WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• It has been suggested that the human paraoxonase-1 (PON1) genotype is an important determinant of the therapeutic response given to statin treatment.• It is also known that the PON1 activity status is a better predictor of coronary heart disease risk than any of the known PON1 genotypes.• Our goal was to answer this previously uninvestigated, still clinically relevant question: does the PON1 phenotype have an impact on the paraoxonase-activating and lipid-lowering effect of different types of statins. WHAT THIS STUDY ADDS• All the statins (atorvastatin, simvastatin and fluvastatin) included in this study were able to increase serum paraoxonase activity and decrease triglyceride levels effectively; however, this response seemed to be more significant in patients with AB+BB PON1 phenotype than in those bearing AA PON1 phenotype.• Furthermore, the apolipoprotein B-lowering effect of atorvastatin was also found to be PON1 phenotype-dependent.• Our results indicate that the PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on PON1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters. AimsHuman serum paraoxonase-1 (PON1) protects lipoproteins against oxidation by hydrolysing lipid peroxides in oxidized low-density lipoprotein, therefore it may protect against atherosclerosis. One of the two common PON1 gene polymorphisms within the PON1 gene is the Q192R, whose prevalence can be estimated by phenotype distribution analysis. The goal of this study was to clarify the role of PON1 phenotypes on the effect of three different statins on paraoxonase activity and lipid parameters. MethodsOne hundred and sixty-four patients with type IIb hypercholesterolaemia were involved in the study. We examined the effect of 10 mg day -1 atorvastatin, 10/20 mg day -1 simvastatin and 80 mg day -1 extended-release fluvastatin treatment on lipid levels and paraoxonase activity in patients with different PON1 phenotypes. The phenotype distribution of PON1 was determined by the dual substrate method. ResultsThree months of statin treatment significantly increased paraoxonase activity in every statin-treated group. In patients with AB+BB phenotype, statin treatment was significantly more effective on paraoxonase activity than in the AA group. Statin treatment more effectively decreased triglyceride levels in the AB+BB group compared with the AA group in the whole study population and in the simvastatin-treated group. Atorvastatin treatment was significantly more effective on apolipoprotein B levels in patients with AB+BB phenotype than in the AA phenotype group. ConclusionsThe PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on PON1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters.

Lactonase activity is a potential new predictor of cardiovascular risk in renal failure. Measurement of lactonase activity is recommended in future studies on HD and TRX patients.

Obesity as a pathogenic disorder is a predisposing factor for cardiovascular diseases and shows an increasing incidence in the industrialized countries. Adipokines such as leptin, adiponectin and resistin have a great impact on the development of atherosclerosis in obesity. Elevated levels of leptin have been found to be atherogenic whereas decreased levels of adiponectin have been proved to be anti-atherogenic in recent studies. The exact role of resistin in the process of atherosclerosis has so far remained uncertain and controversial. In our recent work, we studied the alteration in human paraoxonase-1 (PON1) activity and adipokine levels; furthermore, we also aimed at identifying the potential correlation between these parameters in this metabolic disorder. We investigated the abovementioned parameters both in adults and in children, with regard to the emerging role of childhood obesity and to get a clearer view of these factors during a whole lifetime. Investigating the adult population with a broad range of body mass index (BMI) we found significantly increased leptin and significantly decreased adiponectin and resistin levels and PON1 activity in the obese group compared to the lean controls. Adiponectin and resistin levels showed significantly positive correlation, while leptin and BMI showed significantly negative correlation with PON1 activity.Our findings were similar in childhood obesity: leptin showed significantly negative correlation, while adiponectin showed significantly positive correlation with PON1 activity. We found gender differences in the univariate correlations of leptin and adiponectin levels with PON1 activity in the adult population. In multiple regression analysis, adiponectin proved to be an independent factor of PON1 activity both in childhood and adult obesity, furthermore thiobarbituric acid-reactive substances (TBARS) also proved to be an independent predictor of the enzyme in adults, reflecting the important role of oxidative stress in obesity. Investigating PON 192 Q/R polymorphism by phenotypic distribution (A/B isoenzyme) in obese children, we found a significant correlation of PON1 arylesterase activity with leptin and adiponectin levels, and of body fat percentage with PON1 192 B isoenzyme.According to our studies, these metabolic changes in obesity predispose to the early development of atherosclerosis throughout our whole lifetime. Decreased activity of PON1 and alterations in adipokine levels in childhood obesity could contribute to an early commencement of this process, detected only later in adulthood by increased cardiovascular morbidity and mortality. Changed levels of leptin, adiponectin, resistin and PON1 activity at all ages, just like 192 Q/R polymorphism determined by phenotypic distribution, may be useful markers beside the general risk factors.Keywords (separated by '-') Adipokines -Leptin -Adiponectin -Resistin -Obesity -Paraoxonase-1 -Childhood Abstract Obesity as a pathogenic disorder is a predisposing factor for cardiovascular diseases and shows a...

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A diabeteses neuropathia egyik leggyakoribb és súlyos szövődmény lehet diabetes mellitusban. Az oxidatív stressz fontos szerepet játszik a cukorbetegség microvascularis komplikációinak progressziójában. A fokozott oxidatív stressz elősegíti bizonyos kóros metabolikus útvonalak, mint a poliol-és hexózamin-útvonal, az előrehaladott glikációs vég-termékek, a poli-ADP-ribóz polimeráz és a proteinkináz-C aktivációját. Jelen összefoglalóban a szerzők áttekintik az oxidatív stressz és a cukorbetegség kapcsolatának legfrissebb ismereteit és összegzik a fokozott oxidatív stressz patofiziológiai hatásait a diabeteses neuropathia kialakulásában. A diabeteses neuropathia kezelésében alkalmazott modern gyógyszerek vizsgálatában még intenzív, hosszú távú összehasonlító vizsgálatokra van szükség a közeljövőben. Orv. Hetil., 2016Hetil., , 157(49), 1939Hetil., -1946. Kulcsszavak: diabeteses neuropathia, oxidatív stressz, gyulladás, endothelialis diszfunkció, microvascularis szövőd-ményekThe role of oxidative stress in the development of diabetic neuropathy Diabetic neuropathy may be one of the most common and severe complications of diabetes mellitus. Oxidative stress plays a pivotal role in the development of microvascular complications of diabetes. The majority of related pathways like polyol and hexosamine, advanced glycation end products, poly-ADP-ribose polymerase, and protein kinase-C all originated from initial oxidative stress. In this review, the authors present the current oxidative stress hypothesis in diabetes mellitus and summarize the pathophysiological mechanisms of diabetic neuropathy associated with increased oxidative stress. The development of modern medicines to treat diabetic neuropathy needs intensive long-term comparative trials in the future. , F., M. Molnár, Á., Balogh, Z. [The role of oxidative stress in the development of diabetic neuropathy]. Orv. Hetil., 2016, 157(49), 1939-1946. (Beérkezett: 2016 elfogadva: 2016. október Rövidítések ADMA = aszimmetrikus dimetil-arginin; AGE-k = előrehala-dott glikációs végtermékek; DN = diabeteses neuropathia; GAPDH = glicerinaldehid-3-foszfát-dehidrogenáz; IL-1b/-6 = interleukin-1b/-6; MDA = malondialdehid; NFκB = nuclear factor kappa-light-chain-enhancer of activated B cells; NGF = idegi növekedési faktor; NO = nitrogén-monoxid; PAI-1 = 1-es típusú plazminogénaktivátor-inhibitor; PARP = poli(ADPribóz)-polimeráz; PKC = proteinkináz-C; RAGE = előrehala-dott glikációs végtermékek receptora; ROS = reaktív oxigén-gyökök; T2DM = 2-es típusú cukorbetegség; TBARS = tiobarbitursav-reaktív anyagok; TGF-β = transzformáló növe-kedési faktor-béta; TNF-α = tumornekrózis-faktor-alfa; VEGF = vascularis endothelialis növekedési faktor A polyneuropathiák gyűjtőfogalma alatt a perifériás és autonóm idegek degeneratív károsodását értjük, amely legtöbbször valamilyen anyagcsere-betegség vagy toxikus ártalom következtében alakul ki, leggyakoribb endo-ÖSSZEFOGLALÓ KÖZLEMÉNY Keywords: diabetic neuropathy, oxidative stress, inflammation, endothelial dysfunction, microvascular comp...

Abstract.Background: Human paraoxonase-1 (PON1) inhibits LDL-oxidation and atherogenesis, and possesses lactonase activity. Decreased PON1 activity was found in hemodialyzed and renal transplanted patients. Cystatin C plays a protective role in atherosclerosis, and is a new, sensitive marker of renal function. The relationship between these two markers in renal failure has not been investigated. Aims: The goal of this study was to clarify the relationship between PON1 activity, cystatin C and homocysteine in chronic renal failure. We also determined the levels of oxidatively modified LDL (oxLDL) and thiobarbituric acid reactive substances (TBARS) to characterize lipid peroxidation. Patients and methods: 74 hemodialized (HD), 171 renal transplanted patients (TRX), and 110 healthy controls (C) were involved in the study. PON1 activity and TBARS levels were measured spectrophotometrically. OxLDL level was determined with sandwich ELISA. Results: There was a negative correlation between PON1 activity and cystatin C level. Homocysteine level correlated negatively with PON1 activity, and positively with cystatin C level. OxLDL and TBARS levels were significantly higher in the HD and TRX groups compared to C. Conclusions: Cystatin C may be a good predictive factor not only for homocysteine levels but for the antioxidant status in patients with renal failure and renal transplantation.

Background/Aims: Human paraoxonase-1 (PON1) is responsible for the antioxidant effect of high-density lipoprotein (HDL) by inhibiting low-density lipoprotein oxidation. Previous studies discovered dyslipidemia (DL) and decreased PON1 activity in chronic renal failure (CRF). We aimed to determine PON and arylesterase activity, phenotypic distribution of the PON1 enzyme, and lipid profile in low and normal HDL cholesterol (HDL-C) patients with CRF, and renal transplant (TX), compared to primary DL. Methods: 116 CRF (low or normal HDL-C), 52 TX (low or normal HDL-C), and 62 DL patients (low or normal HDL-C) were included. PON and arylesterase activities were measured spectrophotometrically. Phenotype was determined using the dual substrate method. Results: Aryl/HDL-C was significantly higher in low HDL-C patients. Patients with CRF had significantly lower arylesterase activity compared to DL, independent of HDL-C. PON activity and PON/HDL-C did not differ significantly in CRF compared to TX and DL. Phenotypic distribution was similar in patient groups. Low HDL-C CRF patients had significantly lower cholesterol and triglyceride than DL. Conclusion: Decreased arylesterase activity, correlating with PON1 enzyme protein quantity, is not explicable by decreased HDL-C in CRF. Low HDL-C CRF patients’ increased cardiovascular morbidity is not attributable to changes in PON1 activity, or phenotypic distribution.