ؊ 907G/C, respectively). In addition to the PON1 genotype, there was also a positive correlation between PON1 levels and activity and HDL-C (PON1 levels: r ‫؍‬ 0.37, P Ͻ 0.001; paraoxonase activity: r ‫؍‬ 0.23, P ‫؍‬ 0.01; diazoxonase activity: r ‫؍‬ 0.29, P Ͻ 0.001; arylesterase activity: r ‫؍‬ 0.19, P ‫؍‬ 0.03). Our observations support the hypothesis that both PON1 levels and activity preserve HDL-C in plasma.

We measured plasma markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, and cholestanol) in order to compare the effects of maximal doses of rosuvastatin with atorvastatin and investigate the basis for the significant individual variation in lipid lowering response to statin therapy. Measurements were performed in participants (n 5 135) at baseline and after 6 weeks on either rosuvastatin (40 mg/day) or atorvastatin (80 mg/day) therapy. Plasma sterols were measured using gas-liquid chromatography. Rosuvastatin and atorvastatin significantly (P , 0.001) altered plasma total cholesterol (C) levels by 240%, and the ratios of lathosterol/C by 264% and 268%, and campesterol/C by 152% and 172%, respectively, with significant differences (P , 0.001) between the treatment groups for the latter parameter. When using absolute values of these markers, subjects with the greatest reductions in both synthesis (lathosterol) and absorption (campesterol) had significantly greater reductions in total C than subjects in whom the converse was true (246% versus 234%, P 5 0.001), with similar effects for LDL-C. Rosuvastatin and atorvastatin decreased markers of cholesterol synthesis and increased markers of fractional cholesterol absorption, with rosuvastatin having significantly less effect on the latter parameter than atorvastatin. In addition, alterations in absolute values of plasma sterols correlated with the cholesterol lowering response.-van Himbergen, T.

PON-1 Q192R, C-107T and L55M genotype, alcohol consumption, smoking and HDL levels are determinants of serum PON-1 phenotype. The contributions of the genetic markers to the PON-1 phenotype are stronger than the contributions of the lifestyle determinants.