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Sample records for human paraoxonase pon1

  1. In vitro inhibition effect of some coumarin compounds on purified human serum paraoxonase 1 (PON1).

    Science.gov (United States)

    Gokce, Basak; Gencer, Nahit; Arslan, Oktay; Karatas, Mert Olgun; Alici, Bulent

    2016-08-01

    Human serum paraoxonase 1 (PON1; EC 3.1.8.1) is a high-density lipoprotein associated, calcium-dependent enzyme that hydrolyses aromatic esters, organophosphates and lactones and can protect the low-density lipoprotein against oxidation. In this study, in vitro effect of some hydroxy and dihydroxy ionic coumarin derivatives (1-20) on purified PON1 activity was investigated. Among these compounds, derivatives 11-20 are water soluble. In investigated compounds, compounds 6 and 13 were found the most active (IC50 = 35 and 34 µM) for PON1, respectively. The present study has demonstrated that PON1 activity is very highly sensitive to studied coumarin derivatives.

  2. Impact of antibacterial drugs on human serum paraoxonase-1 (hPON1) activity:an in vitro study

    Institute of Scientific and Technical Information of China (English)

    Hakan Syt; Elif Duygu Kaya; kr Beydemir

    2014-01-01

    Objective:To investigate the in vitro effects of the antibacterial drugs, meropenem trihydrate, piperacillin sodium, and cefoperazone sodium, on the activity of human serum paraoxonase Methods: hPON1 was purified from human serum using simple chromatographic methods, including DEAE-Sephadex anion exchange and Sephadex G-200 gel filtration chromatography. Results:The three antibacterial drugs decreased in vitro hPON1 activity. Inhibition mechanisms meropenem trihydrate was noncompetitive while piperacillin sodium and cefoperazone sodium were competitive. Conclusions:Our results showed that antibacterial drugs significantly inhibit hPON1 activity, both in vitro, with rank order meropenem trihydrate piperacillin sodium cefoperazone sodium in vitro.

  3. Paraoxonase activity against nerve gases measured by capillary electrophoresis and characterization of human serum paraoxonase (PON1) polymorphism in the coding region (Q192R).

    Science.gov (United States)

    Kanamori-Kataoka, Mieko; Seto, Yasuo

    2009-02-01

    An analytical method for determining paraoxonase activity against sarin, soman and VX was established. We used capillary electrophoresis to measure directly the hydrolysis products: alkyl methylphosphonates. After enzymatic reaction of human serum paraoxonase (PON1) with nerve gas, substrate was removed with dichloromethane, and alkyl methylphoshphonates were quantified by capillary electrophoresis of reversed osmotic flow using cationic detergent and sorbic acid. This method was applied to the characterization of human serum PON1 polymorphism for nerve gas hydrolytic activity in the coding region (Q192R). PON1-192 and PON1-55 genotypes were determined by their gel electrophoretic fragmentation pattern with restriction enzymes after polymerase chain reaction (PCR) of blood leukocyte genomic DNA. Frequencies of genotypes among 63 members of our institutes with PON1-192 and PON1-55 were 9.5% ((192)QQ), 30.1% ((192)QR) and 44.4% ((192)RR), and 82.5% ((55)LL), 17.5% ((55)LM) and 0% ((55)MM), respectively. (192)Q and (192)R enzymes were purified from the respective genotype human plasma, using blue agarose affinity chromatography and diethyl amino ethane (DEAE) anion exchange chromatography. V(max) and K(m) were measured using Lineweaver-Burk plots for hydrolytic activities against sarin, soman and VX at pH 7.4 and 25 degrees C. For sarin and soman, the V(max) for (192)Q PON1 were 3.5- and 1.5-fold higher than those for (192)R PON1; and k(cat)/K(m) for (192)Q PON1 were 1.3- and 2.8-fold higher than those for (192)R PON1. For VX, there was little difference in V(max) and k(cat)/K(m) between (192)Q and (192)R PON1, and VX hydrolyzing activity was significantly lower than those for sarin and soman. PON1 hydrolyzed sarin and soman more effectively than paraoxon.

  4. Novel nucleophiles enhance the human serum paraoxonase 1 (PON1)-mediated detoxication of organophosphates.

    Science.gov (United States)

    Chambers, Janice E; Chambers, Howard W; Meek, Edward C; Funck, Kristen E; Bhavaraju, Manikanthan H; Gwaltney, Steven R; Pringle, Ronald B

    2015-01-01

    Paraoxonase 1 (PON1) is a calcium-dependent hydrolase associated with serum high-density lipoprotein particles. PON1 hydrolyzes some organophosphates (OPs), including some nerve agents, through nucleophilic attack of hydroxide ion (from water) in the active site. Most OPs are hydrolyzed inefficiently. This project seeks to identify nucleophiles that can enhance PON1-mediated OP degradation. A series of novel nucleophiles, substituted phenoxyalkyl pyridinium oximes, has been synthesized which enhance the degradation of surrogates of sarin (nitrophenyl isopropyl methylphosphonate; NIMP) and VX (nitrophenyl ethyl methylphosphonate; NEMP). Two types of in vitro assays have been conducted, a direct assay using millimolar concentrations of substrate with direct spectrophotometric quantitation of a hydrolysis product (4-nitrophenol) and an indirect assay using submicromolar concentrations of substrate with quantitation by the level of inhibition of an exogenous source of acetylcholinesterase from non-hydrolyzed substrate. Neither NIMP nor NEMP is hydrolyzed effectively by PON1 if one of these novel oximes is absent. However, in the presence of eight novel oximes, PON1-mediated degradation of both surrogates occurs. Computational modeling has created a model of PON1 embedded in phospholipid and has indicated general agreement of the binding enthalpies with the relative efficacy as PON1 enhancers. PON1 enhancement of degradation of OPs could be a unique and unprecedented mechanism of antidotal action.

  5. In vitro inhibition effect of some dihydroxy coumarin compounds on purified human serum paraoxonase 1 (PON1).

    Science.gov (United States)

    Erzengin, Mahmut; Basaran, Ismet; Cakir, Umit; Aybey, Aynur; Sinan, Selma

    2012-11-01

    Human serum paraoxonase 1 (PON1; EC 3.1.8.1) is a high-density lipoprotein associated, calcium-dependent enzyme that hydrolyses aromatic esters, organophosphates and lactones and can protect the low-density lipoprotein against oxidation. In this study, in vitro inhibition effect of some dihydroxy coumarin compounds namely 6,7-dihydroxy-3-(2-methylphenyl)-2H-chromen-2-one (A), 6,7-dihydroxy-3-(3-methylphenyl)-2H-chromen-2-one (B) and 6,7-dihydroxy-3-(4-methylphenyl)-2H-chromen-2-one (C) on purified PON1 were investigated by using paraoxon as a substrate. PON1 was purified using two-step procedures, namely ammonium sulphate precipitation and Sepharose-4B-L-tyrosine-1-naphthylamine hydrophobic interaction chromatography. The purified enzyme had a specific activity of 11.76 U/mg. The dihydroxy coumarin derivatives of A and B compounds inhibited PON1 enzyme activity in a noncompetitive inhibition manner with K(i) of 0.0080±0.256 and 0.0003±0.018 mM values, respectively. C compound exerted an uncompetitive inhibition of PON1 enzyme activity with K(i) of 0.0010±0.173 mM. Moreover, dihydroxy coumarin derivatives of A, B and C compounds were effective inhibitors on purified human serum PON1 activity with IC(50) of 0.012, 0.022 and 0.003 mM values, respectively. IC(50) value of unsubstituted 6,7 dihydroxy coumarin was found as 0.178 mM. The present study has demonstrated that PON1 activity is very highly sensitive to studied coumarin derivatives.

  6. Impact of antibacterial drugs on human serum paraoxonase-1(hPON1)activity:an in vitro study

    Institute of Scientific and Technical Information of China (English)

    Hakan; Syt; Elif; Duygu; Kaya; Skr; Beydemir

    2014-01-01

    Objective:To investigate the in vitro effects of the antihacterial drugs,mcropenem trihydrate.piperacillin sodium,and cefoperazone sodium,on the activity of human serum paraoxonase mPOND.Methods:hPQN1 was purified from human serum using simple chromatographic methods.including DEAE-Sephadex anion exchange and Sephadex G-200 gel filtration chromatography.Results:The three antihacterial drugs decreased in vitro hPON1 activity.Inhibition mechanisms meropcnem trihydrate was noncompetitive while piperacillin sodium and cefoperazone sodium were competitive.Conclusions:Our results showed that antihacterial drugs significantly inhibit hPON1 activity,both in vitro,with rank order meropenem trihydrate piperacillin sodium cefoperazone sodium in vitro.

  7. Role of paraoxonase 1 (PON1) in organophosphate metabolism: Implications in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Androutsopoulos, Vasilis P. [Center of Toxicology Science and Research, University of Crete, Heraklion, Crete (Greece); Kanavouras, Konstantinos [Laboratory of Neurological Sciences, University of Crete, Heraklion, Crete (Greece); Tsatsakis, Aristidis M., E-mail: aris@med.uoc.gr [Center of Toxicology Science and Research, University of Crete, Heraklion, Crete (Greece)

    2011-11-15

    Organophosphate pesticides are a class of compounds that are widely used in agricultural and rural areas. Paraoxonase 1 (PON1) is a phase-I enzyme that is involved in the hydrolysis of organophosphate esters. Environmental poisoning by organophosphate compounds has been the main driving force of previous research on PON1 enzymes. Recent discoveries in animal models have revealed the important role of the enzyme in lipid metabolism. However although PON1 function is well established in experimental models, the contribution of PON1 in neurodegenerative diseases remains unclear. In this minireview we summarize the involvement of PON1 genotypes in the occurrence of Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. A brief overview of latest epidemiological studies, regarding the two most important PON1 coding region polymorphisms PON1-L55M and PON1-Q192R is presented. Positive and negative associations of PON1 with disease occurrence are reported. Notably the MM and RR alleles contribute a risk enhancing effect for the development of some neurodegenerative diseases, which may be explained by the reduced lipoprotein free radical scavenging activity that may give rise to neuronal damage, through distinct mechanism. Conflicting findings that fail to support this postulate may represent the human population ethnic heterogeneity, different sample size and environmental parameters affecting PON1 status. We conclude that further epidemiological studies are required in order to address the exact contribution of PON1 genome in combination with organophosphate exposure in populations with neurodegenerative diseases.

  8. Human serum paraoxonase-1 (hPON1): in vitro inhibition effects of moxifloxacin hydrochloride, levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium.

    Science.gov (United States)

    Türkeş, Cüneyt; Söyüt, Hakan; Beydemir, Şükrü

    2015-01-01

    In this study, we investigated the effects of antibacterial drugs (moxifloxacin hydrochloride, levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium) on human serum paraoxonase-1 (hPON1) enzyme activity from human serum in vitro conditions. For this purpose, hPON1 enzyme was purified from human serum using simple chromatographic methods. The antibacterial drugs exhibited inhibitory effects on hPON1 at low concentrations. Ki constants were calculated to be 2.641 ± 0.040 mM, 5.525 ± 0.817 mM, 35.092 ± 1.093 mM, 252.762 ± 5.749 mM and 499.244 ± 10.149 mM, respectively. The inhibition mechanism of moxifloxacin hydrochloride was competitive, whereas levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium were noncompetitive inhibitors.

  9. Paraoxonase 1 (PON1) Status and Risk of Insecticide Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Furlong, Clement E.; Cole, Toby B.; Walter, Betsy J.; Shih, Diana M.; Tward, Aaron; Lusis, Aldons J.; Timchalk, Chuck; Richter, Rebecca J.; Costa, Lucio G.

    2005-06-23

    Paraoxonase 1 (PON1) is an HDL associated enzyme that catalyzes a number of different reactions including the hydrolysis of the toxic oxon metabolites of the insecticides diazinon and chlorpyrifos. PON1 has also been implicated in the detoxication of oxidized lipids and the metabolism of a number of drugs, activating some, while inactivating others. There are two common PON1 coding region polymorphisms (L55M and Q192R). The latter determines the catalytic efficiency of hydrolysis of a number of substrates including chlorpyrifos oxon, but not diazoxon. Evidence for the physiological importance of PON1 in modulating exposures to these two insecticides comes from several different studies. Early studies noted that species with high levels of PON1 were much more resistant to certain organophosphorus (OP) insecticides than were species with low levels. Another early study by Main demonstrated that injected rabbit paraoxonase protected rats from paraoxon toxicity. Our research group began the development of a mouse model system for examining the importance of PON1 in the detoxication of OP insecticides.

  10. Lead Exposure Is Associated with Decreased Serum Paraoxonase 1 (PON1) Activity and Genotypes

    OpenAIRE

    Li, Wan-Fen; Pan, Mei-Hung; Chung, Meng-Chu; Ho, Chi-Kung; Chuang, Hung-Yi

    2006-01-01

    Lead exposure causes cardiac and vascular damage in experimental animals. However, there is considerable debate regarding the causal relationship between lead exposure and cardiovascular dysfunction in humans. Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing oxidized lipids and thus protects against atherosclerosis. Previous studies have shown that lead and several other metal ions are able to inhibit PON1 activity in vitro. To investig...

  11. Paraoxonase-1 (PON1) status in pancreatic cancer: relation to clinical parameters.

    Science.gov (United States)

    Vecka, M; Jáchymová, M; Vávrová, L; Kodydková, J; Macášek, J; Urbánek, M; Krechler, T; Slabý, A; Dušková, J; Muravská, A; Zák, A

    2012-01-01

    Human paraoxonase 1 (PON1) has been shown to decrease the level of systemic oxidative stress, which is thought to contribute to cancer development. The aim of this study was to examine the interrelationships between PON1 status and some clinical characteristics in patients with pancreatic cancer (PC). A group of 73 consecutive patients with PC (stage II-IV) and 73 control subjects were examined. Laboratory studies included five polymorphisms of the PON1 gene (L55M, Q192R, -108C/T, -126C/T, and -162A/G), PON1 arylesterase (PON1-A) and lactonase (PON1-L) activities, as well as some markers of protein metabolism, insulin resistance, and oxidative stress. In comparison with the control group, no difference in the distribution of the PON1 polymorphisms was found in cancer patients, both arylesterase and lactonase activities being significantly lower (-33, -47 %, respectively, both P < 0.001). There was neither statistically significant association of PON1 polymorphisms with tumour stages nor with diabetes mellitus connected with PC. The genotype distribution of L55M and ‑108C/T differed only in a subgroup of patients presenting clinically relevant malnutrition (χ² = 6.50, 6.25, respectively, both P < 0.05). In the PC group, PON1-A and PON1-L activities correlated with Nutritional Risk Index (r = 0.351, 0.409, respectively, both P < 0.01), PON1-L with mid-arm muscle circumference (r = 0.328, P < 0.05), and PON1-A and PON1-L with serum albumin (r = 0.352, 0.391 respectively, both < 0.01). Our results suggest that PON1 plays an important role in PC, especially in cancer-associated malnutrition.

  12. Interethnic variability of plasma paraoxonase (PON1) activity towards organophosphates and PON1 polymorphisms among Asian populations--a short review.

    Science.gov (United States)

    Mohamed Ali, Safiyya; Chia, Sin Eng

    2008-08-01

    Organophosphate (OP) poisoning is a progressively worrying phenomenon as worldwide pesticide production and consumption has doubled. On average, WHO estimates that 3% of agricultural workers in developing Asian countries suffer an episode of pesticide poisoning every year. Furthermore, the threat of OP usage in terrorism is existent, as seen by the subway tragedy in Tokyo in 1995 where sarin was used. Despite these alarming facts, there is currently no global system to track poisonings related to pesticide use. Human serum paraoxonase (PON1) is the enzyme that hydrolyses OP compounds. Serum PON1 levels and activity vary widely among different ethnic populations. Two commonly studied polymorphisms of PON1 are PON1Q192R and PON1L55M. PON1R192 hydrolyses paraoxon faster than PON1Q192 but hydrolyses diazoxon, sarin and soman eight times slower, and vice versa. PON1M55 has lower plasma levels of PON1 than PON1L55. As the prevalence of the different alleles and genotypic distribution vary between the Asian populations we studied, we propose the necessity to study PON1 polymorphisms and its role in OP toxicity in Asian populations. This would help safeguard the proper care of agricultural workers who might be affected by OP poisoning, and alert relevant anti biological terrorism agencies on possible risks involved in the event of an OP attack and provide effective counter measures.

  13. Lead exposure is associated with decreased serum paraoxonase 1 (PON1) activity and genotypes.

    Science.gov (United States)

    Li, Wan-Fen; Pan, Mei-Hung; Chung, Meng-Chu; Ho, Chi-Kung; Chuang, Hung-Yi

    2006-08-01

    Lead exposure causes cardiac and vascular damage in experimental animals. However, there is considerable debate regarding the causal relationship between lead exposure and cardiovascular dysfunction in humans. Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing oxidized lipids and thus protects against atherosclerosis. Previous studies have shown that lead and several other metal ions are able to inhibit PON1 activity in vitro. To investigate whether lead exposure has influence on serum PON1 activity, we conducted a cross-sectional study of workers from a lead battery manufactory and lead recycling plant. Blood samples were analyzed for whole-blood lead levels, serum PON1 activity, and three common PON1 polymorphisms (Q192R, L55M, -108C/T). The mean blood lead level (+/-SD) of this cohort was 27.1+/-15 microg/dL. Multiple linear regression analysis showed that blood lead levels were significantly associated with decreased serum PON1 activity (p<0.001) in lead workers. This negative correlation was more evident for workers who carry the R192 allele, which has been suggested to be a risk factor for coronary heart disease. Taken together, our results suggest that the decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis, particularly subjects who are homozygous for the R192 allele.

  14. The role of genetic (PON1 polymorphism) and environmental factors, especially physical activity, in antioxidant function of paraoxonase.

    Science.gov (United States)

    Otocka-Kmiecik, Aneta; Orłowska-Majdak, Monika

    2009-12-30

    Paraoxonase 1 (PON1) is a member of a three-gene family (PON1, PON2, and PON3). PON1 activity dominates in human plasma. It is secreted from hepatic cells and is found in the circulation bound to high-density lipoproteins (HDLs). For many years it has been known only for its ability to hydrolyze organophosphate derivatives. More recently, PON1's antioxidant activity draws attention as the enzyme was described to prevent oxidation of lipoproteins by reactive oxygen species formed during oxidative stress. PON1 was also shown to hydrolyze atherogenic products of oxidative lipid modification such as phospholipid peroxides and cholesterol ester hydroperoxides. Some studies indicate that the enzyme presents a lipolactonase activity and hydrolyzes homocysteine thiolactone (HCTL). There is growing evidence as to PON1's protective role in atherosclerosis. Genetic (PON1 polymorphism) and environmental factors and lifestyle may influence PON1 blood concentration and biological activity. Among the many recognized factors accounting for lifestyle, physical activity plays an important role. Various, often opposite, effects on PON1 status are observed in regular training and single physical activities. The results of different studies are often contradictory. It may depend on the time, intensity, and frequency of physical activity. Additionally, it seems that the effects of physical activity on PON1 blood concentration and activity are modified by environmental and lifestyle factors as well as PON1 polymorphism.

  15. Paraoxonase (PON1) polymorphisms Q192R and L55M are not associated with human longevity: A meta-analysis.

    Science.gov (United States)

    Wei, Gan-Zhong; Zhu, Mei-Yan; Wang, Fang; Zhao, Yue-Guang; Li, Shan-Shan; Liu, Tong-Yang; Luo, Ying; Tang, Wen-Ru

    2016-01-01

    Genetic mutations in the paraoxonase 1 (PON1) encoding gene have been considered to affect mortality and of these the functional promoter region polymorphisms Q192R and L55M are among the most widely studied. The aim of this study was to determine whether the Q192R and L55M polymorphisms of PON1 can increase susceptibility to longevity. A meta-analysis was performed to obtain a comprehensive estimation of the association between Q192R and L55M and longevity in long-lived individuals (LLIs) aged 80 years or more. A search was carried out in the PubMed database (from January 2001 to May 2014) to obtain data on the role of PON1 polymorphisms in longevity and a pooled odds ratio (OR) with a 95% confidence interval (CI) was used to assess the associations. The meta-analysis was based on 9 studies of PON1 Q192R and 5 studies of PON1 L55M that covered a total of 5086 LLIs and 4494 controls. Overall, significantly increased risks were not observed for either Q192R or L55M. The results of the statistical calculations were as follows: R vs. Q (additive model): OR = 1.080, 95% CI = 0.989-1.179, p = 0.088 and RR + RQ vs. QQ (dominant model): OR = 1.099, 95% CI = 0.975-1.240, p = 0.124; M vs. L (additive model): OR = 0.946, 95% CI = 0.862-1.039, p = 0.245 and MM + ML vs. LL (dominant model): OR = 0.951, 95% CI = 0.836-1.081, p = 0.442 for Q192R and L55M, respectively. The results did not change with an age cut-off among the LLIs of ≥ 93 years. No evidence that the Q192R and L55M polymorphisms of PON1 impacted on the probability of reaching extreme ages was found although this cannot be completely ruled out; however, the possibility of population-specific effects due to the influence of and interaction between different genes or environmental factors could not be ruled out.

  16. Paraoxonase (PON1 and PON3 polymorphisms: impact on liver expression and atorvastatin-lactone hydrolysis

    Directory of Open Access Journals (Sweden)

    Stephan eRiedmaier

    2011-07-01

    Full Text Available Atorvastatin δ-lactone, a major, pharmacologically inactive metabolite, has been associated with toxicity. In a previous study we showed that polymorphisms of UGT1A3 influence atorvastatin δ-lactone formation. Here we investigated the reverse reaction, atorvastatin δ-lactone hydrolysis, in a human liver bank. Screening of microarray data revealed paraoxonases PON1 and PON3 among 17 candidate esterases. Microsomal δ-lactone hydrolysis was significantly correlated to PON1 and PON3 protein (rs=0.60; rs=0.62, respectively; P<0.0001. PON1 and PON3 were strongly correlated to each other (rs=0.60 but PON1 was shown to be more extensively glycosylated than PON3. In addition a novel splice variant of PON3 was identified. Genotyping of 40 polymorphisms within the PON-locus identified PON1 promoter polymorphisms (-108T>C, -832G>A, -1741G>A and a tightly linked group of PON3 polymorphisms (-4984A>G, -4105G>A, -1091A>G, -746C>T and F21F to be associated with changes in atorvastatin δ-lactone hydrolysis and expression of PON1 but not PON3. However, carriers of the common PON1 polymorphisms L55M or Q192R showed no difference in δ-lactone hydrolysis or PON expression. Haplotype analysis revealed decreased δ-lactone hydrolysis in carriers of the most common haplotype *1 compared to carriers of haplotypes *2, *3, *4 and *7. Analysis of non-genetic factors showed association of hepatocellular and cholangiocellular carcinoma with decreased PON1 and PON3 expression, respectively. Increased C-reactive protein and γ-glutamyl transferase levels were associated with decreased protein expression of both enzymes, and increased bilirubin levels, cholestasis and pre-surgical exposure to omeprazole or pantoprazole were related to decreased PON3 protein. In conclusion, PON-locus polymorphisms affect PON1 expression whereas non-genetic factors have an effect on PON1 and PON3 expression. This may influence response to therapy or adverse events in statin treatment.

  17. Monocyte-macrophage membrane possesses free radicals scavenging activity: stimulation by polyphenols or by paraoxonase 1 (PON1).

    Science.gov (United States)

    Rosenblat, M; Elias, A; Volkova, N; Aviram, M

    2013-04-01

    In the current study, we analysed free radicals scavenging activity of monocytes-macrophages in the absence or presence of antioxidants such as polyphenols or paraoxonase 1 (PON1). THP-1 human monocytic cell line, murine J774A.1 macrophages, as well as human primary monocytes have the capability to scavenge free radicals, as measured by the 1-diphenyl-2-picryl-hydrazyl (DPPH) assay. This effect (which could be attributed to the cell's membrane) was cell number and incubation time dependent. Upon incubation of J774A.1 macrophages with acetylated LDL (Ac-LDL), with VLDL, or with the radical generator, AAPH, the cells' lipid peroxides content, and paraoxonase 2 (PON2) activity were significantly increased. While non-treated cells decreased DPPH absorbance by 65%, the Ac-LDL-, VLDL- or AAPH-treated cells, decreased it by only 33%, 30%, or 45%, respectively. We next analysed the effect of J774A.1 macrophage enrichment with antioxidants, such as polyphenols or PON1 on the cells' free radicals scavenging activity. Non-treated cells decreased DPPH absorbance by 50%, whereas vitamin E-, punicalagin- or PJ-treated cells significantly further decreased it, by 75%. Similarly, in PON1-treated cells DPPH absorbance was further decreased by 63%, in association with 23% increment in PON1 catalytic activity. In cells under oxidative stress [treated with AAPH-, or with oxidized LDL], PON1 activity was decreased by 31% or 40%, as compared to the activity observed in PON1 incubated with non-treated cells. We conclude that monocytes-macrophages possess free radicals scavenging activity, which is decreased under atherogenic conditions, and increased upon cell enrichment with potent antioxidants such as nutritional polyphenols, or PON1.

  18. In vitro inhibition of the paraoxonase from human serum with ...

    African Journals Online (AJOL)

    SERVER

    2008-03-04

    Mar 4, 2008 ... Sulfonamide was an effective inhibitor on purified human serum PON1 activity for phenylacetate and paraoxon .... efficiency (kcat/KM≈10. 4 M-1, s-1). .... Directed evolution of mammalian paraoxonases PON1 and PON3 for.

  19. Paraoxonase in cardiovascular disease : actions and interactions

    NARCIS (Netherlands)

    Himbergen, Thomas Mattheus van

    2006-01-01

    Paraoxonase type 1 (PON1) is an enzyme which belongs to the family of paraoxonases. Other members of the paraoxonase family are PON2 and PON3. In the human body, PON1 is located exclusively on the high-density lipoprotein (HDL) particle. As the name 'paraoxonase' indicates, PON1 can hydrolyze the h

  20. Paraoxonase 1 (PON1 polymorphisms, haplotypes and activity in predicting cad risk in North-West Indian Punjabis.

    Directory of Open Access Journals (Sweden)

    Nidhi Gupta

    Full Text Available Human serum paraoxonase-1 (PON1 prevents oxidation of low density lipoprotein cholesterol (LDL-C and hydrolyzes the oxidized form, therefore preventing the development of atherosclerosis. The polymorphisms of PON1 gene are known to affect the PON1 activity and thereby coronary artery disease (CAD risk. As studies are lacking in North-West Indian Punjabi's, a distinct ethnic group with high incidence of CAD, we determined PON1 activity, genotypes and haplotypes in this population and correlated them with the risk of CAD.350 angiographically proven (≥ 70% stenosis CAD patients and 300 healthy controls were investigated. PON1 activity was determined towards paraoxon (Paraoxonase; PONase and phenylacetate (Arylesterase; AREase substrates. In addition, genotyping was carried out by using multiplex PCR, allele specific oligonucleotide -PCR and PCR-RFLP methods and haplotyping was determined by PHASE software. The serum PONase and AREase activities were significantly lower in CAD patients as compared to the controls. All studied polymorphisms except L55M had significant effect on PONase activity. However AREase activity was not affected by them. In a logistic regression model, after adjustment for the conventional risk factors for CAD, QR (OR: 2.73 (1.57-4.72 and RR (OR, 16.24 (6.41-41.14 genotypes of Q192R polymorphism and GG (OR: 2.07 (1.02-4.21 genotype of -162A/G polymorphism had significantly higher CAD risk. Haplotypes L-T-G-Q-C (OR: 3.25 (1.72-6.16 and L-T-G-R-G (OR: 2.82 (1.01-7.80 were also significantly associated with CAD.In conclusion this study shows that CAD patients had lower PONase and AREase activities as compared to the controls. The coding Q192R polymorphism, promoter -162A/G polymorphism and L-T-G-Q-C and L-T-G-R-G haplotypes are all independently associated with CAD.

  1. Effects of aerobic training on serum paraoxonase activity and its relationship with PON1-192 phenotypes in women

    Institute of Scientific and Technical Information of China (English)

    Gulbin Rudarli Nalcakan; S. Rana Varol; Faruk Turgay; Mesut Nalcakan; M. Zeki Ozkol; S. Oguz Karamizrak

    2016-01-01

    Background: Paraoxonase 1 (PON1) is an antioxidant enzyme that protects high-density lipoprotein (HDL) and low-density lipoprotein against oxidation. Limited studies have addressed the influenc of exercise on PON1 activity and its relationship with PON1 phenotypes. We investigated relationships between PON1-192 phenotypes, PON1 activity, aerobic exercise, and blood lipid and lipoprotein concentrations in middle-aged women. Methods: An exercise group (n=50) engaging in regular aerobic exercise and a control group (n=41) were selected from a subset of 300 Caucasian women that met the inclusion criteria. Serum PON1, salt-stimulated PON1 (SSPON1), and arylesterase (ARE) activities;cholesterol levels and ARE activities of total HDL and HDL subgroups (HDLs) (supernatants obtained by polyethylene glycol);and blood lipid and lipoprotein concentrations were determined by standardized enzymatic methods. PON1-192 QQ (low activity), QR (moderate activity), and RR (high activity) phenotype groups were define using serum SSPON1/ARE activity ratios. The R-carries (RC) phenotype group consisted of the QR and RR groups combined. Results: All lipid and lipoprotein concentrations were greater in the exercise group than in the control group. Regardless of phenotype, no significan differences were observed between the exercise and control groups in terms of serum PON1, SSPON1, or ARE activity associated with HDLs (p>0.05), whereas PON1 activities in QQ-phenotyped women in the exercise group were significant y higher than those in the control group (p Conclusion: These results showed that a regular aerobic exercise program can improve PON1 activity depending on PON1-192 phenotype, but not on lipid and lipoprotein levels, in middle-aged Turkish women.

  2. Q192R Paraoxonase (PON)1 Polymorphism, Insulin Sensitivity, and Endothelial Function in Essential Hypertensive Men

    Science.gov (United States)

    Dell’Omo, Giulia; Penno, Giuseppe; Pucci, Laura; Lucchesi, Daniela; Prato, Stefano Del; Pedrinelli, Roberto

    2014-01-01

    AIMS Essential hypertension is characterized by increased reactive oxygen species (ROS) generation harmful for insulin sensitivity and nitric oxide (NO)-mediated vasomotor function, a noxious effect that paraoxonase (PON)1, an antioxidant circulating high-density lipoprotein (HDL)-bound esterase, may counteract. The PON1 gene contains several polymorphisms including a glutamine (Q) to arginine (R) transition at position 192 encoding circulating allozymes with higher antioxidant activity that might influence both parameters. METHODS Q192R was determined by polymerase chain reaction in 72 never-treated, glucose-tolerant, uncomplicated essential hypertensive men. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) and endothelial function by forearm vasodilation (strain-gage venous plethysmography) to intra-arterial acetylcholine (ACH) with sodium nitroprusside (NIP) as a NO-independent control. Additional evaluation variables included 24-hour blood pressure (BP), lipids, BMI, smoking status, and metabolic syndrome (MetS) by Adult Treatment Panel (ATP)-III criteria. R192 was considered as the rare allele, and its associations analyzed by dominant models (Q/Q vs. Q/R + R/R). RESULTS Genotype frequencies were consistent with the Hardy–Weinberg equilibrium. HOMA was lower and insulin resistance (the upper fourth of HOMA values distribution) less prevalent in Q/R + R/R carriers in whom ACH-mediated vasodilatation was greater and endothelial dysfunction (the bottom fourth of ACHAUC values distribution) less frequent than in Q/Q homozygotes. Q192R polymorphism and MetS were unrelated parameters despite their common association with insulin resistance. 24-hour BP, BMI, lipids, and smoking habits were homogeneously distributed across genotypes. CONCLUSIONS Q192R polymorphism associates differentially with insulin sensitivity and endothelial function in essential hypertensive men. PMID:25089090

  3. ESTABLISHMENT OF PARAOXONASE AND ARYLESTERASE ACTIVITY OF PARAOXONASE 1 (PON1 IN DEPENDENCE ON 55(L/M AND 192(Q/R DNA POLYMORPHISM IN ADULT PEOPLE WITH DOWN SYNDROME

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    Pavel SÝKORA

    2010-04-01

    Full Text Available Human serum paraoxonase 1 is a calcium-dependent esterase located on high density lipoproteins (HDL. It inhibits LDL peroxidation and hydrolysis of oxide forms of phospholipides and therefore significantly affects the development of ateroscletosis. The aim of this study was to establish the paraoxonase and arylesterase activity of PON1 in adult people with Down syndrome (DS. Adults with DS (10 men and 10 women ages 16 to 37 years participated and were compared to a control group (10 men and 10 women age ranging from 17 to 45 years. The 55(L/M and 192(Q/R DNA polymorphism (PCR-RFLP method and paraoxonase and arylesterase activity was investigated in every patient. The results showed the reduction of PON1 activity in people with DS, in contrast to the decreased development of atherosclerosis in DS. Therefore it can be concluded, that PON1 does not have a direct effect on the lower prevalence of atherosclerosis in people with DS.

  4. Dietary antioxidants (selenium and N-acetylcysteine) modulate paraoxonase 1 (PON1) in PCB 126-exposed rats.

    Science.gov (United States)

    Shen, Hua; Li, Miao; Wang, Bingxuan; Lai, Ian K; Robertson, Larry W; Ludewig, Gabriele

    2014-05-01

    Environmental pollutants polychlorinated biphenyls (PCBs), especially dioxin-like PCBs, cause oxidative stress and associated toxic effects, including cancer and possibly atherosclerosis. We previously reported that PCB 126, the most potent dioxin-like PCB congener, not only decreases antioxidants such as hepatic selenium (Se), Se-dependent glutathione peroxidase, and glutathione (GSH) but also increases levels of the antiatherosclerosis enzyme paraoxonase 1 (PON1) in liver and serum. To probe the interconnection of these three antioxidant systems, Se, GSH, and PON1, we examined the influence of varying levels of dietary Se and N-acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS) and precursor for GSH synthesis, on PON1 in the absence and presence of PCB 126 exposure. Male Sprague-Dawley rats, fed diets with differing Se levels (0.02, 0.2, or 2 ppm) or NAC (1%), were treated with a single intraperitoneal injection of corn oil or various doses of PCB 126 and euthanized 2 weeks later. PCB 126 significantly increased liver PON1 mRNA, protein level and activity, and serum PON1 activity in all dietary groups but did not consistently increase thiobarbituric acid levels (thiobarbituric acid reactive substances, TBARS), an indicator of lipid oxidation and oxidative stress, in liver or serum. Inadequate (high or low) dietary Se decreased baseline and PCB 126-induced aryl hydrocarbon receptor (AhR) expression but further increased PCB 126-induced cytochrome P450 1A1 (CYP1A1) expression, the enzyme believed to be the cause for PCB 126-induced oxidative stress. In addition, a significant inverse relationship was observed not only between dietary Se levels and PON1 mRNA and PON1 activity but also with TBARS levels in the liver, suggesting significant antioxidant protection from dietary Se. NAC lowered serum baseline TBARS levels in controls and increased serum PON1 activity but lowered liver PON1 activities in animals treated with 1 μmol/kg PCB 126, suggesting

  5. Paraoxonase (PON1 55 polymorphism and association with systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Fariborz Bahrehmand

    2013-09-01

    Full Text Available Paraoxonase-1 (PON1 is a serum HDL-bound enzyme that hydrolyzes a number of aromatic carboxylic acid esters including lipid peroxides, preventing LDL oxidation. Systemic lupus erythematosus (SLE patients are at greater risk of oxidative stress, which is associated with abnormal plasma lipid metabolism. In this study, association of PON-55 polymorphism with serum arylesterase (ARE activities, malondialdehyde (MDA, neopterin, lipids and lipoproteins levels in SLE patients and the development of hypertension was investigated. The present case-control study consisted of 109 SLE patients with and without high blood pressure (BP and 103 healthy controls from the population in the west of Iran. PON-55 Met

  6. Solubilization and Humanization of Paraoxonase-1

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    Mohosin Sarkar

    2012-01-01

    Full Text Available Paraoxonase-1 (PON1 is a serum protein, the activity of which is related to susceptibility to cardiovascular disease and intoxication by organophosphorus (OP compounds. It may also be involved in innate immunity, and it is a possible lead molecule in the development of a catalytic bioscavenger of OP pesticides and nerve agents. Human PON1 expressed in E. coli is mostly found in the insoluble fraction, which motivated the engineering of soluble variants, such as G2E6, with more than 50 mutations from huPON1. We examined the effect on the solubility, activity, and stability of three sets of mutations designed to solubilize huPON1 with fewer overall changes: deletion of the N-terminal leader, polar mutations in the putative HDL binding site, and selection of the subset of residues that became more polar in going from huPON1 to G2E6. All three sets of mutations increase the solubility of huPON1; the HDL-binding mutant has the largest effect on solubility, but it also decreases the activity and stability the most. Based on the G2E6 polar mutations, we “humanized” an engineered variant of PON1 with high activity against cyclosarin (GF and found that it was still very active against GF with much greater similarity to the human sequence.

  7. The effect of in vitro dieldrin exposure on the rat paraoxonase 1 (pon1) promoter.

    Science.gov (United States)

    Dail, Mary Beth; Pickin, Rebecca; Crow, John Allen; Chambers, Janice E

    2014-05-01

    The legacy organochlorine insecticide, dieldrin, is still found in soil and accumulation in individuals is possible. Paraoxonase 1 hydrolyzes the oxon metabolites of organophosphorus insecticides, as well as other substrates. Putative binding sites for pregnane X receptor (PXR) exist in the paraoxonase promoter, and studies have indicated that dieldrin can activate PXR-regulated gene expression. We examined rat paraoxonase promoter activity in the presence of dieldrin alone or combined with nuclear receptors (NRs). In vitro dieldrin concentrations from 10 to 100 µM significantly increased (p dieldrin can increase paraoxonase promoter activity in the presence of NRs. To our knowledge, this is the first report of dieldrin increasing paraoxonase promoter activity. Since many organochlorine insecticides are in the same chemical class as dieldrin, these results could be typical of other bioaccumulative persistent pollutants. © 2014 Wiley Periodicals, Inc.

  8. Pressure effects on catalytic properties and structural stability of human paraoxonase

    Energy Technology Data Exchange (ETDEWEB)

    Clery-Barraud, C; Leva, J; Bakdouri, N E; Renault, F; Masson, P; Rochu, D [Departement de Toxicologie, Centre de Recherches du Service de Sante des Armees, BP 87, 38702 La Tronche cedex (France)], E-mail: cclerybarraud@crssa.net

    2008-07-15

    Human paraoxonase (HuPON1) is a candidate as catalytic bioscavenger for pre-treatment and therapy of poisoning by organophosphate compounds. HuPON1 is a hydrophobic protein associated with a partner, the human phosphate binding protein (HPBP) in plasma high density lipoproteins. The relationship between the composition and the size of multimeric states of HuPON1 is not well understood. Moreover the effect of HPBP's presence on enzyme catalytic mechanisms and stability is unclear. We investigated the effect of hydrostatic pressure and temperature on structural stability and activity of different PON1 preparations (hybrid recombinant PON1, natural HuPON1 free of its partner or in the presence of 50% w/w HPBP). We showed that PON1 exists under several multimeric forms and that the binding of HPBP amends the size of the hetero-oligomeric states and exerts a stabilizing effect on the activity of PON1.

  9. Pressure effects on catalytic properties and structural stability of human paraoxonase

    Science.gov (United States)

    Cléry-Barraud, C.; Leva, J.; Bakdouri, N. E.; Renault, F.; Masson, P.; Rochu, D.

    2008-07-01

    Human paraoxonase (HuPON1) is a candidate as catalytic bioscavenger for pre-treatment and therapy of poisoning by organophosphate compounds. HuPON1 is a hydrophobic protein associated with a partner, the human phosphate binding protein (HPBP) in plasma high density lipoproteins. The relationship between the composition and the size of multimeric states of HuPON1 is not well understood. Moreover the effect of HPBP's presence on enzyme catalytic mechanisms and stability is unclear. We investigated the effect of hydrostatic pressure and temperature on structural stability and activity of different PON1 preparations (hybrid recombinant PON1, natural HuPON1 free of its partner or in the presence of 50% w/w HPBP). We showed that PON1 exists under several multimeric forms and that the binding of HPBP amends the size of the hetero-oligomeric states and exerts a stabilizing effect on the activity of PON1.

  10. The Relationship between PON1 phenotype and PON1-192 genotype in detoxification of three oxons by human liver.

    Science.gov (United States)

    Mutch, Elaine; Daly, Ann K; Williams, Faith M

    2007-02-01

    Phosphorothioate pesticides (OP) such as diazinon, chlorpyrifos, and parathion are activated to highly toxic oxon metabolites by the cytochromes P450 (P450s), mainly in the liver. Simultaneously, the P450s catalyze detoxification of OP to nontoxic dearylated metabolites. The oxon is then detoxified to the dearylated metabolite by PON1, an A-esterase present in the liver and blood serum. The aims of this study were to define the influence of PON1-192 genotype and phenotype on the capacity of human liver microsomes (n = 27) to detoxify the oxons diazoxon, chlorpyrifos-oxon, and paraoxon. Near physiological assay conditions were used to reflect as closely as possible metabolism in vivo and because the hydrolytic activity of the allelic variants of PON1-192 are differentially affected by a number of conditions. The rates of hydrolysis of diazoxon, chlorpyrifos-oxon, and paraoxon varied 5.7-, 16-, and 56-fold, respectively, regardless of PON1-192 genotype. Individuals with the PON1-192RR genotype preferentially hydrolyzed paraoxon (p < 0.01), and the R allele was associated with higher hydrolytic activity toward chlorpyrifos-oxon, but not diazoxon. There were strongly significant relationships between phenylacetate and paraoxon hydrolysis (p < 0.001) and phenylacetate and chlorpyrifos-oxon hydrolysis (p < 0.001), but not between phenylacetate and diazoxon hydrolysis. These data highlight the importance of PON1 phenotype for efficient hydrolysis of paraoxon and chlorpyrifos-oxon, but environmental and yet unknown genetic factors are more important than PON1-192 genotype in determining capacity to hydrolyze diazoxon.

  11. The activity of paraoxonase type 1 (PON-1) in boar seminal plasma and its relationship with sperm quality, functionality, and in vivo fertility.

    Science.gov (United States)

    Barranco, I; Tvarijonaviciute, A; Perez-Patiño, C; Alkmin, D V; Ceron, J J; Martinez, E A; Rodriguez-Martinez, H; Roca, J

    2015-03-01

    Paraoxonase 1 (PON-1) is a hydrolytic enzyme present in body fluids, capable of protecting cells against oxidative stress. The hypothesis was hereby to test that PON-1, present in seminal plasma (SP), acts protecting boar spermatozoa when showing a reasonable high activity in the ejaculate. SP-PON-1 activity differed (p boars (from 0.10 to 0.29 IU/mL). Intra-boar variability was also observed (p boars. SP-PON-1 activity differed among ejaculate portions, showing the spermatozoa-peak portion of spermatozoa-rich ejaculate fraction the highest levels (0.35 ± 0.03 IU/mL, ranging from 0.12 to 0.69) and the post-sperm ejaculate fraction the lowest levels (0.12 ± 0.01 IU/mL, ranging from 0.03 to 0.21). SP-PON-1 activity was positively correlated with the percentage of spermatozoa with rapid and progressive movement (p boars with highest farrowing rates. In conclusion, SP-PON-1 activity differed among boars and ejaculate fractions/portions. SP-PON-1 activity was positively correlated with sperm quality and functionality of liquid-stored semen samples and it evidenced a positive association with in vivo fertility.

  12. VX Hydrolysis by Human Serum Paraoxonase 1: A Comparison of Experimental and Computational Results

    OpenAIRE

    Matthew W Peterson; Steven Z Fairchild; Otto, Tamara C.; Mojdeh Mohtashemi; Cerasoli, Douglas M.; Wenling E Chang

    2011-01-01

    Human Serum paraoxonase 1 (HuPON1) is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for this purpose. The binding interaction between HuPON1 and VX has recently been modeled, but the mech...

  13. Refolded Recombinant Human Paraoxonase 1 Variant Exhibits Prophylactic Activity Against Organophosphate Poisoning.

    Science.gov (United States)

    Bajaj, Priyanka; Tripathy, Rajan K; Aggarwal, Geetika; Datusalia, Ashok K; Sharma, Shyam S; Pande, Abhay H

    2016-09-01

    Organophosphate (OP) compounds are neurotoxic chemicals, and current treatments available for OP-poisoning are considered as unsatisfactory and inadequate. There is an urgent need for the development of more effective treatment(s) for OP-poisoning. Human paraoxonase 1 (h-PON1) is known to hydrolyze a variety of OP-compounds and is a leading candidate for the development of prophylactic and therapeutic agent against OP-poisoning in humans. Non-availability of effective system(s) for the production of recombinant h-PON1 (rh-PON1) makes it hard to produce improved variant(s) of this enzyme and analyze their in vivo efficacy in animal models. Production of recombinant h-PON1 (rh-PON1) using an Escherichia coli expression system is a key to develop variant(s) of h-PON1. Recently, we have developed a procedure to produce active rh-PON1 enzymes by using E. coli expression system. In this study, we have characterized the OP-hydrolyzing properties of refolded rh-PON1(wt) and rh-PON1(H115W;R192K) variant. Our results show that refolded rh-PON1(H115W;R192K) variant exhibit enhanced OP-hydrolyzing activity in in vitro and ex vivo assays and exhibited prophylactic activity in mouse model of OP-poisoning, suggesting that refolded rh-PON1 can be developed as a therapeutic candidate.

  14. Arylesterase activity is associated with antioxidant intake and paraoxonase-1 (PON1) gene methylation in metabolic syndrome patients following an energy restricted diet.

    Science.gov (United States)

    de la Iglesia, Rocio; Mansego, Maria L; Sánchez-Muniz, Francisco J; Zulet, M Angeles; Martinez, J Alfredo

    2014-01-01

    The arylesterase (ARE) activity linked to the paraoxonase-1 (PON1) gene is known to protect lipoproteins from oxidation and provide defense against metabolic syndrome (MetS) and cardiovascular diseases. The epigenetic regulation of enzymatic activities is gaining importance nowadays. This research aimed to assess the potential relationships between the ARE activity with the methylation levels of the PON1 gene transcriptional regulatory region, anthropometrics, biochemical markers and antioxidant dietary components. Forty-seven subjects (47 ± 10 y.o; BMI 36.2 ± 3.8 kg/m(2); 46.8 % female) with MetS features, who followed a six-month energy-restricted dietary weight-loss intervention, were included in this study (www.clinicaltrials.gov; NCT01087086). Anthropometric, biochemical, enzymatic and dietary data were assessed using validated procedures. PON1 transcriptional regulatory region methylation was analyzed by a microarray technical approach. Volunteers reduced ARE activity in parallel with body weight (p = 0.005), BMI (p = 0.006), total fat mass (p = 0.020), diastolic blood pressure (p = 0.018), mean blood pressure (p = 0.022) and triglycerides (p = 0.014). Methylation levels of some CpG sites of the PON1 gene correlated negatively with ARE activity (p < 0.05). Interestingly, dietary vitamin C (p = 0.001), tocopherols (p = 0.009) and lycopene (p = 0.038) were positively associated with ARE activity and showed an inverse correlation (p = 0.004, p = 0.029 and p = 0.021, respectively) with the methylation of some selected CpG sites of the PON1 gene. In conclusion, ARE activity decreased in parallel with MetS-related markers associated to the energy restriction, while dietary antioxidants might enhance the ARE activity by lowering the PON1 gene methylation in patients with MetS features.

  15. Insights into the Lactonase Mechanism of Serum Paraoxonase 1 (PON1): Experimental and Quantum Mechanics/Molecular Mechanics (QM/MM) Studies.

    Science.gov (United States)

    Le, Quang Anh Tuan; Kim, Seonghoon; Chang, Rakwoo; Kim, Yong Hwan

    2015-07-30

    Serum paraoxonase 1 (PON1) is a versatile enzyme for the hydrolysis of various substrates (e.g., lactones, phosphotriesters) and for the formation of a promising chemical platform γ-valerolactone. Elucidation of the PON1-catalyzed lactonase reaction mechanism is very important for understanding the enzyme function and for engineering this enzyme for specific applications. Kinetic study and hybrid quantum mechanics/molecular mechanics (QM/MM) method were used to investigate the PON1-catalyzed lactonase reaction of γ-butyrolactone (GBL) and (R)-γ-valerolactone (GVL). The activation energies obtained from the QM/MM calculations were in good agreement with the experiments. Interestingly, the QM/MM energy barriers at MP2/3-21G(d,p) level for the lactonase of GVL and GBL were respectively 14.3-16.2 and 11.5-13.1 kcal/mol, consistent with the experimental values (15.57 and 14.73 kcal/mol derived from respective kcat values of 36.62 and 147.21 s(-1)). The QM/MM energy barriers at MP2/6-31G(d) and MP2/6-31G(d,p) levels were also in relatively good agreements with the experiments. Importantly, the difference in the QM/MM energy barriers at MP2 level with all investigated basis sets for the lactonase of GVL and GBL were in excellent agreement with the experiments (0.9-3.1 and 0.8 kcal/mol, respectively). A detailed mechanism for the PON1-catalyzed lactonase reaction was also proposed in this study.

  16. Targeting paraoxonase-1 in atherosclerosis.

    Science.gov (United States)

    Mackness, Mike; Mackness, Bharti

    2013-07-01

    Paraoxonase-1 (PON1) is a Ca(2+) dependent, high-density lipoprotein-associated lactonase which is capable of retarding/inhibiting low-density lipoprotein (LDL) oxidation. LDL oxidation is believed to be central to the initiation and progression of atherosclerosis, therefore, PON1 is considered to be atheroprotective. Relevant literature on PON1 was identified in PubMed. Here, we discuss the background to research on PON1 in atherosclerosis, the evidence for and against PON1 being atheroprotective, potential mechanisms of this atheroprotection and current knowledge on human PON1 regulation. Although current knowledge on PON1 indicates it to be atheroprotective, further clinical and basic studies are warranted to show that PON1 is causally linked to atherosclerosis, how it is atheroprotective and how it is regulated in vivo in humans.

  17. Targeted Proteomics Identifies Paraoxonase/Arylesterase 1 (PON1) and Apolipoprotein Cs as Potential Risk Factors for Hypoalphalipoproteinemia in Diabetic Subjects Treated with Fenofibrate and Rosiglitazone*

    Science.gov (United States)

    Ronsein, Graziella E.; Reyes-Soffer, Gissette; He, Yi; Oda, Michael; Ginsberg, Henry; Heinecke, Jay W.

    2016-01-01

    Low levels of high-density lipoprotein cholesterol (HDL-C) and high triglyceride levels contribute to the excess rate of cardiovascular events seen in subjects with type 2 diabetes. Fenofibrate treatment partially reverses dyslipidemia in these subjects. However, a paradoxical marked reduction in HDL-C and HDL's major protein, apolipoprotein A-I, is a complication of fenofibrate in combination with rosiglitazone, an insulin-sensitizing agent. Risk factors for this condition, termed hypoalphalipoproteinemia, have yet to be identified. Using a case-control study design with subjects enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, we tested the hypothesis that alterations in HDL's protein cargo predispose diabetic subjects to fenofibrate/rosiglitazone-induced hypoalphalipoproteinemia. HDL was isolated from blood obtained from controls (no decreases or increase in HDL-C while receiving fenofibrate/rosiglitazone therapy) and cases (developed hypoalphalipoproteinemia after fenofibrate/rosiglitazone treatment) participating in the ACCORD study before they began fenofibrate/rosiglitazone treatment. HDL proteins were quantified by targeted parallel reaction monitoring (PRM) and selected reaction monitoring (SRM) with isotope dilution. This approach demonstrated marked increases in the relative concentrations of paraoxonase/arylesterase 1 (PON1), apolipoprotein C-II (APOC2), apolipoprotein C-I, and apolipoprotein H in the HDL of subjects who developed hypoalphalipoproteinemia. The case and control subjects did not differ significantly in baseline HDL-C levels or other traditional lipid risk factors. We used orthogonal biochemical techniques to confirm increased levels of PON1 and APOC2. Our observations suggest that an imbalance in HDL proteins predisposes diabetic subjects to develop hypoalphalipoproteinemia on fenofibrate/rosiglitazone therapy. PMID:26667175

  18. Efficient hydrolysis of the chemical warfare nerve agent tabun by recombinant and purified human and rabbit serum paraoxonase 1.

    Science.gov (United States)

    Valiyaveettil, Manojkumar; Alamneh, Yonas; Biggemann, Lionel; Soojhawon, Iswarduth; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2010-12-03

    Paraoxonase 1 (PON1) has been described as an efficient catalytic bioscavenger due to its ability to hydrolyze organophosphates (OPs) and chemical warfare nerve agents (CWNAs). It is the future most promising candidate as prophylactic medical countermeasure against highly toxic OPs and CWNAs. Most of the studies conducted so far have been focused on the hydrolyzing potential of PON1 against nerve agents, sarin, soman, and VX. Here, we investigated the hydrolysis of tabun by PON1 with the objective of comparing the hydrolysis potential of human and rabbit serum purified and recombinant human PON1. The hydrolysis potential of PON1 against tabun, sarin, and soman was evaluated by using an acetylcholinesterase (AChE) back-titration Ellman method. Efficient hydrolysis of tabun (100 nM) was observed with ∼25-40 mU of PON1, while higher concentration (80-250 mU) of the enzyme was required for the complete hydrolysis of sarin (11 nM) and soman (3 nM). Our data indicate that tabun hydrolysis with PON1 was ∼30-60 times and ∼200-260 times more efficient than that with sarin and soman, respectively. Moreover, the catalytic activity of PON1 varies from source to source, which also reflects their efficiency of hydrolyzing different types of nerve agents. Thus, efficient hydrolysis of tabun by PON1 suggests its promising potential as a prophylactic treatment against tabun exposure.

  19. VX hydrolysis by human serum paraoxonase 1: a comparison of experimental and computational results.

    Directory of Open Access Journals (Sweden)

    Matthew W Peterson

    Full Text Available Human Serum paraoxonase 1 (HuPON1 is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for this purpose. The binding interaction between HuPON1 and VX has recently been modeled, but the mechanism for VX hydrolysis is still unknown. In this study, we created a transition state model for VX hydrolysis (VX(ts in water using quantum mechanical/molecular mechanical simulations, and docked the transition state model to 22 experimentally characterized HuPON1 variants using AutoDock Vina. The HuPON1-VX(ts complexes were grouped by reaction mechanism using a novel clustering procedure. The average Vina interaction energies for different clusters were compared to the experimentally determined activities of HuPON1 variants to determine which computational procedures best predict how well HuPON1 variants will hydrolyze VX. The analysis showed that only conformations which have the attacking hydroxyl group of VX(ts coordinated by the sidechain oxygen of D269 have a significant correlation with experimental results. The results from this study can be used for further characterization of how HuPON1 hydrolyzes VX and design of HuPON1 variants with increased activity against VX.

  20. VX hydrolysis by human serum paraoxonase 1: a comparison of experimental and computational results.

    Science.gov (United States)

    Peterson, Matthew W; Fairchild, Steven Z; Otto, Tamara C; Mohtashemi, Mojdeh; Cerasoli, Douglas M; Chang, Wenling E

    2011-01-01

    Human Serum paraoxonase 1 (HuPON1) is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for this purpose. The binding interaction between HuPON1 and VX has recently been modeled, but the mechanism for VX hydrolysis is still unknown. In this study, we created a transition state model for VX hydrolysis (VX(ts)) in water using quantum mechanical/molecular mechanical simulations, and docked the transition state model to 22 experimentally characterized HuPON1 variants using AutoDock Vina. The HuPON1-VX(ts) complexes were grouped by reaction mechanism using a novel clustering procedure. The average Vina interaction energies for different clusters were compared to the experimentally determined activities of HuPON1 variants to determine which computational procedures best predict how well HuPON1 variants will hydrolyze VX. The analysis showed that only conformations which have the attacking hydroxyl group of VX(ts) coordinated by the sidechain oxygen of D269 have a significant correlation with experimental results. The results from this study can be used for further characterization of how HuPON1 hydrolyzes VX and design of HuPON1 variants with increased activity against VX.

  1. Computational characterization of how the VX nerve agent binds human serum paraoxonase 1.

    Science.gov (United States)

    Fairchild, Steven Z; Peterson, Matthew W; Hamza, Adel; Zhan, Chang-Guo; Cerasoli, Douglas M; Chang, Wenling E

    2011-01-01

    Human serum paraoxonase 1 (HuPON1) is an enzyme that can hydrolyze various chemical warfare nerve agents including VX. A previous study has suggested that increasing HuPON1's VX hydrolysis activity one to two orders of magnitude would make the enzyme an effective countermeasure for in vivo use against VX. This study helps facilitate further engineering of HuPON1 for enhanced VX-hydrolase activity by computationally characterizing HuPON1's tertiary structure and how HuPON1 binds VX. HuPON1's structure is first predicted through two homology modeling procedures. Docking is then performed using four separate methods, and the stability of each bound conformation is analyzed through molecular dynamics and solvated interaction energy calculations. The results show that VX's lone oxygen atom has a strong preference for forming a direct electrostatic interaction with HuPON1's active site calcium ion. Various HuPON1 residues are also detected that are in close proximity to VX and are therefore potential targets for future mutagenesis studies. These include E53, H115, N168, F222, N224, L240, D269, I291, F292, and V346. Additionally, D183 was found to have a predicted pKa near physiological pH. Given D183's location in HuPON1's active site, this residue could potentially act as a proton donor or accepter during hydrolysis. The results from the binding simulations also indicate that steered molecular dynamics can potentially be used to obtain accurate binding predictions even when starting with a closed conformation of a protein's binding or active site.

  2. Paraoxonase 2 protein is spatially expressed in the human placenta and selectively reduced in labour

    OpenAIRE

    Alwarfaly, Samy; Abdulsid, Akrem; Hanretty, Kevin; Lyall, Fiona

    2014-01-01

    Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1–3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON...

  3. Long term stability of paraoxonase-1 and high-density lipoprotein in human serum

    Directory of Open Access Journals (Sweden)

    Beekhof Piet K

    2012-05-01

    Full Text Available Abstract Background Paraoxonase-1 (PON1 is an enzyme with numerous functions and receives an increasing interest in clinical and epidemiological studies. Sometimes samples are stored for longer periods at a certain temperature. Therefore the stability of PON1 activity must be checked and retained upon storage for longer periods. Results In this study the stability of PON1 activity has been tested in human serum samples during storage up to 12 months at 3 commonly used temperatures, -20°C, -70°C and −196°C. It was found that the stability of the PON1 activity is constant during 12 months of storage at −70°C and −196°C. Storage at −20°C resulted in a small but statistically significant decrease after 6 months to about 94% of its original value. Nonetheless, the rank order between the samples at T = 0 and 12 months remained the same. The same temperature dependence was found for the associated high-density lipoprotein. Conclusions It can be concluded that −70°C is the right temperature for storage to maintain the PON1 activity for at least one year. Storage at a lower temperature in liquid nitrogen (−196°C is not necessary.

  4. Human Paraoxonase 1 as a Pharmacologic Agent: Limitations and Perspectives

    Directory of Open Access Journals (Sweden)

    Priyanka Bajaj

    2014-01-01

    Full Text Available Human PON1 (h-PON1 is a multifaceted enzyme and can hydrolyze (and inactivate a wide range of substrates. The enzyme shows anti-inflammatory, antioxidative, antiatherogenic, ant-diabetic, antimicrobial, and organophosphate (OP-detoxifying properties. However, there are certain limitations regarding large-scale production and use of h-PON1 as a therapeutic candidate. These include difficulties in producing recombinant h-PON1 (rh-PON1 using microbial expression system, low hydrolytic activity of wild-type h-PON1 towards certain substrates, and low storage stability of the purified enzyme. This review summarizes the work done in our laboratory to address these limitations. Our results show that (a optimized polynucleotide sequence encoding rh-PON1 can express the protein in an active form in E. coli and can be used to generate variant of the enzyme having enhanced hydrolytic activity, (b in vitro refolding of rh-PON1 enzyme can dramatically increase the yield of an active enzyme, (c common excipients can be used to stabilize purified rh-PON1 enzyme when stored under different storage conditions, and (d variants of rh-PON1 enzyme impart significant protection against OP-poisoning in human blood (ex vivo and mouse (in vivo model of OP-poisoning. The rh-PON1 variants and their process of production discussed here will help to develop h-PON1 as a therapeutic candidate.

  5. Serum paraoxonase 1 activity in dogs

    DEFF Research Database (Denmark)

    Rossi, Gabriele; Giordano, Alessia; Pezzia, Francesca

    2013-01-01

    Serum activity of paraoxonase (PON1) decreases during inflammation in many species. Little information is available on paraoxon-based tests and the possible role of PON1 in dogs.......Serum activity of paraoxonase (PON1) decreases during inflammation in many species. Little information is available on paraoxon-based tests and the possible role of PON1 in dogs....

  6. Human Paraoxonase-1 Activity Is Related to the Number of CD4+ T-Cells and Is Restored by Antiretroviral Therapy in HIV-1-Infected Individuals

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    Luciana Morganti Ferreira Maselli

    2014-01-01

    Full Text Available Background. Paraoxonase-1 (PON1 activity is suggested to be altered in individuals infected with human immunodeficiency virus type-1 (HIV-1. We investigated PON1 activity in individuals receiving different regimens of highly active antiretroviral therapy (HAART. Methods. PON1 activity was evaluated in 91 HIV-1 seronegative and 624 HIV-1 infected individuals (115 were not undergoing therapy (ART-naïve, and 509 were receiving HAART. HIV-1 infected individuals were treated with the following: efavirenz (EFV; n=195 or nevirapine (NVP; n=95 or lopinavir/ritonavir (LOP/r; n=219. Serum levels of total cholesterol (TC, HDL, and low-density lipoprotein (LDL fractions and the atherogenic indices (AI, TC : HDL, and LDL : HDL ratios were determined. Results. PON1 activity (U/L was lower in the ART-naïve group compared with the other groups. PON1 activity correlated with CD4+ T-cell number of ART-naïve group (r=0,121; P=0,014. The LOP/r group showed a reduction in HDL and an increase in AI (TC : HDL ratio in comparison with other groups. Conclusion. PON1 activity was reduced in untreated individuals, but not in individuals receiving HAART. PON1 activity correlated with the number of CD4+ T-cells. The findings suggest that the activity of PON1 is associated with the immune status of HIV-1 infected individuals.

  7. Towards Understanding the Catalytic Mechanism of Human Paraoxonase 1: Experimental and In Silico Mutagenesis Studies.

    Science.gov (United States)

    Tripathy, Rajan K; Aggarwal, Geetika; Bajaj, Priyanka; Kathuria, Deepika; Bharatam, Prasad V; Pande, Abhay H

    2017-02-04

    Human paraoxonase 1 (h-PON1) is a ~45-kDa serum enzyme that can hydrolyze a variety of substrates, including organophosphate (OP) compounds. It is a potential candidate for the development of antidote against OP poisoning in humans. However, insufficient OP-hydrolyzing activity of native enzyme affirms the urgent need to develop improved variant(s) having enhanced OP-hydrolyzing activity. The crystal structure of h-PON1 remains unsolved, and the molecular details of how the enzyme catalyses hydrolysis of different types of substrates are also not clear. Understanding the molecular details of the catalytic mechanism of h-PON1 is essential to engineer better variant(s) of enzyme. In this study, we have used a random mutagenesis approach to increase the OP-hydrolyzing activity of recombinant h-PON1. The mutants not only showed a 10-340-fold increased OP-hydrolyzing activity against different OP substrates but also exhibited differential lactonase and arylesterase activities. In order to investigate the mechanistic details of the effect of observed mutations on the hydrolytic activities of enzyme, molecular docking studies were performed with selected mutants. The results suggested that the observed mutations permit differential binding of substrate/inhibitor into the enzyme's active site. This may explain differential hydrolytic activities of the enzyme towards different substrates.

  8. PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Ellison, Corie A., E-mail: cellison@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Crane, Alice L., E-mail: alcrane@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Bonner, Matthew R., E-mail: mrbonner@buffalo.edu [Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Knaak, James B., E-mail: jbknaak@aol.com [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Browne, Richard W., E-mail: rwbrowne@buffalo.edu [Department of Biotechnical and Clinical Laboratory Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Lein, Pamela J., E-mail: pjlein@ucdavis.edu [Department of Molecular Biosciences, University of California School of Veterinary Medicine, Davis, CA 95618 (United States); Olson, James R., E-mail: jolson@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States)

    2012-12-15

    Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n = 120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P ≤ 0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P ≤ 0.05) and PON1 192 (P ≤ 0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal. -- Highlights: ► CPF exposure resulted in an increase in TCPy and decreases in BuChE and AChE. ► CPOase activity decreased in subjects with the PON1 55LM and PON1 55 MM genotypes. ► Neither PON1 genotype nor CPOase activity had an effect on BuChE or AChE inhibition.

  9. PON1 and Mediterranean Diet

    Science.gov (United States)

    Lou-Bonafonte, José M.; Gabás-Rivera, Clara; Navarro, María A.; Osada, Jesús

    2015-01-01

    The Mediterranean diet has been proven to be highly effective in the prevention of cardiovascular diseases. Paraoxonase 1 (PON1) has been implicated in the development of those conditions, especially atherosclerosis. The present work describes a systematic review of current evidence supporting the influence of Mediterranean diet and its constituents on this enzyme. Despite the differential response of some genetic polymorphisms, the Mediterranean diet has been shown to exert a protective action on this enzyme. Extra virgin olive oil, the main source of fat, has been particularly effective in increasing PON1 activity, an action that could be due to low saturated fatty acid intake, oleic acid enrichment of phospholipids present in high-density lipoproteins that favor the activity, and increasing hepatic PON1 mRNA and protein expressions induced by minor components present in this oil. Other Mediterranean diet constituents, such as nuts, fruits and vegetables, have been effective in modulating the activity of the enzyme, pomegranate and its compounds being the best characterized items. Ongoing research on compounds isolated from all these natural products, mainly phenolic compounds and carotenoids, indicates that some of them are particularly effective, and this may enhance the use of nutraceuticals and functional foods capable of potentiating PON1 activity. PMID:26024295

  10. PON1 and Mediterranean Diet

    Directory of Open Access Journals (Sweden)

    José M. Lou-Bonafonte

    2015-05-01

    Full Text Available The Mediterranean diet has been proven to be highly effective in the prevention of cardiovascular diseases. Paraoxonase 1 (PON1 has been implicated in the development of those conditions, especially atherosclerosis. The present work describes a systematic review of current evidence supporting the influence of Mediterranean diet and its constituents on this enzyme. Despite the differential response of some genetic polymorphisms, the Mediterranean diet has been shown to exert a protective action on this enzyme. Extra virgin olive oil, the main source of fat, has been particularly effective in increasing PON1 activity, an action that could be due to low saturated fatty acid intake, oleic acid enrichment of phospholipids present in high-density lipoproteins that favor the activity, and increasing hepatic PON1 mRNA and protein expressions induced by minor components present in this oil. Other Mediterranean diet constituents, such as nuts, fruits and vegetables, have been effective in modulating the activity of the enzyme, pomegranate and its compounds being the best characterized items. Ongoing research on compounds isolated from all these natural products, mainly phenolic compounds and carotenoids, indicates that some of them are particularly effective, and this may enhance the use of nutraceuticals and functional foods capable of potentiating PON1 activity.

  11. PON1 and Mediterranean Diet.

    Science.gov (United States)

    Lou-Bonafonte, José M; Gabás-Rivera, Clara; Navarro, María A; Osada, Jesús

    2015-05-27

    The Mediterranean diet has been proven to be highly effective in the prevention of cardiovascular diseases. Paraoxonase 1 (PON1) has been implicated in the development of those conditions, especially atherosclerosis. The present work describes a systematic review of current evidence supporting the influence of Mediterranean diet and its constituents on this enzyme. Despite the differential response of some genetic polymorphisms, the Mediterranean diet has been shown to exert a protective action on this enzyme. Extra virgin olive oil, the main source of fat, has been particularly effective in increasing PON1 activity, an action that could be due to low saturated fatty acid intake, oleic acid enrichment of phospholipids present in high-density lipoproteins that favor the activity, and increasing hepatic PON1 mRNA and protein expressions induced by minor components present in this oil. Other Mediterranean diet constituents, such as nuts, fruits and vegetables, have been effective in modulating the activity of the enzyme, pomegranate and its compounds being the best characterized items. Ongoing research on compounds isolated from all these natural products, mainly phenolic compounds and carotenoids, indicates that some of them are particularly effective, and this may enhance the use of nutraceuticals and functional foods capable of potentiating PON1 activity.

  12. Molecular dynamics simulation of human serum paraoxonase 1 in DPPC bilayer reveals a critical role of transmembrane helix H1 for HDL association.

    Science.gov (United States)

    Patra, Mahesh Chandra; Rath, Surya Narayan; Pradhan, Sukanta Kumar; Maharana, Jitendra; De, Sachinandan

    2014-01-01

    Serum paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-bound mammalian enzyme exhibiting antiatherosclerotic activity. Despite years of research, an accurate model for the binding interaction between PON1 and HDL has not been established. However, it is reported that anchoring of PON1 to HDL is mainly governed by an N-terminal alpha helix H1 and another short helix H2. Here, we studied the molecular association of full-length human PON1 (huPON1) with a HDL-mimetic dipalmitoylphosphatidylcholine (DPPC) bilayer using homology modeling and molecular dynamics simulations. Our results indicate that H1 is the highly dynamic part of huPON1, showing clockwise rotation of up to 30° within the DPPC bilayer. However, without phospholipid molecules, H1 experiences helical distortions, illustrating an incompatible HDL-anchoring conformation. Snorkeling interactions of K3, R18, and R27 together with aromatic locks formed by Y187, Y190, W194, and W202 are highly essential for anchoring of huPON1 to HDL's surface. Molecular mechanics/Poisson-Boltzmann solvent-accessible surface area (MM/PBSA) binding free energy calculation revealed that H1 displays greater binding affinity towards lipid molecules compared with H2 and H3, suggesting that H1 is the most probable HDL-binding domain of PON1. Binding free energy decomposition showed that K3, R18, and R27 interact with polar headgroups of DPPC membrane through electrostatic interaction. Moreover, Y187, Y190, W194, and W202 interact with DPPC lipids mainly through van der Waals interaction. Taken together, these results show that the transmembrane helix H1 along with the interfacial positively charged and aromatic resides were crucial for PON1's association with HDL particle. The current study will be useful towards understanding the antiatherosclerotic and bioscavenging properties of this promiscuous enzyme.

  13. Relationship of PON1 192 and 55 gene polymorphisms to calcific valvular aortic stenosis

    DEFF Research Database (Denmark)

    Moura, Luis M; Faria, Susana; Brito, Miguel

    2012-01-01

    Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation. Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical and pathophy......Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation. Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical...... and pathophysiological risk factors of CAD and calcific aortic valve stenosis (CAVS), we postulated a link between PON1 alleles and CAVS progression....

  14. Polymorphisms in the genes of citohrom oxidase P450 2D6 (CYP2D6, paraoxonase 1 (PON1 and apolipoproteine E (APOE as risk factors for Parkinson's disease

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    Đurić Gordana

    2007-01-01

    Full Text Available Background/Aim. The presence of Parkinson's disease (PD among the members of a family is a clear indication of the significance of genetics in its development. In spite of that, the majority of patients with PD shows a sporadic form of the disease induced as a result of interaction of both environmental and genetic factors. The aim of this study was to examine the effects of polymorphisms in the genes of cytohrome P450 2D6(CYP2D6, paraoxonase 1 (PON 1 and apolipoprotein E (APOE, as risk factors for PD. Methods. We examined 106 patients with PD (65 men and 41 women and 75 ethnically matched control subjects. The mean age at onset of PD in the patients was 46.9±9.4 years (ranging from 30 to 70 years. Genotyping was performed using standard PCR amplification and restriction endonuclease digestion protocols described for known polymorphism in the candidate genes under study. Results. The genotype A/A polymorphisms 2D6* gene of CYP2D6 and genotype M/M polymorphisms L54M gene of PON1 were significantly more frequent in the patients with PD than in the control group. The patients with genotypes A/A and M/M had 3.4 and 3.2 higher risk of PD, respectively than the control group (p = 0.01. The relation between genotypes A/A gene of CYP2D6 and M/M gene of PON1 was modified by the age at onset. The genotypes were associated with early onset of PD (p = 0.001, p = 0.004. The carriers of the A and M alleles in homozygote had 2.4 and 4.2 years respectively earlier onset of PD than carriers of other genotypes with these polymorphisms. The frequency allele ε4 gene of APOE was higher in the PD patients with early onset (20% than in PD with later onset (7.4%, while the genotype ε3/ε3 was associated with PD late onset (p = 0.024. Combined genotype I (carriers of the two risk allels in homozygote and one alleles risk in heterozygote and combined genotype II (carriers of the three alleles risk in homozygote caused early PD. Combined genotype II was detected in 12

  15. The rs662 polymorphism of paraoxonase 1 affects the difference in the inhibition of butyrylcholinesterase activity by organophosphorus pesticides in human blood.

    Science.gov (United States)

    Nam, Dae Cheol; Ha, Yu Mi; Park, Min Kyu; Cho, Sung Kweon

    2016-08-01

    Organophosphorus pesticides (OPs) are a human health hazard. OPs inhibit acetylcholinesterase (AChE) at nerve endings and accumulate acetylcholine (ACh) at these sites. High levels of ACh and long exposure promote cholinergic crisis. The hydrolysis of OPs by serum paraoxonase 1 (PON1) plays a role in cholinergic crisis in humans. Human serum PON1 can break down organophosphate before binding to ChE. We investigated the effect of PON1 polymorphisms on AChE activity after OP treatment. 50 healthy volunteers were randomly recruited with informed consent. We investigated butyrylcholinesterase (BuChE) activity changes in plasma as a biomarker of AChE after OP treatment in human blood samples immediately following blood sampling. After the standardization of BuChE activity in human blood, we correlated changes in BuChE activity with changes in blood pH. We analyzed the PON1 polymorphisms (rs854560 and rs662) of 50 participants to retrospectively investigate the interindividual variability of changes in BuChE activity. Changes in BuChE activity are strongly correlated with pH changes after OP treatment (R2 = 0.913). We used changes in pH as a surrogate marker for BuChE inhibition after OP treatment. OP treatment significantly decreased BuChE activity by 56.4 ± 5.1% (p < 0.001). The degree of BuChE inhibition was significantly different in the PON1 rs662 genotype (56.10 ± 4.74% vs. 57.96 ± 5.67% vs. 52.34 ± 1.51%; GG vs. GA vs. AA, respectively). Changes in pH can be used as a surrogate marker for the detection of BuChE inhibition after OP exposure. The rs662 polymorphism of PON1 may explain the inter-individual variability in BuChE inhibition.

  16. Expression and purification of biologically active recombinant human paraoxonase 1 from inclusion bodies of Escherichia coli.

    Science.gov (United States)

    Bajaj, Priyanka; Tripathy, Rajan K; Aggarwal, Geetika; Pande, Abhay H

    2015-11-01

    Human PON1 (h-PON1) is a Ca(2+)-dependent serum enzyme and can hydrolyze (and inactivate) a wide range of substrates. It is a multifaceted enzyme and exhibit anti-inflammatory, anti-oxidative, anti-atherogenic, anti-diabetic, anti-microbial, and organophosphate (OP)-detoxifying properties. Thus, h-PON1 is a strong candidate for the development of therapeutic intervention against these conditions in humans. Insufficient hydrolyzing activity of native h-PON1 against desirable substrate affirms the urgent need to develop improved variant(s) of h-PON1 having enhanced activity. Production of recombinant h-PON1 (rh-PON1) using an Escherichia coli expression system is a key to develop such variant(s). However, generation of rh-PON1 using E. coli expression system has been elusive until now because of the aggregation of over-expressed rh-PON1 protein in inactive form as inclusion bodies (IBs) in the bacterial cells. In this study, we have over-expressed rh-PON1(wt) and rh-PON1(H115W;R192K) proteins as IBs in E. coli, and refolded the inactive enzymes present in the IBs to their active form using in vitro refolding. The active enzymes were isolated from the refolding mixture by ion-exchange chromatography. The catalytic properties of the refolded enzymes were similar to their soluble counterparts. Our results show that the pure and the active variant of rh-PON1 enzyme having enhanced hydrolyzing activity can be produced in large quantities using E. coli expression system. This method can be used for the industrial scale production of rh-PON1 enzymes and will aid in developing h-PON1 as a therapeutic candidate.

  17. Paraoxonase-1 genetic polymorphisms and susceptibility to DNA damage in workers occupationally exposed to organophosphate pesticides.

    Science.gov (United States)

    Singh, Satyender; Kumar, Vivek; Thakur, Sachin; Banerjee, Basu Dev; Rautela, Rajender Singh; Grover, Shyam Sunder; Rawat, Devendra Singh; Pasha, Syed Tazeen; Jain, Sudhir Kumar; Ichhpujani, Rattan Lal; Rai, Arvind

    2011-04-15

    Human paraoxonase 1 (PON1) is a lipoprotein-associated enzyme involved in the detoxification of organophosphate pesticides (OPs) by hydrolyzing the bioactive oxons. Polymorphisms of the PON1 gene are responsible for variation in the expression and catalytic activity of PON1 enzyme. In the present study, we have determined (a) the prevalence of two common PON1 polymorphisms, (b) the activity of PON1 and acetylcholinesterase enzymes, and (c) the influence of PON1 genotypes and phenotypes variation on DNA damage in workers exposed to OPs. We examined 230 subjects including 115 workers exposed to OPs and an equal number of normal healthy controls. The results revealed that PON1 activity toward paraoxon (179.19±39.36 vs. 241.52±42.32nmol/min/ml in controls) and phenylacetate (112.74±17.37 vs. 134.28±25.49μmol/min/ml in controls) was significantly lower in workers than in control subjects (p0.05). The PON1 activity toward paraoxonase was found to be significantly higher in the R/R (Arg/Arg) genotypes than Q/R (Gln/Arg) and lowest in Q/Q (Gln/Gln) genotypes in both workers and control subjects (p<0.001). For PON1(55)LM (Leu/Met), PON1 activity toward paraoxonase was observed to be higher in individuals with L/L (Leu/Leu) genotypes and lowest in individuals with M/M (Met/Met) genotypes in both groups (p<0.001). No influence of PON1 genotypes and phenotypes was seen on the activity of acetylcholinesterase and arylesterase. The DNA damage was observed to be significantly higher in workers than in control subjects (p<0.05). Further, the individuals who showed least paraoxonase activity i.e., those with (Q/Q [Gln/Gln] and M/M [Met/Met]) genotypes showed significantly higher DNA damage compared to other isoforms in workers exposed to OPs (p<0.05). The results indicate that the individuals with PON1 Q/Q and M/M genotypes are more susceptible toward genotoxicity. In conclusion, the study suggests wide variation in enzyme activities and DNA damage due to polymorphisms in PON1

  18. SERUM PARAOXONASE ACTIVITY AND ITS RELATION TO SERUM LIPIDS IN CORONARY ARTERY DISEASE

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    Rakhi S

    2015-10-01

    Full Text Available Human serum paraoxonase1 (PON1 is a calcium dependent es terase enzyme that hydrolyses lipid peroxides accumulating on low density lipoproteins. In the serum, PON1 enzyme is almost exclusively located on the high density lipoprotein (HDL. It hydrolyses oxidised lipids in low density lipoprotein (LDL and could therefore retard the development of atherosclerosis. As PON1 activity has a role in preventing atherosclerosis and coronary heart disease is common in Kerala, this study was conducted to assess the activity of the enzyme and its corelation to serum lipids. MATERIALS AND METHODS : In this case - control study, one hundred patients with coronary artery disease and one hundred healthy controls were included. Serum paraoxonase activity was meausured using phenyl acetate as substrate and lipid profile was done in a uto analyzer . RESULTS : The mean PON 1 activity {(70.21  27.62 in cases against (135.86  33.48 in controls (p value .000} was significantly low in CAD group compared to the control group. The CHD group had a significantly lower mean total cholesterol level (202.82  57.77 against 219.45  46.08 and lower mean HDL level (40.88  10.08 against 56.79  17.24. Correlation of the activity of PON1 with other variables for the combined group ( C ases and controls taken together showed that age is negatively correlated an d HDL is positively correlated with PON 1 activity. CONCLUSIONS : The activity of serum paraoxonase enzyme (PON1 is low in patients with coronary artery disease compared to healthy controls. Thus low serum PON1 enzyme activity is a risk factor for CAD. The activity of the serum PON1 enzyme increases with increase in HDL level and decreases with increase in age for the combined group.

  19. Paraoxonase 1: genetics and activities during aging.

    Science.gov (United States)

    Marchegiani, Francesca; Marra, Maurizio; Olivieri, Fabiola; Cardelli, Maurizio; James, Richard W; Boemi, Massimo; Franceschi, Claudio

    2008-02-01

    The increasing longevity of the population, one of the most important issues throughout the planet, is a very complex phenomenon (trait), likely resulting from a variety of environmental determinants interacting with and modulated by genetic mechanisms, mostly devoted to maintenance and repair. In fact, the genes involved in longevity impact upon basic processes such as inflammation, glucose and energy utilization, and oxidative stress. Based on the free radical theory of aging, in the past few years we have focused our attention on an enzyme that protects lipids from peroxidative damage-paraoxonase 1 (PON1). PON1 has been widely investigated, especially for its involvement in atherosclerosis and age-related diseases. In this review, we summarize data on the role played by PON1 on aging and its possible involvement in human longevity, focusing on the relationship between genetic polymorphisms and enzyme activity and its capability to counteract oxidative stress.

  20. The effect of HDL-bound and free PON1 on copper-induced LDL oxidation.

    Science.gov (United States)

    Bayrak, Ahmet; Bayrak, Tülin; Bodur, Ebru; Kılınç, Kamer; Demirpençe, Ediz

    2016-09-25

    Oxidative modification of LDL plays an important role in the development of atherosclerosis. High-density lipoprotein (HDL) confers protection against atherosclerosis and the antioxidative properties of paraoxonase 1 (PON1) has been suggested to contribute to this effect of HDL. The PON1 exist in two major polymorphic forms (Q and R), which regulate the concentration and activity of the enzyme and alter its ability to prevent lipid oxidation. However, the association of Q192R polymorphism with PON1's capacity to protect against LDL lipoperoxidation is controversial. The aim of this study was to evaluate the effects of the purified PON1 Q192R and the partially purified HDL-bound PON1 Q192R isoenzymes (HDL-PON1 Q192R) on LDL oxidation, with respect to their arylesterase/homocysteine thiolactonase (HTLase) activities. Cupric ion-induced LDL oxidation was reduced up to 48% by purified PON1 Q192, but only 33% by an equivalent activity of PON1 R192. HDL-PON1 Q192 isoenzyme caused a 65% reduction, whereas HDL-PON1 R192 isoenzyme caused only 46% reduction in copper ion-induced LDL oxidation. These findings reflect the fact that PON1 Q and PON1 R allozymes may have different protective characteristics against LDL oxidation. The protection against LDL oxidation provided by HDL-PON1 Q192R isoenzymes is more prominent than the purified soluble enzymes. Inhibition of the Ca(+2)-dependent PON1 Q192R arylesterase/HTLase by the metal chelator EDTA, did not alter PON1's ability to inhibit LDL oxidation. These studies indicate that the active site involvement of the purified enzyme is not similar to the HDL-bound one, in terms of both PON1 arylesterase/HTLase activity and the protection of LDL from copper ion-induced oxidation. Moreover, PON1's ability to protect LDL from oxidation does not seem to require calcium.

  1. Paraoxonase 1-192Q allele is a risk factor for idiopathic chronic pancreatitis.

    NARCIS (Netherlands)

    Verlaan, M.; Harbers, E.G.; Pap, A.; Jansen, J.B.M.J.; Peters, W.H.M.; Drenth, J.P.H.

    2005-01-01

    BACKGROUND: The cause of chronic pancreatitis (CP) remains unknown. However, oxidative stress might play a role since recent animal studies have demonstrated that oxygen-free radicals contribute to the pathogenesis of experimental pancreatitis. Human serum paraoxonase (PON1) is an antioxidant enzyme

  2. Paraoxonase 1 phenotype and paraoxonase activity in asthmatic patients.

    Directory of Open Access Journals (Sweden)

    Nurhan Sarioglu

    2015-02-01

    Full Text Available Oxidative stress is involved in the pathogenesis of asthma. Paraoxonase 1 (PON1 and arylesterase are esterase enzymes displaying antioxidant characteristics. PON1 activity varies widely among individuals and ethnic groups, partly related to polymorphisms. The aim of this study was to determine the activities of PON1 and arylesterase including the phenotype distribution of PON1 in asthmatic patients and healthy subjects. Forty-nine asthmatic patients and 41 healthy people were included in this study. Serum PON1 and arylesterase activities were determined by spectrophotometric assays, as well as the lipid profiles. The PON1 ratio (salt stimulated paraoxonase/arylesterase was trimodally distributed and this ratio was used to determine the individual phenotypes of all subjects. The PON1 activity in the asthmatic patients was significantly lower (p=0.024 when compared to the healthy control group, however no significant difference in the activity of arylesterase was observed between the two groups. The prevalence of the PON1 phenotypes in the asthmatic population were 26.5%, 16.3% and 57.2 % for QQ, QR and RR, respectively. PON1 activity was significantly lower in asthmatic patients; in addition, the results of this investigation indicated that PON1 RR phenotype may be an important risk factor in asthma disease.

  3. PON1 is a longevity gene: results of a meta-analysis.

    Science.gov (United States)

    Lescai, Francesco; Marchegiani, Francesca; Franceschi, Claudio

    2009-10-01

    Paraoxonase 1 (PON1) is one of the most studied genes regarding cardiovascular risk, oxidative stress and inflammation. Several lines of evidence suggests that PON1 promotes an atheroprotective effect. Patients carrying PON1 codon 192 QQ genotype display a higher risk of cardiovascular events, the major cause of mortality in the elderly: it can be predicted that gene variants increasing the risk of mortality will be under-represented in long-living individuals. We first reported that PON1 R allele (R+) carriers are significantly more represented in Italian centenarians; subsequently this topic has been addressed by many other groups, and here we report a meta-analysis on 11 studies in different populations selected by a review of the literature available in PubMed and testing the effect of the Q192R polymorphism on human ageing. QUORUM guidelines for meta-analysis have been followed, and a total number of 5962 subjects have been included: 2795 young controls (65 years of age). The Mantel-Haenszel weighting for pooling in presence of a fixed effects model has been applied. The meta-analysis of R carriers showed a significant result with an overall OR of 1.16 (1.04-1.30, 95% CI, p=0.006). The meta-analysis of QR genotype also showed a significant result, with an overall OR of 1.14 (1.02-1.27, 95% CI, p=0.016). The results show that PON1 gene variants at codon 192 impact on the probability of attaining longevity, and that subjects carrying RR and QR genotypes (R+ carriers) are favoured in reaching extreme ages. These results likely represent the counterpart of the effects observed on cardiovascular diseases (CVD), as centenarians and nonagenarians escaped or delayed the onset of the major age-related diseases, including CVD.

  4. Distribution profile of paraoxonase phenotypes among the Gujaratis

    Directory of Open Access Journals (Sweden)

    Patel A

    2007-01-01

    Full Text Available Background: Paraoxonase (PON1 can hydrolyze organophosphate pesticides (OP and has a key role in the susceptibility of human in OP toxicity. The human-enzyme shows polymorphism and variations in the distribution profile of its phenotypes among different ethnic groups have been observed. Aims: To see the distribution pattern of total PON1 activity in 45 healthy attendants of poisoning cases; 121 healthy unrelated farm-labours and 59 normal subjects of trauma. Materials and Methods: The PON1 activities from serum/plasma samples of these healthy normal individuals were estimated with/without addition of 1M NaCl in order to determine salt-stimulated and basal activity. The PON 1 phenotypes were determined on the basis of percent activation of enzyme activity. Results: Tri-modal distribution of basal PON1 activity was observed among all these individuals. 52.0% of the individuals belonged to Phenotype A, 46.6% to phenotype AB while 1.4% to Phenotype B with gene frequency of allele-A and allele-B being 0.753 and 0.247 respectively in excellent agreement with Hardy-Weinberg equilibrium. Conclusion: Maximum number of individuals belonged to phenotype-A (low PON1 activity showing potential vulnerability towards Op-poisoning.

  5. Human paraoxonase gene cluster overexpression alleviates angiotensin II-induced cardiac hypertrophy in mice.

    Science.gov (United States)

    Pei, Jian-Fei; Yan, Yun-Fei; Tang, Xiaoqiang; Zhang, Yang; Cui, Shen-Shen; Zhang, Zhu-Qin; Chen, Hou-Zao; Liu, De-Pei

    2016-11-01

    Cardiac hypertrophy is the strongest predictor of the development of heart failure, and anti-hypertrophic treatment holds the key to improving the clinical syndrome and increasing the survival rates for heart failure. The paraoxonase (PON) gene cluster (PC) protects against atherosclerosis and coronary artery diseases. However, the role of PC in the heart is largely unknown. To evaluate the roles of PC in cardiac hypertrophy, transgenic mice carrying the intact human PON1, PON2, and PON3 genes and their flanking sequences were studied. We demonstrated that the PC transgene (PC-Tg) protected mice from cardiac hypertrophy induced by Ang II; these mice had reduced heart weight/body weight ratios, decreased left ventricular wall thicknesses and increased fractional shortening compared with wild-type (WT) control. The same protective tendency was also observed with an Apoe (-/-) background. Mechanically, PC-Tg normalized the disequilibrium of matrix metalloproteinases (MMPs)/tissue inhibitors of MMPs (TIMPs) in hypertrophic hearts, which might contribute to the protective role of PC-Tg in cardiac fibrosis and, thus, protect against cardiac remodeling. Taken together, our results identify a novel anti-hypertrophic role for the PON gene cluster, suggesting a possible strategy for the treatment of cardiac hypertrophy through elevating the levels of the PON gene family.

  6. Interleukin-6 upregulates paraoxonase 1 gene expression via an AKT/NF-κB-dependent pathway

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Chi-Chih [Department of Research, Taichung Veterans General Hospital, Taichung, Taiwan (China); Hsueh, Chi-Mei [Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chen, Chiu-Yuan [Graduate Institute of Natural Healing Sciences, Nanhua University, Chiayi, Taiwan (China); Chen, Tzu-Hsiu, E-mail: hsiu@mail.chna.edu.tw [Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan (China); Hsu, Shih-Lan, E-mail: h2326@vghtc.gov.tw [Department of Research, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Applied Chemistry, National Chi Nan University, Puli, Nantou, Taiwan (China)

    2013-07-19

    Highlights: •IL-6 could induce PON1 gene expression. •IL-6 increased NF-κB protein expression and NF-κB-p50 and -p65 subunits nuclear translocation. •IL-6-induced PON1 up-regulation was through an AKT/NF-κB pathway. -- Abstract: The aim of this study is to investigate the relationship between paraoxonase 1 (PON1) and atherosclerosis-related inflammation. In this study, human hepatoma HepG2 cell line was used as a hepatocyte model to examine the effects of the pro-inflammatory cytokines on PON1 expression. The results showed that IL-6, but not TNF-α and IL-1β, significantly increased both the function and protein level of PON1; data from real-time RT-PCR analysis revealed that the IL-6-induced PON1 expression occurred at the transcriptional level. Increase of IκB kinase activity and IκB phosphorylation, and reduction of IκB protein level were also observed in IL-6-treated HepG2 cells compared with untreated culture. This event was accompanied by increase of NF-κB-p50 and -p65 nuclear translocation. Moreover, treatment with IL-6 augmented the DNA binding activity of NF-κB. Furthermore, pharmacological inhibition of NF-κB activation by PDTC and BAY 11-7082, markedly suppressed the IL-6-mediated PON1 expression. In addition, IL-6 increased the levels of phosphorylated protein kinase B (PKB, AKT). An AKT inhibitor LY294002 effectively suppressed IKK/IκB/NF-κB signaling and PON1 gene expression induced by IL-6. Our findings demonstrate that IL-6 upregulates PON1 gene expression through an AKT/NF-κB signaling axis in human hepatocyte-derived HepG2 cell line.

  7. Both Paraoxonase-1 Genotype and Activity Do Not Predict the Risk of Future Coronary Artery Disease; the EPIC-Norfolk Prospective Population Study

    NARCIS (Netherlands)

    R.S. Birjmohun; M. Vergeer; E.S.G. Stroes; M.S. Sandhu; S.L. Ricketts; M.W. Tanck; N.J. Wareham; J.W. Jukema; J.J.P. Kastelein; K.T. Khaw; S.M. Boekholdt

    2009-01-01

    Paraoxonase-1 (PON1) is an antioxidant enzyme, that resides on high-density lipoprotein (HDL). PON1-activity, is heavily influenced by the PON1-Q192R polymorphism. PON1 is considered to protect against atherosclerosis, but it is unclear whether this relation is independent of its carrier, HDL. In or

  8. Methodological constraints in interpreting serum paraoxonase-1 activity measurements: an example from a study in HIV-infected patients

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    Joven Jorge

    2010-03-01

    Full Text Available Abstract Background Paraoxonase-1 (PON1 is an antioxidant enzyme that attenuates the production of the monocyte chemoattractant protein-1 (MCP-1 in vitro. Although oxidation and inflammation are closely related processes, the association between PON1 and MCP-1 has not been completely characterised due, probably, to that the current use of synthetic substrates for PON1 measurement limits the interpretation of the data. In the present study, we explored the relationships between the circulating levels of PON1 and MCP-1 in human immunodeficiency virus-infected patients in relation to the multifunctional capabilities of PON1. Methods We measured selected variables in 227 patients and in a control group of 409 participants. Serum PON1 esterase and lactonase activities were measured as the rates of hydrolysis of paraoxon and of 5-(thiobutyl-butyrolactone, respectively. Oxidised LDL and MCP-1 concentrations were determined by enzyme-linked immunosorbent assay. High-density lipoproteins cholesterol, apolipoprotein A-I, and C-reactive protein concentrations were measured by standard automated methods. Results There were significant relationships between PON1 activity and several indices of oxidation and inflammation in control subjects and in infected patients. However, these relationships varied not only with disease status but also on the type of substrate used for PON1 measurement. Conclusion The present study is a cautionary tale highlighting that results of clinical studies on PON1 may vary depending on the methods used as well as the disease studied. Until more specific methods using physiologically-akin substrates are developed for PON1 measurement, we suggest the simultaneous employment of at least two different substrates in order to improve the reliability of the results obtained.

  9. Lower Serum Paraoxonase-1 Activity Is Related to Higher Serum Amyloid A Levels in Metabolic Syndrome

    NARCIS (Netherlands)

    Kappelle, Paul Jan Willem Herman; Bijzet, Johan; Hazenberg, Bouke Pier; Dullaart, Robin Pieter Frank

    Background and Aims. High-density lipoproteins (HDL) contain the anti-oxidative enzyme, paraoxonase-1 (PON-1), which is important for atheroprotection. The acute phase reactant, serum amyloid A (SAA), an HDL-associated apolipoprotein, may impair PON-1 activity, whereas SAA and PON-1 are reciprocally

  10. The positive relationship of serum paraoxonase-1 activity with apolipoprotein E is abrogated in metabolic syndrome

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Kwakernaak, Arjan J.; Dallinga-Thie, Geesje M.

    Background: High density lipoproteins (HDL) contain paraoxonase-1 (PON-1), which has strong anti-oxidative properties. Apolipoprotein E (apoE) may enhance PON-1 activity in vitro, but the extent to which PON-1 activity is determined by circulating apoE levels is unknown. Here we determined

  11. Lower Serum Paraoxonase-1 Activity Is Related to Higher Serum Amyloid A Levels in Metabolic Syndrome

    NARCIS (Netherlands)

    Kappelle, Paul Jan Willem Herman; Bijzet, Johan; Hazenberg, Bouke Pier; Dullaart, Robin Pieter Frank

    2011-01-01

    Background and Aims. High-density lipoproteins (HDL) contain the anti-oxidative enzyme, paraoxonase-1 (PON-1), which is important for atheroprotection. The acute phase reactant, serum amyloid A (SAA), an HDL-associated apolipoprotein, may impair PON-1 activity, whereas SAA and PON-1 are reciprocally

  12. Quantitative assessment of the influence of paraoxonase 1 activity and coronary heart disease risk.

    Science.gov (United States)

    Wang, Mingsong; Lang, Xilong; Cui, Shitao; Zou, Liangjian; Cao, Jia; Wang, Sheng; Wu, Xintian

    2012-06-01

    Human paraoxonase 1 (PON1) is a calcium-dependent high-density lipoprotein associated ester hydrolase that has attracted considerable attention as a candidate factor for coronary heart disease (CHD) based on its function as a key factor in lipoprotein catabolism pathways. This meta-analysis aimed to clarify the inconsistency of published studies and to establish a comprehensive picture of the relationship between PON1 activity and CHD susceptibility. A systematic search was performed from PubMed, Web of Science, EMBASE, and CNKI databases. Ratio of means (RoM) between case and control and 95% confidence intervals (CIs) were calculated using a random-effects model. The source of heterogeneity was explored by subgroup analysis and meta-regression. We identified 47 eligible studies including a total of 9853 CHD cases and 11,408 controls. The pooled analysis showed that CHD patients had a 19% lower PON1 activity than did the controls (RoM=0.81; 95% CI: 0.74-0.89, pPON1 activity associated with CHD risk was observed in almost all subgroup analysis according to ethnicity, sample size, study design, mean age of cases, source, and type of control. Decreased PON1 activity may act as a risk factor for the development of CHD. Progressive decrease in serum PON1 activity may exist for an individual with severe disease. However, larger studies using a prospective approach are needed to confirm our results.

  13. Serum paraoxonase 1 activity status in patients with liver disorders

    OpenAIRE

    Kedage Vivekananda; Muttigi Manjunatha; Shetty Mahesh; Suvarna Renuka; Rao Soumya; Joshi Chitralekha; Prakash Mungli

    2010-01-01

    Background/Aim: Paraoxonase 1 (PON1) is an esterase, exclusively synthesized by liver. The present study has two objectives: to determine the PON1 activity status in various disorders associated with hepatocellular damage and to correlate the changes of PON1 activity with the standard liver function and fasting lipid profile tests in these disorders. Patients and Methods: The study groups consisted of 95 patients with liver diseases including acute viral hepatitis (14), cirrhosis with port...

  14. Recent progress in the genetics and epigenetics of paraoxonase: why it is relevant to children’s environmental health

    Science.gov (United States)

    Holland, N; Lizarraga, D; Huen, K

    2015-01-01

    Purpose of review Children are more susceptible to exposures in utero and during early childhood that may result in developmental problems and chronic diseases. Novel discoveries in the field of molecular epidemiology which can help explain susceptibility to exposures and disease will be demonstrated using the multifunctional enzyme paraoxonase (PON1) as an example. Recent findings The broad PON1 variability in humans, partly due to differences in genetics and age, can confer differential susceptibility because this enzyme can detoxify organophosphate pesticides and has antioxidant properties. Epigenetics plays a significant role in the mediation of the effects of environmental exposure on human health and is hypothesized to be a major contributing factor to the early-life origins of adult disease. Studies highlighted in this review demonstrate the relationship of PON1 polymorphisms with microRNA binding in addition to a link between DNA methylation in the transcriptional regulatory region with changes in PON1 enzyme levels. Other important methodologies such as ancestry informative markers and lactonase activity can enhance studies involving PON1. Summary This PON1 model demonstrates that integrating genetic and epigenetic factors as well as other novel methodologies can improve our understanding of important susceptibility factors linked to pediatric disease. PMID:25635583

  15. Paraoxonase 2 protein is spatially expressed in the human placenta and selectively reduced in labour.

    Science.gov (United States)

    Alwarfaly, Samy; Abdulsid, Akrem; Hanretty, Kevin; Lyall, Fiona

    2014-01-01

    Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1-3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON2 expression would alter during labour. PON2 was examined in placentas obtained from women who delivered by cesarean section and were not in labour and compared to the equivalent zone of placentas obtained from women who delivered vaginally following an uncomplicated labour. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. PON2 expression was investigated by Western blotting and real time PCR. Two PON2 forms, one at 62 kDa and one at 43 kDa were found in all samples. No difference in protein expression of either isoform was found between the three sites in either the labour or non-labour group. At the middle site there was a highly significant decrease in PON2 expression in the labour group when compared to the non-labour group for both the 62 kDa form (p = 0.02) and the 43 kDa form (p = 0.006). No spatial differences were found within placentas at the mRNA level in either labour or non-labour. There was, paradoxically, an increase in PON2 mRNA in the labour group at the middle site only. This is the first report to describe changes in PON2 in the placenta in labour. The physiological and pathological significance of these remains to be elucidated but since PON2 is anti-inflammatory further studies are warranted to understand its role.

  16. Paraoxonase 1 polymorphism Q192R affects the pro-inflammatory cytokine TNF-alpha in healthy males

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    Rimbach Gerald

    2011-05-01

    Full Text Available Abstract Background Human paraoxonase 1 (PON1 is an HDL-associated enzyme with anti-oxidant/anti-inflammatory properties that has been suggested to play an important protective role against coronary heart diseases and underlying atherogenesis. The common PON1 Q192R polymorphism (rs662, A>G, a glutamine to arginine substitution at amino acid residue 192, has been analyzed in numerous association studies as a genetic marker for coronary heart diseases, however, with controversial results. Findings To get a better understanding about the pathophysiological function of PON1, we analyzed the relationships between the Q192R polymorphism, serum paraoxonase activity and serum biomarkers important for atherogenesis. Genotyping a cohort of 49 healthy German males for the Q192R polymorphism revealed an allele distribution of 0.74 and 0.26 for the Q and R allele, respectively, typical for Caucasian populations. Presence of the R192 allele was found to be associated with a significantly increased paraoxonase enzyme activity of 187.8 ± 11.4 U/l in comparison to the QQ192 genotype with 60.5 ± 4.9 U/l. No significant differences among the genotypes were found for blood pressure, asymmetric dimethylarginine, LDL, HDL, triglycerides, and cholesterol. As expected, MIP-2 alpha a cytokine rather not related to atherosclerosis is not affected by the PON1 polymorphism. In contrast to that, the pro-inflammatory cytokine TNF-alpha is enhanced in R192 carriers (163.8 ± 24.7 pg/ml vs 94.7 ± 3.2 pg/ml in QQ192 carriers. Conclusions Our findings support the hypothesis that the common PON1 R192 allele may be a genetic risk factor for atherogenesis by inducing chronic low-grade inflammation.

  17. Extra-virgin olive oil consumption reduces the age-related decrease in HDL and paraoxonase 1 anti-inflammatory activities.

    Science.gov (United States)

    Loued, Soumaya; Berrougui, Hicham; Componova, Pamela; Ikhlef, Souad; Helal, Olfa; Khalil, Abdelouahed

    2013-10-01

    Paraoxonase 1 (PON1) is associated with HDL and modulates the antioxidant and anti-inflammatory role of HDL. The goals of the present study were to investigate the effect of ageing and the role of PON1 on the anti-inflammatory activity of HDL, and to determine whether extra-virgin olive oil (EVOO) consumption could improve the atheroprotective activity of HDL. HDL and PON1 were isolated from the plasma of ten young (Y-HDL and Y-PON1) and ten elderly (E-HDL and E-PON1) healthy volunteers before and after 12 weeks of EVOO consumption. Inflammation was assessed by measuring intracellular adhesion molecule 1 (ICAM-1) expression. THP-1 (human acute monocytic leukaemia cell line) monocyte chemotaxis was measured using a Boyden chamber. Oxidative damage to HDL was assessed by measuring conjugated diene formation and changes in electrophoretic migration. Y-HDL had more anti-inflammatory activity than E-HDL. The conjugated diene content and the electrophoretic mobility of E-HDL were higher than those of Y-HDL. Y-PON1 had significant anti-inflammatory activity, reducing ICAM-1 expression by 32·64 (SD 2·63)%, while E-PON1 had no significant effect. THP-1 chemotaxis measurements confirmed the ICAM-1 expression results. The 12 weeks of EVOO consumption significantly increased the anti-inflammatory activities of both HDL and PON1. The anti-inflammatory activity of HDL was modulated by PON1 and was lower in the elderly volunteers. EVOO consumption increased the anti-inflammatory effect of HDL and reduced the age-related decrease in anti-atherogenic activity.

  18. In Silico Analyses of Substrate Interactions with Human Serum Paraoxonase 1

    Science.gov (United States)

    2008-01-01

    enzyme that exhibits a broad spectrum of hydrolytic activ- ities, including the hydrolysis of various organo - phosphates, esters, and recently...HuPON1 is highly simi- lar in amino acid sequence to the recombinant rePON1, allowing a reliable 3D structural model of HuPON1 to be constructed. The...with Tripos force field) was performed to remove unphysical internal strains in the molecules. Homology modeling The 3D structural model of HuPON1 was

  19. Low serum PON1 activity: an independent risk factor for coronary artery disease in North-West Indian type 2 diabetics.

    Science.gov (United States)

    Gupta, Nidhi; Binu, K B K; Singh, Surjit; Maturu, Nagarjuna V; Sharma, Yash P; Bhansali, Anil; Gill, Kiran Dip

    2012-04-25

    The paraoxonase (PON1) gene polymorphisms are known to affect the PON1 activity and coronary artery disease (CAD) risk. Studies done so far have given conflicting results. In the present study, we determined the role of PON1 genetic variants and PON1 activity in the development of CAD in North-West Indian Punjabis, a distinct ethnic group, having high incidence of both CAD and type 2 diabetes. 300 angiographically proven CAD with type 2 diabetics and 250 type 2 diabetics with no clinically evident CAD were enrolled. Serum PON1 activity and genotyping of coding (Q192R, L55M) and promoter (-909G/C, -162A/G, -108C/T) region polymorphisms were carried out and haplotypes were determined using PHASE software. The serum PON1 activity was significantly lower in CAD with type 2 diabetics as compared to diabetics alone (51.0 vs. 114.2nmol/min/ml). In logistic regression model after adjusting for confounding variables, lower PON1 activity was found to be significantly associated with CAD risk in type 2 diabetics with OR being 16.8 (95% CI: 10.2-27.7). The lower serum PON1 activity, irrespective of genotypes and haplotypes is a risk factor for development of CAD in North-West Indian Punjabis with type 2 diabetics.

  20. Serum paraoxonase activity, total thiols levels, and oxidative status in patients with acute brucellosis.

    Science.gov (United States)

    Esen, Ramazan; Aslan, Mehmet; Kucukoglu, Mehmet Emin; Cıkman, Aytekin; Yakan, Umit; Sunnetcioglu, Mahmut; Selek, Sahbettin

    2015-06-01

    It is well known that paraoxonase-1 (PON1) activity may decrease during the course of infection and inflammation. The aim of this study was to investigate serum PON1 activity, oxidative status, and thiols levels in patients with acute brucellosis. In addition, we investigated the PON1 phenotype in patients with acute brucellosis. Thirty patients with acute brucellosis and 35 healthy controls were enrolled. Serum paraoxonase and arylesterase activities, thiols levels, lipid hydroperoxide levels, total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined. Serum basal and salt-stimulated paraoxonase-arylesterase activities, TAC levels and thiols levels were significantly lower in patients with acute brucellosis than controls (for all, p brucellosis. These results indicate that lower PON1 activity is associated with oxidant-antioxidant imbalance.

  1. Organophosphate pesticide exposure, PON1, and neurodevelopment in school-age children from the CHAMACOS study.

    Science.gov (United States)

    Eskenazi, Brenda; Kogut, Katherine; Huen, Karen; Harley, Kim G; Bouchard, Maryse; Bradman, Asa; Boyd-Barr, Dana; Johnson, Caroline; Holland, Nina

    2014-10-01

    Organophosphate (OP) pesticides remain widely used in agriculture. Previously, we reported that PON1 genotype was directly associated with neurodevelopment at age two, and that PON1 genotype may increase susceptibility to OP exposure. We examined the relationships of maternal and child PON1 genotype and enzyme activity levels and neurodevelopment at school age and examined their interaction with maternal dialkyl phosphate (DAP) metabolite levels to investigate differential susceptibility to OP-related neurotoxicity. Participants were from the CHAMACOS longitudinal birth cohort of Latino families in an agricultural region of California. We measured DAP metabolites of OP pesticides in maternal and child urine samples, and analyzed PON1192 and PON1-108 genotypes and enzyme activity [arylesterase (ARYase), paraoxonase (POase)] in maternal and child blood. We examined their association with children׳s performance on the Conners׳ Kiddie Continuous Performance Test (K-CPT) at 5 years (n=296) and the Wechsler Intelligence Scale for Children (WISC-IV) at 7 years (n=327). Maternal and child PON1 genotype was not related to performance on K-CPT or WISC, although WISC scores tended to be lowest in children and children of mothers who carried the PON-108TT genotype. Pregnancy ARYase levels were positively associated with all WISC subscales (e.g., 4.0 point increase in Full Scale IQ per standard deviation increase in ARYase, 95% CI=1.6, 6.4), while pregnancy POase levels were positively associated with WISC Processing Speed only. Maternal PON1-108 weakly modified the relationship of maternal DAPS and K-CPT scores (pinteraction=0.21) and WISC verbal IQ (pinteraction=0.71). The association between DAPs and Full-Scale IQ was strongest for children of mothers with lowest-tertile ARYase levels (pinteraction=0.27). This relationship held for both diethyl and dimethyl DAPs and for all subscales of the WISC. We extend our previous findings that PON1 genotype and enzyme levels may be

  2. Studies on the correlation of PON1 gene rs854572 single nucleotide polymorphism to clopidogrel resistance

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    Teng-fei LIU

    2012-10-01

    Full Text Available Objective To investigate the correlation of the single nucleotide polymorphism (SNP of PON1 (Paraoxonase-1 gene rs854572 to the occurrence of clopidogrel resistance (CR. Methods A case-control method was employed in present study. A total of 850 hospitalized patients with coronary artery diseases (CAD in General Hospital of Shenyang Command were enrolled. The residual platelet aggregation rate (RPA induced by 20μmol/L of adenosine diphosphate (ADP was detected by optical nephelometry, and RPA≥70% was defined as CR. Accordingly, all the enrolled 850 patients were then divided into CR group (n=215 and non-CR (NCR group (n=635. Polymerase chain reaction (PCR and pyrophosphate sequencing were executed to determine the genotypes and the allele frequencies of PON1 gene rs854572. Results The genotype frequencies in rs854572 of PON1 gene conformed well to the Hardy-Weinberg equilibrium in both CR group and NCR group. Three frequencies of genotype CC, CG and GG were 23.7%, 49.3%, 27.0% in CR group, and 24.1%, 50.2%, 25.7% in NCR groups, respectively. No significant difference in genotype and allele frequency existed between CR group and NCR group (P=0.93 and 0.76, respectively. Logistic regression analysis revealed that no correlation between rs854572 SNP of PON1 gene and the formation of CR in patients with CAD after adjustment of correspondent factors including age, gender, body mess index, smoking, hypertension, diabetes mellitus and hyperlipidemia. Conclusions It is considered that no correlation exists between PON1 gene rs854572 polymorphism and clopidogrel resistance in patients with coronary heart disease.

  3. Coincubation of PON1, APO A1, and LCAT increases the time HDL is able to prevent LDL oxidation.

    Science.gov (United States)

    Hine, David; Mackness, Bharti; Mackness, Mike

    2012-02-01

    The inhibition of low-density lipoprotein (LDL) oxidation by high-density lipoprotein (HDL) is a major antiatherogenic property of this lipoprotein. This activity is due, in part, to HDL associated proteins. However, whether these proteins interact in the antioxidant activity of HDL is unknown. LDL was incubated with apolipoprotein A1 (apo A1), lecithin:cholesterol acyltransferase (LCAT), and paraoxonase-1 (PON1) alone or in combination, in the presence or absence of HDL under oxidizing conditions. LDL lipid peroxide concentrations were determined. Apo A1, LCAT, and PON1 all inhibit LDL oxidation in the absence of HDL and enhance the ability of HDL to inhibit LDL oxidation. Their effect was additive rather than synergistic; the combination of these proteins significantly enhanced the length of time LDL was protected from oxidation. This seemed to be due to the ability of PON1 to prevent the oxidative inactivation of LCAT. Apo A1, LCAT, and PON1 can all contribute to the antioxidant activity of HDL in vitro. The combination of apo A1, LCAT, and PON1 prolongs the time that HDL can prevent LDL oxidation, due, at least in part, to the prevention LCAT inactivation.

  4. Maternal exposure to floricultural work during pregnancy, PON1 Q192R polymorphisms and the risk of low birth weight

    Energy Technology Data Exchange (ETDEWEB)

    Moreno-Banda, G.; Blanco-Munoz, J. [Population Health Research Center, National Institute of Public Health, Avenida Universidad 655, Colonia Santa Maria Ahuacatitlan, 62508 Cuernavaca, Morelos (Mexico); Lacasana, M., E-mail: marina.lacasana.easp@juntadeandalucia.es [Andalusian School of Public Health, Campus Universitario de la Cartuja, Cuesta del Observatorio, 4, 18080 Granada (Spain); CIBER of Epidemiology and Public Health (CIBERESP) (Spain); Rothenberg, S.J. [Population Health Research Center, National Institute of Public Health, Avenida Universidad 655, Colonia Santa Maria Ahuacatitlan, 62508 Cuernavaca, Morelos (Mexico); Center of Research and Advanced Studies, National Institute Polytechnic, Department of Toxicology, Av, Instituto Politecnico Nacional No. 2508, Col. San Pedro Zacatenco, Deleg. Gustavo A. Madero, 07360 Mexico, D.F. (Mexico); Aguilar-Garduno, C. [Andalusian School of Public Health, Campus Universitario de la Cartuja, Cuesta del Observatorio, 4, 18080 Granada (Spain); Andalusian Observatory of Environmental Health, Campus Universitario de la Cartuja, Cuesta del Observatorio, 4, 18080 Granada (Spain); Gamboa, R. [Department of Physiology, National Institute of Cardiology ' Ignacio Chavez' , Juan Badiano 4, Section XVI, 14080, Mexico DF (Mexico); Perez-Mendez, O. [Department of Molecular Biology and cardiovascular Diseases Genomic and Proteomic, National Institute of Cardiology ' Ignacio Chavez' , Juan Badiano 4, Section XVI, 14080, Mexico DF (Mexico)

    2009-10-15

    Background: Although there is evidence from animal studies of impaired reproductive function by exposure to organophosphates (OP), the effects on birth weight have not been sufficiently evaluated in epidemiological studies. Paraoxonase (PON1) detoxifies organophosphates by cleavage of active oxons. Some PON1 gene polymorphisms could reduce the enzyme activity and increase susceptibility to OP toxicity. Objective: To assess the association between maternal exposure to floriculture during pregnancy and the risk of low birth weight (< 2500 g) in their offspring, as well as to evaluate the interaction between this exposure and maternal genotype for PON1 Q192R polymorphisms. Materials and methods: A cross sectional study was carried out in two Mexican states (States of Mexico and Morelos) with high frequencies of greenhouse activity. We interviewed and collected blood samples from 264 females (floriculturists or partners of floricultural workers) who became pregnant during the 10 years prior to the interview. The questionnaire measured socioeconomic characteristics, tobacco and alcohol consumption, diseases and occupational and reproductive history. We also applied a food frequency questionnaire. Information was obtained pertaining to 467 pregnancies. DNA was extracted from white cells, and PON1 genotype was determined by Restriction Fragment Length Polymorphism for Q192R polymorphisms. Results were analyzed with generalized estimating equations models. Results: After adjusting for potential confounders, we detected a statistically significant interaction between maternal exposure to flower growing work during pregnancy and PON1 Q192R polymorphisms on risk of low birth weight. The risk of having a baby with LBW is nearly six times higher if a mother is a floriculture worker during pregnancy and has PON1 192RR genotype (OR 5.93, 95% CI 1.28, 27.5). Conclusion: These results suggest that the interaction between maternal floriculture work during pregnancy and 192RR PON1

  5. Evaluation of Paraoxonase, Arylesterase and Malondialdehyde Levels in Schizophrenia Patients Taking Typical, Atypical and Combined Antipsychotic Treatment

    Science.gov (United States)

    Güneş, Mehmet; Camkurt, Mehmet Akif; Bulut, Mahmut; Demir, Süleyman; İbiloğlu, Aslıhan Okan; Kaya, Mehmet Cemal; Atlı, Abdullah; Kaplan, İbrahim; Sir, Aytekin

    2016-01-01

    Objective Human serum paraoxonase (PON1) prevents lipids from peroxidation and functions as an antioxidant mechanism. Malonyldialdehyde (MDA) is the final product of lipid peroxidation and can be used as an indicator of oxidative stress. The aim of this study was to investigate PON1, MDA, and arylesterase (ARY) levels in schizophrenic patients who are taking typical, atypical, or combined (typical and atypical) antipsychotic drug treatment, with respect to those of healthy controls. Methods We evaluated 41 patients (11 taking typical antipsychotics, 19 taking atypical antipsychotics, 11 taking combined anti-psychotics) and 43 healthy controls. Results MDA levels were higher in schizophrenic patients taking typical antipsychotics compared with healthy controls (p=0.001). ARY levels were higher in patients taking atypical antipsychotics compared with healthy controls (p=0.005). PON1 activity was similar in all groups. Conclusion Our results indicate that treatment with typical antipsychotic drugs could be related to increased MDA levels; and antipsychotic medication may increase PON1 levels in schizophrenic patients. PMID:27776386

  6. Associations of PON1 and genetic ancestry with obesity in early childhood.

    Directory of Open Access Journals (Sweden)

    Karen Huen

    Full Text Available Obesity in children has become an epidemic in the U.S. and is particularly prominent in minority populations such as Mexican-Americans. In addition to physical activity and diet, genetics also plays a role in obesity etiology. A few studies in adults and adolescents suggest a link between obesity and paraoxonase 1 (PON1, a multifunctional enzyme that can metabolize organophosphate pesticides and also has antioxidant properties. We determined PON1192 genotype and arylesterase levels (ARYase, measure of PON1 enzyme quantity, to characterize the relationship between PON1 and obesity in young Mexican-American children (n = 373 living in an agricultural community in California. Since PON1 polymorphisms and obesity both vary between ethnic groups, we estimated proportional genetic ancestry using 106 ancestral informative markers (AIMs. Among children, PON1192 allele frequencies were 0.5 for both alleles, and the prevalence of obesity was high (15% and 33% at ages two and five, respectively. The average proportion of European, African, and Native American ancestry was 0.40, 0.09, and 0.51, yet there was wide inter-individual variation. We found a significantly higher odds of obesity (9.3 and 2.5- fold in PON1192QQ children compared to PON1192RR children at ages two and five, respectively. Similar relationships were seen with BMI Z-scores at age two and waist circumference at age five. After adjusting for genetic ancestry in models of PON1 and BMI Z-score, effect estimates for PON1192 genotype changed 15% and 9% among two and five year old children, respectively, providing evidence of genetic confounding by population stratification. However even after adjustment for genetic ancestry, the trend of increased BMI Z-scores with increased number of PON1192 Q alleles remained. Our findings suggest that PON1 may play a role in obesity independent of genetic ancestry and that studies of PON1 and health outcomes, especially in admixed populations, should

  7. Paraoxonase 1 Activity in Endocrine Diseases

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    Özlem Tarçın

    2011-06-01

    Full Text Available Paraoxonase is an esterase bound to high-density lipoproteins which by metabolizing lipid peroxides, prevents their accumulation on low-density lipoproteins. It also hydrolyzes various organophosphorus compounds. Considering the role of PON1 in hydrolyzing phospholipid and cholesteryl-ester hydroperoxides and thus protecting lipoproteins against oxidative modification, it can be concluded that PON1 may be an indicator of the risk of atherosclerosis/coronary artery disease development. Recent studies have also shown that PON activity was related to several disorders, including endocrine disorders as well. In this paper, we review the relation of PON1 activity with endocrine diseases like diabetes, thyroid dysfunction, osteoporosis, polycystic ovary syndrome (PCOS, obesity and dyslipidemia. Turk Jem 2011; 15: 33-8

  8. Haplotype-phenotype relationships of paraoxonase-1.

    Science.gov (United States)

    Chen, Jia; Chan, Wendy; Wallenstein, Sylvan; Berkowitz, Gertrud; Wetmur, James G

    2005-03-01

    Paraoxonase 1 (PON1) is an enzyme with multiple activities, including detoxification of organophosphates. It is believed to be important in preventing neurotoxic damage and has also been implicated in atherosclerosis. The PON1 gene contains five common polymorphisms, three in the promoter (-909G > C, -162A > G, -108C > T) and two in the coding region (M55L, Q192R) with varying but incomplete linkage disequilibrium. Our previous study showed that functional polymorphisms in PON1 were strongly associated with enzymatic activity in both pregnant women [26-30 weeks of gestation] and neonates. However, there was substantial overlapping of enzyme activities between genotypes. In this study, we investigated whether haplotype (genotype + phase) information would strengthen the genotype-phenotype relationship for PON1. The study consisted of a multiethnic population of 402 mothers and 229 neonates. Haplotypes were imputed by two widely used programs, PHASE and tagSNPs, which yielded very similar results. There were seven haplotypes with a frequency of 5% or higher in at least one ethnic group of the study population. Haplotype composition varied substantially with respect to ethnicity. Haplotypes in Caucasians and African-Americans showed the largest difference, and Caribbean Hispanics seemed to be a mixture of Caucasian and African ancestry. Collectively, the genetic (genotype or haplotype) contribution to PON1 enzymatic activity (measured as phenylacetate hydrolysis) was greater in neonates compared with mothers. Specifically, 16.6% of PON1 variability was explained by genotypes in mothers compared with 30.9% in neonates. Haplotype information offered a slightly increased power in predicting PON1 activity; they explained 35.5% and 19.3% of PON1 variability in neonates and mothers, respectively.

  9. Polymorphisms in three obesity-related genes (LEP, LEPR, and PON1) and breast cancer risk: a meta-analysis.

    Science.gov (United States)

    Liu, Chibo; Liu, Liu

    2011-12-01

    Common genetic variations in the leptin (LEP), leptin receptor (LEPR), and paraoxonase 1 (PON1) genes have been considered to be implicated in the development of breast cancer. However, the results were inconsistent. In this study, a meta-analysis was performed to assess the associations of five polymorphisms, including LEP G2548A, LEPR Q223R, LEPR Lys109Arg, PON1 L55M, and PON1 Q192R polymorphisms, with breast cancer risk. Published literature from PubMed, ISI Web of Science, Embase databases, CNKI, and Wanfang Data were retrieved. All studies evaluating the association between LEP G2548A, LEPR Q223R, LEPR Lys109Arg, PON1 L55M, or PON1 Q192R polymorphism and breast cancer risk were included. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Three studies (2,003 cases and 1,967 controls) for LEP G2548A polymorphism, nine studies (4,627 cases and 5,476 controls) for LEPR Q223R polymorphism, five studies (2,759 cases and 2,573 controls) for LEPR Lys109Arg polymorphism, four studies (1,517 cases and 1,379 controls) for PON1 L55M polymorphism, and five studies (1,575 cases and 2,283 controls) for PON1 Q192R polymorphism were included in the meta-analysis. Overall, the results showed null significant association between LEP G2548A, LEPR Q223R, LEPR Lys109Arg, or PON1 Q192R polymorphism and breast cancer risk; however, PON1 L55M was significantly associated with breast cancer risk overall (MM vs. LL: OR = 2.16; 95% CI, 1.76-2.66). For LEPR Q223R polymorphism, further subgroup analysis suggested that the association was only statistically significant in East Asians (OR = 0.50; 95% CI, 0.36-0.70) but not in Caucasians (OR = 1.06; 95% CI, 0.77-1.45) or Africans (OR = 1.30; 95% CI, 0.83-2.03). The present meta-analysis suggested that LEPR Q223R polymorphism might be implicated in the development of breast cancer in East Asians; PON1 L55M might increase breast cancer risk. However, given the limited

  10. Exploring the Role of Paraoxonases in the Pathogenesis of Coronary Artery Disease: A Systematic Review

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    David Abelló

    2014-11-01

    Full Text Available Paraoxonases (PON are three enzymes (PON1, PON2 and PON3 that play a role in the organism’s antioxidant system; alterations in which are associated with diseases involving oxidative stress. In this review, we summarize the evidence of PON related to the pathogenesis of coronary artery disease (CAD and atherosclerosis. We searched three electronic databases (PubMed, Scopus and Cochrane Database with no date limit. All of the articles selected investigated PON enzymatic activity and/or PON gene polymorphisms. The selection focused on PON in relation to atherosclerosis, CAD and myocardial infarction. The exclusion criteria were a sample size <100 patients, non-human studies, editorials and systematic reviews without restrictions on the country of origin. With these criteria, we identified thirty-five prospective studies published between 1986 and 2014 with a total of 28,164 participants. The relationship between PON gene polymorphisms and CAD was not conclusive, but most studies support the concept that alterations in PON1 enzymatic activity levels do influence atheroma formation. Conversely, relationships between PON2 and PON3 vs. CAD have not been extensively investigated. Our review of the current data concludes that the bases of paraoxonases involvement in atherosclerosis are poorly understood and that this issue requires future comprehensive, multi-centered studies.

  11. Aerobic Training Modulates the Effects of Exercise-Induced Oxidative Stress on PON1 Activity: A Preliminary Study

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    Aneta Otocka-Kmiecik

    2014-01-01

    Full Text Available The aim of the study was to compare the effect of maximal exercise (ME on paraoxonase (PON and arylesterase (ARE activity depending on lifestyle in respect to physical activity. The study was performed on 46 young men divided into two groups: sedentary (S and physically active (PA. All participants performed ME on a treadmill. PON1 activities, FRAP, uric acid, bilirubin, TBARS, and lipid profile were determined in their blood before, at the bout of, and after ME. No significant differences in PON1 activities were found between S and PA subjects at baseline. Nearly all biochemicals increased at ME in both groups. Both PON and ARE activity increased at the bout of ME in PA subjects and only ARE activity in S subjects. ARE/HDL-C ratio increased at the bout of ME in PA and S subjects. The difference in PON1 activity response to ME between study groups may be a result of adaptation of PA subjects to regular physical activity. We suggest that PON1 activity may be a marker of antioxidant protection at ME and an indicator of adaptation to exercise.

  12. Purification and Characterization of Functional Human Paraoxonase-1 Expressed in Trichoplusia ni Larvae

    Science.gov (United States)

    2010-01-01

    to that of 293T-produced HuPON1, rHuPON1 had a 2.5-foldfor GF), no evidence of saturation was detected, indicating that KM [S]. The Michaelis – Menten ...were determined by ichaelis– Menten steady state kinetics. The data were fit to the odel using Prism 4.03 software (GraphPad, La Jolla, CA). R2 values

  13. Paraoxonase 1 genotype-phenotype correlation in patients with metabolic syndrome.

    Science.gov (United States)

    Ciumărnean, Lorena; Dronca, Eleonora; Vesa, Ştefan Cristian; Sâmpelean, Dorel; Buzoianu, Anca Dana; Achimaş-Cadariu, Andrei

    2015-01-01

    The aim of the study was to investigate the influence of three single nucleotide polymorphisms (SNPs) (-108C>T, -162A>G and -909G>C) from the promoter region of paraoxonase 1 (PON1) gene on the enzyme activity, in patients with metabolic syndrome (MS). The study group consisted of 61 individuals with MS and the control group of 73 individuals without MS, matched for age and gender. For each individual, clinical and genetic parameters with possible influence on PON1 activities (paraoxonase, arylesterase and lactonase) were measured. PON1 genotyping was performed with PCR-RFLP, using specific primers and restriction enzymes. We found no differences for distribution of PON1 -108C>T, -162A>G and -909G>C polymorphisms, between the two groups (p-NS). The -108C>T and -909G>C polymorphisms were associated with paraoxonase (p=0.03, p=0.006, respectively), arylesterase (p162A>G polymorphism was not associated with paraoxonase (p-NS) or lactonase (p-NS) activities, but influenced the arylesterase activity (p=0.03). PON1 activities were influenced by all three polymorphisms, regardless of the presence of MS.

  14. Inhibitory effect of the paraoxonase gene on the formation of rabbit coronary atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Jing Bai; Hui Zhou; Xin-Hong Yang; Hua-Fen Liu; Yan-Yan Meng

    2013-01-01

    Objective: To observe the effect on the inhibition of coronary atherosclerosis hardening of the paraoxonase gene (PON-1) which transfected to the rabbit epicardial adipose tissue. Methods:Rabbit coronary atherosclerosis model was established by high-fat feeding, liposome-encapsulated recombinant plasmid pEGFP-PON-1 50 μL was injected to the rabbit pericardial cavity, and was harvested 4 weeks after transfection. Results: The epicardial fat transfected PON-1 gene had effect on the high lipid level. It significantly increased expression of PON-1 in peripheral arterial vascular tissue (P<0.05); and significantly reduced total cholesterol and low-density lipoprotein cholesterol levels (P<0.05), and the thickness ratio of coronary artery intima/media (P <0.05). Conclusions: The injection of the PON-1 gene in the pericardial cavity can effectively suppress the formation of coronary atherosclerosis.

  15. Investigation of PON1 activity and MDA levels in patients with epilepsy not receiving antiepileptic treatment

    Directory of Open Access Journals (Sweden)

    Dönmezdil N

    2016-04-01

    Full Text Available Nilüfer Dönmezdil, Mehmet Uğur Çevik, Hasan Hüseyin Özdemir, Muhterem Taşin Department of Neurology, Dicle University, Diyarbakır, Turkey Purpose: There are many studies dedicated to researching the etiopathogenesis of epilepsy. In such research, oxidative and antioxidant indicators of etiopathogenesis have also been examined under the scope. Drawing on a group of patients with epilepsy who were receiving no treatment, we have tried to evaluate whether or not an increase in oxidative indicators is linked directly with the disorder, independent of epileptic medicaments.Methods: Thirty people in good health and 30 newly diagnosed with epilepsy and who received ambulatory treatment in the polyclinic of the Neurology Department took part in the study. The tests relating to serum malondialdehyde (MDA levels and paraoxonase 1 (PON1 activity were carried out in the biochemistry laboratory.Results: Even though the levels of MDA in the patient group (14.34±3.59 nmol/mL were found to be high compared to those of the control group, which consisted of people in good health (13.53±3.56 nmol/mL, there was no statistically significant difference. PON1 activity in the serum taken from people in the patient group (0.65±0.17 was lower in comparison to that observed in the serum of the control group (0.71±0.17 U/L. Nonetheless, it was not so low as to have significance from a statistical point of view.Conclusion: We conclude that such a high level of oxidative parameters should have been related to the disease and that statistically significant findings that emerged in some other studies could have been related to an antiepileptic treatment. Keywords: epilepsy, paraoxonase 1, malondialdehyde, oxidative stress, epilepsy, biochemical marker

  16. Indications that paraoxonase-1 contributes to plasma high density lipoprotein levels in familial hypercholesterolemia.

    Science.gov (United States)

    van Himbergen, Thomas M; Roest, Mark; de Graaf, Jacqueline; Jansen, Eugène H J M; Hattori, Hiroaki; Kastelein, John J P; Voorbij, Hieronymus A M; Stalenhoef, Anton F H; van Tits, Lambertus J H

    2005-03-01

    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 < 0.001; paraoxonase activity: r = 0.23, P = 0.01; diazoxonase activity: r = 0.29, P < 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.

  17. p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample

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    Daniel Zanetti Scherrer

    2015-07-01

    Full Text Available Background:Evidences suggest that paraoxonase 1 (PON1 confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL.Objective:To investigate the relationships between p.Q192R SNP of PON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample.Methods:We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age. Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA. Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317.Results:The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38; RQ = 46.96 (22.35; QQ = 85.35 (24.83 μmol/min; p Conclusion:In low-risk individuals, the presence of the p.192Q variant of PON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis.

  18. Novel Associations of Nonstructural Loci with Paraoxonase Activity

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    Ellen E. Quillen

    2012-01-01

    Full Text Available The high-density-lipoprotein-(HDL- associated esterase paraoxonase 1 (PON1 is a likely contributor to the antioxidant and antiatherosclerotic capabilities of HDL. Two nonsynonymous mutations in the structural gene, PON1, have been associated with variation in activity levels, but substantial interindividual differences remain unexplained and are greatest for substrates other than the eponymous paraoxon. PON1 activity levels were measured for three substrates—organophosphate paraoxon, arylester phenyl acetate, and lactone dihydrocoumarin—in 767 Mexican American individuals from San Antonio, Texas. Genetic influences on activity levels for each substrate were evaluated by association with approximately one million single nucleotide polymorphism (SNPs while conditioning on PON1 genotypes. Significant associations were detected at five loci including regions on chromosomes 4 and 17 known to be associated with atherosclerosis and lipoprotein regulation and loci on chromosome 3 that regulate ubiquitous transcription factors. These loci explain 7.8% of variation in PON1 activity with lactone as a substrate, 5.6% with the arylester, and 3.0% with paraoxon. In light of the potential importance of PON1 in preventing cardiovascular disease/events, these novel loci merit further investigation.

  19. Metformin administration induces hepatotoxic effects in paraoxonase-1-deficient mice.

    Science.gov (United States)

    García-Heredia, Anabel; Riera-Borrull, Marta; Fort-Gallifa, Isabel; Luciano-Mateo, Fedra; Cabré, Noemí; Hernández-Aguilera, Anna; Joven, Jorge; Camps, Jordi

    2016-04-05

    Metformin is the first-line pharmacological treatment of diabetes. In these patients, metformin reduces body weight and decreases the risk of diabetes-related complications such as cardiovascular disease. However, whether metformin elicits beneficial effects on liver histology is a controversial issue and, as yet, there is no consensus. Paraoxonase-1 (PON1), an enzyme synthesized mainly by the liver, degrades lipid peroxides and reduces oxidative stress. PON1 activities are decreased in chronic liver diseases. We evaluated the effects of metformin in the liver of PON1-deficient mice which, untreated, present a mild degree of liver steatosis. Metformin administration aggravated inflammation in animals given a standard mouse chow and in those fed a high-fat diet. Also, it was associated with a higher degree of steatosis in animals fed a standard chow diet. This report is a cautionary note regarding the prescription of metformin for the treatment of diabetes in patients with concomitant liver impairment.

  20. Serum paraoxonase 1 activity status in patients with liver disorders

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    Kedage Vivekananda

    2010-01-01

    Full Text Available Background/Aim: Paraoxonase 1 (PON1 is an esterase, exclusively synthesized by liver. The present study has two objectives: to determine the PON1 activity status in various disorders associated with hepatocellular damage and to correlate the changes of PON1 activity with the standard liver function and fasting lipid profile tests in these disorders. Patients and Methods: The study groups consisted of 95 patients with liver diseases including acute viral hepatitis (14, cirrhosis with portal hypertension (33, leptospirosis (14, sepsis and multi organ failure (15, left ventricular failure (9, and falciparum malaria (10; and 53 healthy controls. Serum PON1 activity was measured manually using spectrophotometer. Liver function test parameters and fasting lipid profile were performed in clinical chemistry auto analyzer (Hitachi 912. Results: The serum PON1 activity in patients with acute viral hepatitis and sepsis decreased significantly ( P < 0.001 and moderately in falciparum malaria ( P < 0.05. However, in patients with cirrhosis, leptospirosis and left ventricular patients, its activity did not change significantly. On applying Pearson correlation, serum PON1 activity correlated positively with high-density lipoprotein-cholesterol (HDL-C in patients with sepsis (r=0.633, P < 0.05, left ventricular failure patients (r=0.814, P < 0.05 and negatively with acute viral hepatitis patients (r=- 0.528, P < 0.05. Conclusion: PON1 activity has decreased significantly in acute viral hepatitis, sepsis with multi organ failure and falciparum malaria patients. Determination of PON1 activity may serve as a useful additional test in assessing these conditions.

  1. Paraoxonase genotype, LDL-oxidation and carotid atherosclerosis in male life-long smokers

    NARCIS (Netherlands)

    Himbergen, van T.; Roest, M.; Waart, de F.; Voorbij, H.; Tits, van L.; Stalenhoef, A.

    2004-01-01

    Paraoxonase (PON-1) is a high-density lipoprotein (HDL) associated enzyme that hydrolyzes lipid peroxides in vitro , which may therefore protect against the onset of atherosclerosis. Heavy smokers are more exposed to oxidative stress and hence at high-risk for oxidative modification of LDL. Our hypo

  2. Contrasting genetic influence of PON 1 coding gene polymorphisms ...

    African Journals Online (AJOL)

    Nadia Youssef Sadek Morcos

    2015-03-31

    Mar 31, 2015 ... c Toxicity Department, Poison Control Center, Ain Shams Universty Hospital, Egypt ... frequency distribution of PON1 Q192R polymorphism showed a highly ... at position 192, where either glutamine (Q) or arginine (R).

  3. Paraoxonase responses to exercise and niacin therapy in men with metabolic syndrome.

    Science.gov (United States)

    Taylor, James Kyle; Plaisance, Eric P; Mahurin, A Jack; Mestek, Michael L; Moncada-Jimenez, Jose; Grandjean, Peter W

    2015-01-01

    Our purpose was to characterize changes in paraoxonase 1 (PON1) activity and concentration after single aerobic exercise sessions conducted before and after 6 weeks of niacin therapy in men with metabolic syndrome (MetS). Twelve men with MetS expended 500 kcal by walking at 65% of VO2max before and after a 6-week regimen of niacin. Niacin doses were titrated by 500 mg/week from 500 to 1500 mg/day and maintained at 1500 mg/day for the last 4 weeks. Fasting blood samples were collected before and 24 hours after each exercise session and analyzed for PON1 activity, PON1 concentration, myeloperoxidase (MPO), apolipoprotein A1, oxidized low-density lipoprotein (oLDL), lipoprotein particle sizes and concentrations. PON1 activity, PON1 concentration, MPO, and oLDL were unaltered following the independent effects of exercise and niacin (P > 0.05 for all). High-density lipoprotein particle size decreased by 3% (P = 0.040) and concentrations of small very low-density lipoprotein increased (P = 0.016) following exercise. PON1 activity increased 6.1% (P = 0.037) and PON1 concentrations increased 11.3% (P = 0.015) with the combination of exercise and niacin. Exercise and niacin works synergistically to increase PON1 activity and concentration with little or no changes in lipoproteins or markers of lipid oxidation.

  4. Measurement of serum paraoxonase-1 activity in the evaluation of liver function

    Institute of Scientific and Technical Information of China (English)

    Jordi Camps; Judit Marsillach; Jorge Joven

    2009-01-01

    Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and found in the circulation associated with high-density lipoproteins. The physiological function of PON1 seems to be to degrade specific oxidized cholesteryl esters and oxidized phospholipids in lipoproteins and cell membranes. PON1 is, therefore, an antioxidant enzyme. Alterations in circulating PON1 levels have been reported in a variety of diseases involving oxidative stress including chronic liver diseases. Measurement of serum PON1 activity has been proposed as a potential test for the evaluation of liver function. However, this measurement is still restricted to research and has not been extensively applied in routine clinical chemistry laboratories. The reason for this restriction is due to the problem that the substrate commonly used for PON1 measurement,paraoxon, is toxic and unstable. The recent development of new assays with non-toxic substrates makes this proposal closer to a practical development. The present editorial summarizes PON1 biochemistry and function,its involvement with chronic liver impairment, and some aspects related to the measurement of PON1 activity in circulation.

  5. Serum Paraoxonase 1 Activity Is Associated with Fatty Acid Composition of High Density Lipoprotein

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    Maryam Boshtam

    2013-01-01

    Full Text Available Introduction. Cardioprotective effect of high density lipoprotein (HDL is, in part, dependent on its related enzyme, paraoxonase 1 (PON1. Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA. PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω6 fatty acids of HDL. Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health.

  6. Temperature dependence of binding and catalysis for human serum arylesterase/paraoxonase.

    Science.gov (United States)

    Debord, Jean; Bollinger, Jean-Claude; Harel, Michel; Dantoine, Thierry

    2014-02-01

    The influence of temperature upon the hydrolysis of phenyl acetate, catalysed by purified human serum arylesterase/paraoxonase (E. C. 3.1.8.1), was studied in the temperature range 10 °C-40 °C by spectrophotometry in TRIS buffer, pH 8.0, using both initial rate analysis and progress curve analysis. The kinetic parameters (catalytic constant k(cat); Michaelis constant K(m); product inhibition constant K(p)) were determined by nonlinear regression. All parameters increased with temperature, but the ratios k(cat)/K(m) and K(p)/K(m) remained practically constant. Binding of both substrate and reaction product (phenol) was exothermic. A negative entropic term accounted for about 50% of the enthalpy change for both the binding and catalytic steps. Thermodynamic analysis suggested that: (1) the rate-limiting step is the nucleophilic attack of the carbonyl group of the substrate by a water molecule, (2) the active site is preorganized with no induced fit, (3) the enzyme-bound calcium plays an important role in stabilizing both the substrate and the transition state. The practical implications of these results are discussed.

  7. Molecular Dynamics Approach in the Comparison of Wild-Type and Mutant Paraoxonase-1 Apoenzyme Form

    Science.gov (United States)

    Amine, Khadija; Miri, Lamia; Naimi, Adil; Saile, Rachid; El Kharrim, Abderrahmane; Mikou, Afaf; Kettani, Anass

    2015-01-01

    There is some evidence linking the mammalian paraoxonase-1 (PON1) loops (L1 and L2) to an increased flexibility and reactivity of its active site with potential substrates. The aim of this work is to study the structural, dynamical, and functional effects of the most flexible regions close to the active site and to determine the impact of mutations on the protein. For both models, wild-type (PON1wild) and PON1 mutant (PON1mut) models, the L1 loop and Q/R and L/M mutations were constructed using MODELLER software. Molecular dynamics simulations of 20 ns at 300 K on fully modeled PON1wild and PON1mut apoenzyme have been done. Detailed analyses of the root-mean-square deviation and fluctuations, H-bonding pattern, and torsion angles have been performed. The PON1wild results were then compared with those obtained for the PON1mut. Our results show that the active site in the wild-type structure is characterized by two distinct movements of opened and closed conformations of the L1 and L2 loops. The alternating and repetitive movement of loops at specific times is consistent with the presence of 11 defined hydrogen bonds. In the PON1mut, these open-closed movements are therefore totally influenced and repressed by the Q/R and L/M mutations. In fact, these mutations seem to impact the PON1mut active site by directly reducing the catalytic core flexibility, while maintaining a significant mobility of the switch regions delineated by the loops surrounding the active site. The impact of the studied mutations on structure and dynamics proprieties of the protein may subsequently contribute to the loss of both flexibility and activity of the PON1 enzyme. PMID:26417201

  8. Significant interethnic differencies in functional variants of PON1 and P2RY12 genes in Roma and Hungarian population samples.

    Science.gov (United States)

    Janicsek, Ingrid; Sipeky, Csilla; Bene, Judit; Duga, Balazs; Melegh, Bela I; Melegh, Bela; Sümegi, Katalin; Jaromi, Luca; Magyari, Lili; Melegh, Bela

    2015-01-01

    Antiplatelet therapy with clopidogrel is one of the most common therapies given to patients worldwide. However, the clinical efficacy and toxicity of clopidogrel is not constant in every patient due to interindividual variations. There are several factors that contribute to these interindividual differencies such as SNPs in genes of specific receptors and enzymes. PON1 (paraoxonase 1) plays an important role in the bioactivation of clopidogrel. Single nucleotide polymorphisms of this gene decrease the activity of paraoxonase enzyme and lead to an unefficient clopidogrel effect. P2RY12 (purinergic receptor P2Y, G-protein coupled, 12) gene is coding a receptor, which is situated on the surface of the platelets and plays a role in ADP-induced platelet aggregation. In this study we investigated 2 functional SNPs of PON1 gene (rs662 and rs854560) and 3 variants of the P2RY12 gene (rs2046934, rs6798347, rs6801273) in samples pooled from average Hungarian Roma and Hungarian population samples with PCR-RFLP method. For the PON1 variants we detected that the R allele frequency was significantly lower in the Roma group compared to the Hungarian population. (0.249 vs 0.318 p Roma than in Hungarians (0.332 vs 0.290 p Romas (1.4 vs 0.2 %, p Roma people that has not been reported for other populations.

  9. Identification of paraoxonase 3 in rat liver microsomes: purification and biochemical properties.

    Science.gov (United States)

    Rodrigo, Lourdes; Gil, Fernando; Hernandez, Antonio F; Lopez, Olga; Pla, Antonio

    2003-01-01

    Three paraoxonase genes (PON1, PON2 and PON3) have been described so far in mammals. Although considerable information is available regarding PON1, little is known about PON2 and PON3. PON3 has been isolated recently from rabbit serum [Draganov, Stetson, Watson, Billecke and La Du (2000) J. Biol. Chem. 275, 33435-33442] and liver [Ozols (1999) Biochem. J. 338, 265-275]. In the present study, we have identified the presence of PON3 in rat liver microsomes and a method for the purification to homogeneity is presented. PON3 has been purified 177-fold to apparent homogeneity with a final specific activity of 461 units/mg using a method consisting of seven steps: solubilization of the microsomal fraction, hydroxyapatite adsorption, chromatography on DEAE-Sepharose CL-6B, non-specific affinity chromatography on Cibacron Blue 3GA, two DEAE-cellulose steps and a final affinity chromatography on concanavalin A-Sepharose. SDS/PAGE of the final preparation indicated a single protein-staining band with an apparent molecular mass of 43 kDa. The isolated protein was identified by nanoelectrospray MS. Internal amino acid sequences of several peptides were determined and compared with those of human, rabbit and mouse PON3, showing a high similarity. Some biochemical properties of PON3 were also studied, including optimum pH, K(m) and heat and pH stability. PMID:12946270

  10. Interaction between prenatal pesticide exposure and a common polymorphism in the PON1 gene on DNA methylation in genes associated with cardio-metabolic disease risk

    DEFF Research Database (Denmark)

    Declerck, Ken; Remy, Sylvie; Wohlfahrt-Veje, Christine

    2017-01-01

    Background: Prenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (PON1) Q192R genotype and prenatal pesticide exposure leading to an adverse cardio-metabolic risk profile at school age. However......, the molecular mechanisms involved have not yet been resolved. It was hypothesized that epigenetics might be involved. The aim of the present study was therefore to investigate whether DNA methylation patterns in blood cells were related to prenatal pesticide exposure level, PON1 Q192R genotype, and associated...... metabolic effects observed in the children. Methods: Whole blood DNA methylation patterns in 48 children (6–11 years of age), whose mothers were occupationally unexposed or exposed to pesticides early in pregnancy, were determined by Illumina 450 K methylation arrays. Results: A specific methylation profile...

  11. The association between paraoxonase 1 gene polymorphisms and polycystic ovarian syndrome.

    Science.gov (United States)

    Gu, H F; Mou, M; Liang, Z G; Sun, C; Ren, X Y; Xiao, Y B

    2016-12-30

    Some studies investigated the association of paraoxonase 1 (PON1) polymorphisms with polycystic ovarian syndrome (PCOS) risk. However, the result was still inconsistent. The aim of this study was to investigate whether there is an association between the PON1 polymorphisms and PCOS risk. Electronic databases, such as PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) databases, were searched for identification of the studies. The associations between PON1 polymorphisms and PCOS risk was quantified using ORs with 95% CIs. A total of 8 eligible studies with 2272 cases and 1811 controls were included in this meta-analysis. PON1 Leu55Met polymorphism was associated with a significantly increased risk of PCOS (OR=1.31; 95%CI, 1.10-1.55). However, no association was found in Asians and Caucasians (Table 2). We also found that PON1 Q192R polymorphism was associated with a significantly increased risk of PCOS (OR=1.81; 95%CI, 1.17-2.82). Additionally, this polymorphism increased PCOS risk in Asians (OR=1.26; 95%CI, 1.13-1.41). Furthermore, PON1 C108T polymorphism showed increased PCOS risk (OR=1.46; 95%CI, 1.08-1.97). No association between this polymorphism and PCOS risk was found in Asians and Caucasians. In conclusion, this meta-analysis suggested that PON1 polymorphisms were associated with PCOS risk.

  12. Relationship between paraoxonase 1 activity and high density lipoprotein concentration during naturally occurring babesiosis in dogs.

    Science.gov (United States)

    Rossi, G; Kuleš, J; Rafaj, R Barić; Mrljak, V; Lauzi, S; Giordano, A; Paltrinieri, S

    2014-10-01

    Paraoxonase 1 (PON1) is a negative acute phase protein bound to high density lipoproteins (HDL) and during the acute phase response (APR) protects HDL from peroxidation. The aim of this study was to assess the relationship between PON1 and HDL in canine babesiosis, a disease characterized by oxidative damages and by an APR. PON1, HDL and C-reactive protein (CRP), were measured in blood collected from 15 controls and 29 dogs with babesiosis sampled at admission, and on days 1 and 7 after treatment. At admission, PON1 and HDL were significantly lower in affected dogs. HDL concentration increased at day 1 while PON1 increased and CRP decreased at day 7. This suggests that the decrease of PON1 at admission is in part due to an increased consumption, the decreased HDL may depend on lipid peroxidation and its rapid increase after treatment may depend on the antioxidant activity of PON1. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Association of organophosphate pesticide exposure and paraoxonase with birth outcome in Mexican-American women.

    Directory of Open Access Journals (Sweden)

    Kim G Harley

    Full Text Available BACKGROUND: Epidemiologic studies suggest that maternal organophosphorus (OP pesticide exposure is associated with poorer fetal growth, but findings are inconsistent. We explored whether paraoxonase (PON1, a key enzyme involved in detoxification of OPs, could be an effect modifier in this association. METHODS: The study population included 470 pregnant women enrolled in the CHAMACOS Study, a longitudinal cohort study of mothers and children living in an agricultural region of California. We analyzed urine samples collected from mothers twice during pregnancy for dialkyl phosphate (DAP metabolites of OP pesticides. We analyzed maternal and fetal (cord blood samples for PON1 genotype (PON1(192 and PON1(-108 and enzyme activity (paraoxonase and arylesterase. Infant birth weight, head circumference, and gestational age were obtained from medical records. RESULTS: Infants' PON1 genotype and activity were associated with birth outcome, but mothers' were not. Infants with the susceptible PON1(-108TT genotype had shorter gestational age (β = -0.5 weeks, 95% Confidence Interval (CI: -0.9, 0.0 and smaller head circumference (β = -0.4 cm, 95% CI: -0.7, 0.0 than those with the PON1(-108CC genotype. Infants' arylesterase and paraoxonase activity were positively associated with gestational age. There was some evidence of effect modification with DAPs: maternal DAP concentrations were associated with shorter gestational age only among infants of the susceptible PON1(-108TT genotype (p-value(interaction = 0.09. However, maternal DAP concentrations were associated with larger birth weight (p-value(interaction = 0.06 and head circumference (p-value(interaction<0.01 in infants with non-susceptible genotypes. CONCLUSIONS: Infants whose PON1 genotype and enzyme activity levels suggested that they might be more susceptible to the effects of OP pesticide exposure had decreased fetal growth and length of gestation. PON1 may be another factor

  14. Immunohistochemical Analysis of Paraoxonases and Chemokines in Arteries of Patients with Peripheral Artery Disease

    Directory of Open Access Journals (Sweden)

    Anna Hernández-Aguilera

    2015-05-01

    Full Text Available Oxidative damage to lipids and lipoproteins is implicated in the development of atherosclerotic vascular diseases, including peripheral artery disease (PAD. The paraoxonases (PON are a group of antioxidant enzymes, termed PON1, PON2, and PON3 that protect lipoproteins and cells from peroxidation and, as such, may be involved in protection against the atherosclerosis process. PON1 inhibits the production of chemokine (C–C motif ligand 2 (CCL2 in endothelial cells incubated with oxidized lipoproteins. PON1 and CCL2 are ubiquitously distributed in tissues, and this suggests a joint localization and combined systemic effect. The aim of the present study has been to analyze the quantitative immunohistochemical localization of PON1, PON3, CCL2 and CCL2 receptors in a series of patients with severe PAD. Portions of femoral and/or popliteal arteries from 66 patients with PAD were obtained during surgical procedures for infra-inguinal limb revascularization. We used eight normal arteries from donors as controls. PON1 and PON3, CCL2 and the chemokine-binding protein 2, and Duffy antigen/chemokine receptor, were increased in PAD patients. There were no significant changes in C–C chemokine receptor type 2. Our findings suggest that paraoxonases and chemokines play an important role in the development and progression of atherosclerosis in peripheral artery disease.

  15. PON1 L55M and Q192R gene polymorphisms and CAD risks in patients with hyperlipidemia : Clinical study of possible associations.

    Science.gov (United States)

    Chen, H; Ding, S; Zhou, M; Wu, X; Liu, X; Liu, J; Wu, Y; Liu, D

    2017-08-23

    A decreased plasma high density lipoprotein (HDL) cholesterol level is a strong risk factor for coronary artery disease (CAD). Antioxidant activity of HDL mainly lies in the activity of paraoxonase (PON). This study aimed to investigate the relationships between PON1 L55M and Q192R polymorphisms, and the risks of CAD in patients with hyperlipidemia. From January 2014 to January 2016, 244 patients were divided into hyperlipidemia, hyperlipidemia + CAD, and control groups. The hyperlipidemia and hyperlipidemia + CAD groups were designated as the case group. Serum PON1 concentrations were measured using the enzyme-linked immunosorbent assay. After isolating genomic DNA, the PON1 L55M and Q192R genes were amplified by polymerase chain reaction and sequenced. In the case group, the genotypes LM and LL were detected significantly more often than in the control group, as were the alleles R (33.33%, 42.12%) and L (22.78%, 29.11%). The frequency of QR and RR genotypes was significantly higher in the hyperlipidemia + CAD group than in the hyperlipidemia group; the allele R in the hyperlipidemia + CAD group (42.77%) was more frequent than in the hyperlipidemia group (23.78%). The Q192R polymorphism was associated with low serum PON1 concentrations, and the lowest concentration was observed in the 192QR + 192RR genotype (P = 0.03). Logistic regression analysis showed a significant correlation between the 192R allele and smoking (P = 0.03), body mass index (P = 0.02), systolic blood pressure (P = 0.004), total cholesterol (P = 0.03), triglycerides (P = 0.01), HDL (P = 0.004), and low density lipoprotein (P = 0.02). The PON1 alleles 192R and 55L are associated with CAD, and the Q192R polymorphism may be a risk factor for CAD.

  16. PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity.

    Science.gov (United States)

    Kim, Daniel Seung; Burt, Amber A; Ranchalis, Jane E; Vuletic, Simona; Vaisar, Tomas; Li, Wan-Fen; Rosenthal, Elisabeth A; Dong, Weijiang; Eintracht, Jason F; Motulsky, Arno G; Brunzell, John D; Albers, John J; Furlong, Clement E; Jarvik, Gail P

    2015-07-01

    Recent studies have failed to demonstrate a causal cardioprotective effect of HDL cholesterol levels, shifting focus to the functional aspects of HDL. Phospholipid transfer protein (PLTP) is an HDL-associated protein involved in reverse cholesterol transport. This study sought to determine the genetic and nongenetic predictors of plasma PLTP activity (PLTPa), and separately, to determine whether PLTPa predicted carotid artery disease (CAAD). PLTPa was measured in 1,115 European ancestry participants from a case-control study of CAAD. A multivariate logistic regression model was used to elucidate the relationship between PLTPa and CAAD. Separately, a stepwise linear regression determined the nongenetic clinical and laboratory characteristics that best predicted PLTPa. A final stepwise regression considering both nongenetic and genetic variables identified the combination of covariates that explained maximal PLTPa variance. PLTPa was significantly associated with CAAD (7.90 × 10(-9)), with a 9% decrease in odds of CAAD per 1 unit increase in PLTPa (odds ratio = 0.91). Triglyceride levels (P = 0.0042), diabetes (P = 7.28 × 10(-5)), paraoxonase 1 (PON1) activity (P = 0.019), statin use (P = 0.026), PLTP SNP rs4810479 (P = 6.38 × 10(-7)), and PCIF1 SNP rs181914932 (P = 0.041) were all significantly associated with PLTPa. PLTPa is significantly inversely correlated with CAAD. Furthermore, we report a novel association between PLTPa and PON1 activity, a known predictor of CAAD.

  17. PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity1[S

    Science.gov (United States)

    Kim, Daniel Seung; Burt, Amber A.; Ranchalis, Jane E.; Vuletic, Simona; Vaisar, Tomas; Li, Wan-Fen; Rosenthal, Elisabeth A.; Dong, Weijiang; Eintracht, Jason F.; Motulsky, Arno G.; Brunzell, John D.; Albers, John J.; Furlong, Clement E.; Jarvik, Gail P.

    2015-01-01

    Recent studies have failed to demonstrate a causal cardioprotective effect of HDL cholesterol levels, shifting focus to the functional aspects of HDL. Phospholipid transfer protein (PLTP) is an HDL-associated protein involved in reverse cholesterol transport. This study sought to determine the genetic and nongenetic predictors of plasma PLTP activity (PLTPa), and separately, to determine whether PLTPa predicted carotid artery disease (CAAD). PLTPa was measured in 1,115 European ancestry participants from a case-control study of CAAD. A multivariate logistic regression model was used to elucidate the relationship between PLTPa and CAAD. Separately, a stepwise linear regression determined the nongenetic clinical and laboratory characteristics that best predicted PLTPa. A final stepwise regression considering both nongenetic and genetic variables identified the combination of covariates that explained maximal PLTPa variance. PLTPa was significantly associated with CAAD (7.90 × 10−9), with a 9% decrease in odds of CAAD per 1 unit increase in PLTPa (odds ratio = 0.91). Triglyceride levels (P = 0.0042), diabetes (P = 7.28 × 10−5), paraoxonase 1 (PON1) activity (P = 0.019), statin use (P = 0.026), PLTP SNP rs4810479 (P = 6.38 × 10−7), and PCIF1 SNP rs181914932 (P = 0.041) were all significantly associated with PLTPa. PLTPa is significantly inversely correlated with CAAD. Furthermore, we report a novel association between PLTPa and PON1 activity, a known predictor of CAAD. PMID:26009633

  18. Potential association of paraoxonase-1, type 2 diabetes mellitus, and periodontitis.

    Science.gov (United States)

    Noack, Barbara; Aslanhan, Zeynep; Boué, Julia; Petig, Christin; Teige, Madlen; Schaper, Frank; Hoffmann, Thomas; Hannig, Christian

    2013-05-01

    The association between periodontitis and systemic diseases, including cardiovascular diseases and diabetes mellitus (DM), has been recognized repeatedly. Paraoxonase-1 (PON-1) is involved in the prevention of atherosclerosis, and decreased enzyme activity in patients with DM has been shown. The aim of this study is to investigate a possible correlation between decreased PON-1 activity and the association between impaired glucose metabolism or DM and periodontitis. PON-1 phenotype distribution and enzyme activities were characterized by measuring the hydrolysis of phenylacetate and paraoxon in serum samples of 87 patients with type 2 DM and 46 patients with pre-DM showing impaired fasting plasma glucose and/or impaired oral glucose tolerance. The control group comprised 64 individuals with normal fasting plasma glucose and normal glucose tolerance. Altogether, 154 study participants were available for complete clinical periodontal examination. No difference in periodontitis prevalence existed between the study groups. However, patients with DM had an increased risk of suffering from generalized periodontitis (adjusted odds ratio = 4.05; 95% confidence interval = 1.24 to 13.18; P = 0.02), and their PON-1 activity was reduced compared to controls. In contrast, patients with pre-DM showed neither an increased periodontitis risk nor an impaired paraoxonase status. PON-1 was not associated directly with periodontitis. Nevertheless, concerning patients with DM, poor oral hygiene, male sex, and PON-1 phenotype were found to be significant predictors for periodontitis extent. Type 2 DM, but not a prediabetic state, increases the risk of generalized periodontitis. PON-1 status in patients with type 2 DM may contribute to this association.

  19. Paraoxonase 1 activity and phenotype distribution in premenopausal and postmenopausal women

    Science.gov (United States)

    Butorac, Dražan; Ćelap, Ivana; Kačkov, Sanja; Robić, Vera; Miletić, Tomislav; Meštrić, Zlata Flegar; Hulina, Andrea; Kuna, Krunoslav; Grubišić, Tihana Žanić; Rajković, Marija Grdić

    2014-01-01

    Introduction Postmenopausal women have higher risk of cardiovascular disease. One of the contributing factors could be reduced activity of anti-atherogenic enzyme paraoxonase 1 (PON1). The aim of this study was to examine differences in the lipid status, paraoxonase and arylesterase PON1 activities and PON1 phenotype in women with regular menstrual cycle and in postmenopausal women. Materials and methods: The study included 51 women in reproductive age (25 in follicular and 26 in luteal phase of the menstrual cycle) and 23 women in postmenopause. Lipid parameters in sera were determined using original reagents and according to manufacturer protocol. PON1 activity in serum was assessed by spectrophotometric method with substrates: paraoxon and phenylacetate. PON1 phenotype was determined by double substrate method. Results: Compared to the women in follicular and luteal phase, postmenopausal women have significantly higher concentration of triglyceride [0.9 (0.7–1.3), 0.7 (0.6–1.0) vs. 1.5 (0.9–1.7) mmol/L; P = 0.002], cholesterol [5.10 (4.78–6.10), 5.05 (4.70–5.40) vs. 6.30 (5.73–7.23) mmol/L; P < 0.001], LDL [3.00 (2.56–3.63), 3.00 (2.70–3.70) vs. 3.90 (3.23–4.50) mmol/L; P < 0.001], and apolipoprotein B [0.88 (0.75–1.00), 0.79 (0.68–1.00) vs. 1.07 (0.90–1.24) mmol/L; P = 0.002]. PON1 basal [104 (66–260), 106 (63–250) vs. 93 (71–165) U/L; P = 0.847] and salt-stimulated paraoxonase activity [210 (131–462), 211 (120–442) vs. 180 (139–296) U/L; P = 0.857] as well as arylesterase activity [74 (63–82), 70 (54–91) vs. 70 (60–81) kU/L; P = 0.906] and PON1 phenotype (P = 0.810) were not different in the study groups. Conclusion: There are no differences in PON1 activity and PON1 phenotype between women with regular menstrual cycle and postmenopausal women. PMID:24969921

  20. Role of paraoxonase-1 in bone anabolic effects of parathyroid hormone in hyperlipidemic mice

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jinxiu [Department of Physiology, University of California, Los Angeles (United States); Cheng, Henry [Department of Medicine, University of California, Los Angeles (United States); Atti, Elisa [Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles (United States); Shih, Diana M. [Department of Medicine, University of California, Los Angeles (United States); Demer, Linda L. [Department of Physiology, University of California, Los Angeles (United States); Department of Medicine, University of California, Los Angeles (United States); Department of Bioengineering, University of California, Los Angeles (United States); Tintut, Yin, E-mail: ytintut@mednet.ucla.edu [Department of Medicine, University of California, Los Angeles (United States)

    2013-02-01

    Highlights: ► Anabolic effects of PTH were tested in hyperlipidemic mice overexpressing PON1. ► Expression of antioxidant regulatory genes was induced in PON1 overexpression. ► Bone resorptive activity was reduced in PON1 overexpressing hyperlipidemic mice. ► PON1 restored responsiveness to intermittent PTH in bones of hyperlipidemic mice. -- Abstract: Hyperlipidemia blunts anabolic effects of intermittent parathyroid hormone (PTH) on cortical bone, and the responsiveness to PTH are restored in part by oral administration of the antioxidant ApoA-I mimetic peptide, D-4F. To evaluate the mechanism of this rescue, hyperlipidemic mice overexpressing the high-density lipoprotein-associated antioxidant enzyme, paraoxonase 1 (Ldlr{sup −/−}PON1{sup tg}) were generated, and daily PTH injections were administered to Ldlr{sup −/−}PON1{sup tg} and to littermate Ldlr{sup −/−} mice. Expression of bone regulatory genes was determined by realtime RT-qPCR, and cortical bone parameters of the femoral bones by micro-computed tomographic analyses. PTH-treated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTH receptor (PTH1R), activating transcription factor-4 (ATF4), and osteoprotegerin (OPG) in femoral cortical bone, as well as significantly greater cortical bone mineral content, thickness, and area in femoral diaphyses compared with untreated Ldlr{sup −/−}PON1{sup tg} mice. In contrast, in control mice (Ldlr{sup −/−}) without PON1 overexpression, PTH treatment did not induce these markers. Calvarial bone of PTH-treated Ldlr{sup −/−}PON1{sup tg} mice also had significantly greater expression of osteoblastic differentiation marker genes as well as BMP-2-target and Wnt-target genes. Untreated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTHR1 than untreated Ldlr{sup −/−} mice, whereas sclerostin expression was reduced. In femoral cortical bones, expression levels of transcription factors, Fox

  1. Exploring the role of paraoxonases in the pathogenesis of coronary artery disease: a systematic review.

    Science.gov (United States)

    Abelló, David; Sancho, Elena; Camps, Jordi; Joven, Jorge

    2014-11-14

    Paraoxonases (PON) are three enzymes (PON1, PON2 and PON3) that play a role in the organism's antioxidant system; alterations in which are associated with diseases involving oxidative stress. In this review, we summarize the evidence of PON related to the pathogenesis of coronary artery disease (CAD) and atherosclerosis. We searched three electronic databases (PubMed, Scopus and Cochrane Database) with no date limit. All of the articles selected investigated PON enzymatic activity and/or PON gene polymorphisms. The selection focused on PON in relation to atherosclerosis, CAD and myocardial infarction. The exclusion criteria were a sample size PON1 enzymatic activity levels do influence atheroma formation. Conversely, relationships between PON2 and PON3 vs. CAD have not been extensively investigated. Our review of the current data concludes that the bases of paraoxonases involvement in atherosclerosis are poorly understood and that this issue requires future comprehensive, multi-centered studies.

  2. Exploring the role of paraoxonases in the pathogenesis of coronary artery disease: a systematic review.

    OpenAIRE

    David Abelló; Elena Sancho; Jordi Camps; Jorge Joven

    2014-01-01

    Paraoxonases (PON) are three enzymes (PON1, PON2 and PON3) that play a role in the organism’s antioxidant system; alterations in which are associated with diseases involving oxidative stress. In this review, we summarize the evidence of PON related to the pathogenesis of coronary artery disease (CAD) and atherosclerosis. We searched three electronic databases (PubMed, Scopus and Cochrane Database) with no date limit. All of the articles selected investigated PON enzymatic activity and/or PON...

  3. Replacement of dietary saturated fat with trans fat reduces serum paraoxonase activity in healthy men and women.

    Science.gov (United States)

    de Roos, Nicole M; Schouten, Evert G; Scheek, Leo M; van Tol, Arie; Katan, Martijn B

    2002-12-01

    A high intake of saturated fat and of trans isomers of unsaturated fat is associated with increased risk of cardiovascular disease. Recently, we found that replacement of saturated fat by trans fat in a dietary controlled study with 32 men and women decreased serum high-density lipoprotein (HDL)-cholesterol and impaired endothelial function, suggesting that trans fats have stronger adverse effects than saturated fats. To investigate this further, we measured the activity of serum paraoxonase (PON1) in serum samples of the same volunteers after consumption of both diets. PON1 protects lipoproteins from oxidative damage, and higher PON1 activity appears to be related to lower cardiovascular disease risk. PON1 activity (mean +/- SD) was 195.9 +/- 108.9 U/L after 4 weeks of consuming a diet with 22.9% of energy (en%) from saturated fat and 184.5 +/- 99.3 U/L when 9.3 en% from saturated fat was replaced by trans fat (P =.006). Thus, replacement of dietary saturated fat by trans fat not only decreased serum HDL-cholesterol and impaired endothelial function, but also decreased the activity of serum paraoxonase. Whether the changes in serum paraoxonase activity caused the changes in endothelial function needs to be further investigated.

  4. Paraoxonase 1 polymorphism and prenatal pesticide exposure associated with adverse cardiovascular risk profiles at school age.

    Directory of Open Access Journals (Sweden)

    Helle R Andersen

    Full Text Available BACKGROUND: Prenatal environmental factors might influence the risk of developing cardiovascular disease later in life. The HDL-associated enzyme paraoxonase 1 (PON1 has anti-oxidative functions that may protect against atherosclerosis. It also hydrolyzes many substrates, including organophosphate pesticides. A common polymorphism, PON1 Q192R, affects both properties, but a potential interaction between PON1 genotype and pesticide exposure on cardiovascular risk factors has not been investigated. We explored if the PON1 Q192R genotype affects cardiovascular risk factors in school-age children prenatally exposed to pesticides. METHODS: Pregnant greenhouse-workers were categorized as high, medium, or not exposed to pesticides. Their children underwent a standardized examination at age 6-to-11 years, where blood pressure, skin folds, and other anthropometric parameters were measured. PON1-genotype was determined for 141 children (88 pesticide exposed and 53 unexposed. Serum was analyzed for insulin-like growth factor I (IGF-I, insulin-like growth factor binding protein 3 (IGFBP3, insulin and leptin. Body fat percentage was calculated from skin fold thicknesses. BMI results were converted to age and sex specific Z-scores. RESULTS: Prenatally pesticide exposed children carrying the PON1 192R-allele had higher abdominal circumference, body fat content, BMI Z-scores, blood pressure, and serum concentrations of leptin and IGF-I at school age than unexposed children. The effects were related to the prenatal exposure level. For children with the PON1 192QQ genotype, none of the variables was affected by prenatal pesticide exposure. CONCLUSION: Our results indicate a gene-environment interaction between prenatal pesticide exposure and the PON1 gene. Only exposed children with the R-allele developed adverse cardiovascular risk profiles thought to be associated with the R-allele.

  5. Paraoxonase 1 Polymorphism and Prenatal Pesticide Exposure Associated with Adverse Cardiovascular Risk Profiles at School Age

    Science.gov (United States)

    Andersen, Helle R.; Wohlfahrt-Veje, Christine; Dalgård, Christine; Christiansen, Lene; Main, Katharina M.; Nellemann, Christine; Murata, Katsuyuki; Jensen, Tina K.; Skakkebæk, Niels E.; Grandjean, Philippe

    2012-01-01

    Background Prenatal environmental factors might influence the risk of developing cardiovascular disease later in life. The HDL-associated enzyme paraoxonase 1 (PON1) has anti-oxidative functions that may protect against atherosclerosis. It also hydrolyzes many substrates, including organophosphate pesticides. A common polymorphism, PON1 Q192R, affects both properties, but a potential interaction between PON1 genotype and pesticide exposure on cardiovascular risk factors has not been investigated. We explored if the PON1 Q192R genotype affects cardiovascular risk factors in school-age children prenatally exposed to pesticides. Methods Pregnant greenhouse-workers were categorized as high, medium, or not exposed to pesticides. Their children underwent a standardized examination at age 6-to-11 years, where blood pressure, skin folds, and other anthropometric parameters were measured. PON1-genotype was determined for 141 children (88 pesticide exposed and 53 unexposed). Serum was analyzed for insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP3), insulin and leptin. Body fat percentage was calculated from skin fold thicknesses. BMI results were converted to age and sex specific Z-scores. Results Prenatally pesticide exposed children carrying the PON1 192R-allele had higher abdominal circumference, body fat content, BMI Z-scores, blood pressure, and serum concentrations of leptin and IGF-I at school age than unexposed children. The effects were related to the prenatal exposure level. For children with the PON1 192QQ genotype, none of the variables was affected by prenatal pesticide exposure. Conclusion Our results indicate a gene-environment interaction between prenatal pesticide exposure and the PON1 gene. Only exposed children with the R-allele developed adverse cardiovascular risk profiles thought to be associated with the R-allele. PMID:22615820

  6. The inverse association of HDL-cholesterol with future risk of hypertension is not modified by its antioxidant constituent, paraoxonase-1 : The PREVEND prospective cohort study

    NARCIS (Netherlands)

    Kunutsor, Setor K; Kieneker, Lyanne M; Bakker, Stephan J L; James, Richard W; Dullaart, Robin P F

    BACKGROUND AND AIMS: High-density lipoprotein cholesterol (HDL-C), an established risk marker for atherosclerotic cardiovascular disease (CVD), has been shown to be inversely and independently associated with incident hypertension. Paraoxonase-1 (PON-1) is an HDL-bound esterase enzyme associated

  7. Serum paraoxonase 1 activity in patients with iron deficiency anemia

    Science.gov (United States)

    Gedikbasi, Asuman; Akalin, Nilgul; Gunaldi, Meral; Yilmaz, Deniz; Mert, Meral; Harmankaya, Ozlem; Soylu, Aliye; Karakaya, Pinar; Kumbasar, Abdulbaki

    2016-01-01

    Introduction In this study we aimed to detect paraoxonase 1 (PON-1) activity in iron deficiency anemia (IDA) and to compare it with healthy controls by observing the change after iron therapy. Material and methods In this study, 50 adult patients with IDA and 40 healthy subjects were enrolled. All patients were analyzed at the beginning and after treatment according to laboratory assessments. Results Mean paraoxonase and arylesterase activities in the iron deficiency anemia group were significantly lower than mean activities of the control group (102.4 ±19.2 U/l and 163.3 ±13.68 U/l, respectively and 157.3 ±26.4 U/l and 256.1 ±24.6 U/l, respectively; p = 0.0001 for both). Paraoxonase and arylesterase activities significantly increased after treatment for IDA (143.2 ±13.9 and 197.6 ±27.9 U/l, respectively, p = 0.0001). Mean activities after treatment with iron were significantly lower than mean activities in the control group (p = 0.002; p = 0.0001 respectively). Conclusions Paraoxonase and arylesterase activities in patients with IDA significantly increased after treatment with iron therapy. In adults IDA may also be one of the factors associated with increased risk of atherosclerosis. PMID:27478448

  8. Paraoxonase-1 activity is positively related to phospholipid transfer protein activity in type 2 diabetes mellitus: Role of large HDL particles.

    Science.gov (United States)

    Dullaart, Robin P F; Gruppen, Eke G; Dallinga-Thie, Geesje M

    2016-04-01

    High density lipoprotein (HDL)-associated paraoxonase-1 (PON-1) exerts anti-oxidative properties, whereas phospholipid transfer protein (PLTP) is able to convert mature HDL into larger and smaller HDL particles. Here we tested associations of PON-1 with PLTP in type 2 diabetes mellitus (T2DM), a condition characterized by lower PON-1 activity and higher PLTP activity. Serum PON-1 (arylesterase activity), plasma PLTP activity (liposome-vesicle HDL system), and (apo)lipoproteins were measured in 81 T2DM subjects (mean age 59±9years; 31 women; no insulin treatment). In 48 participants, HDL subfractions were measured by nuclear magnetic resonance spectroscopy. In univariate correlation analysis, PON-1 activity was positively related to PLTP activity (r=0.348, p=0.001). PLTP activity was positively related to blood pressure, body mass index and triglycerides, whereas PON-1 activity was positively to HDL cholesterol and apoA-I (p<0.05 to <0.01 for each). Both PLTP activity and PON-I activity were positively related to large HDL particles (r=0.379, p=0.008 and r=0.411, p=0.004, respectively). In multivariable linear regression analysis, PON-1 activity was associated with PLTP activity independent of clinical covariates and HDL cholesterol or apoA-I (β=0.340, p=0.001 and β=0.320, p=0.003, respectively). The association of PON-1 activity with PLTP activity was lost in analysis which included large HDL particles (large HDL: β=0.411, p=0.004). PON-1 activity is positively related to PLTP activity in T2DM, raising the possibility that PLTP could act to maintain PON-1. This association may in part be attributable to a common relationship of PON-1 and PLTP with large HDL particles. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  9. Lack of ligand-selective binding of the aryl hydrocarbon receptor to putative DNA binding sites regulating expression of Bax and paraoxonase 1 genes.

    Science.gov (United States)

    DeGroot, Danica E; Hayashi, Ai; Denison, Michael S

    2014-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates the biological and toxicological effects of structurally diverse chemicals through its ability to bind specific DNA recognition sites (dioxin responsive elements (DREs)), and activate transcription of adjacent genes. While the DRE has a highly conserved consensus sequence, it has been suggested that the nucleotide specificity of AhR DNA binding may be ligand-dependent. The upstream regulatory regions of the murine Bax and human paraoxonase 1 (PON1) genes reportedly contain unique DRE-like sequences that respond to AhRs activated by some ligands but not others. Given the significant implications of this observation to understanding the diversity in AhR responses and that of other ligand-dependent nuclear receptors, a combination of DNA binding, nuclear translocation and gene expression analysis was used to investigate the molecular mechanisms underlying these ligand-selective responses. Although known AhR agonists stimulated AhR nuclear translocation, DRE binding and gene expression, the ligand-selective DRE-like DNA elements identified in the Bax and PON1 upstream regulatory regions failed to bind ligand-activated AhR or confer AhR-responsiveness upon a reporter gene. These results argue against the reported ligand-selectivity of AhR DNA binding and suggest DNA binding by ligand activated AhR involves DRE-containing DNA.

  10. Paraoxonase-1 is not a major determinant of stent thrombosis in a Taiwanese population.

    Directory of Open Access Journals (Sweden)

    Dong-Yi Chen

    Full Text Available BACKGROUND: Clopidogrel is a prodrug that undergoes in vivo bioactivation to show its antiplatelet effects. Recent studies have shown that cytochrome P450 (CYP, ATP-binding cassette transporters (ABCB1, and paraoxonase-1 (PON1 play crucial roles in clopidogrel bioactivation. Here, we aim to determine the effects of genetic polymorphisms of CYP (CYP 2C19*2, CYP 2C19*3, and CYP 2C19*17, ABCB1 (ABCB1 3435C>T, ABCB1 129T>C, and ABCB1 2677G>T/A, and PON1 (PON1 Q192R, PON1 L55M, and PON1 108C>T on the development of stent thrombosis (ST in patients receiving clopidogrel after percutaneous coronary intervention (PCI. METHODS AND RESULTS: We evaluated the incidence of ST (0.64% in 4964 patients who were recruited in the CAPTAIN registry (Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions. The presence of genetic polymorphisms was assessed in 20 subjects who developed ST after aspirin and clopidogrel therapy and in 40 age- and sex-matched control subjects who did not develop ST, which was documented after 9 months of angiographic follow-up. ST was acute in 5 subjects, subacute in 7, late in 7, and very late in 1. The presence of CYP 2C19*2 allele was significantly associated with ST (adjusted odds ratio [ORadj]: 4.20, 95% confidence interval [CI], 1.263-9.544; P = 0.031. However, genetic variations in PON1 and ABCB1 showed no significant association with ST. CONCLUSION: We conclude that in a Taiwanese population, PON1 Q192R genotype is not associated with ST development after PCI. However, the presence of CYP 2C19*2 allele is a risk factor for ST development after PCI.

  11. Interaction between paraoxonase 1 polymorphism and prenatal pesticide exposure on metabolic markers in children using a multiplex approach

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Nellemann, Christine; Wohlfahrt-Veje, Christine;

    2015-01-01

    Prenatal environmental exposures may influence the risk of cardio-metabolic diseases later in life. This study used a multiplex approach to investigate non-fasting serum levels of metabolic markers in a cohort of school-aged children for whom associations between prenatal pesticide exposure...... and body fat content and blood pressure were previously found to be dependent on paraoxonase1 (PON1) Q192R genotype. In children with the PON1 192 R-allele, leptin, glucagon, and plasminogen activator inhibitor-1 (PAI-1) were positively associated with prenatal pesticide exposure. For PON1 192 QQ......-homozygote children none of the biomarkers were significantly affected by prenatal pesticide exposure. In children with the R-allele, leptin was associated with both body fat measures and prenatal pesticide exposure and seems to mediate body fat accumulation in exposed children. These findings support our previous...

  12. Serum paraoxonase-1 activity is more closely related to HDL particle concentration and large HDL particles than to HDL cholesterol in Type 2 diabetic and non-diabetic subjects

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Otvos, James D.; James, Richard W.

    2014-01-01

    Objectives: We determined relationships of the anti-oxidative enzyme, paraoxonase-1 (PON-1), with high density lipoprotein (HDL) subfractions, and tested whether these relationships are stronger than those with HDL cholesterol and apolipoprotein A-I (apoA-I) in subjects with and without type 2 diabe

  13. Serum paraoxonase-1 activity is more closely related to HDL particle concentration and large HDL particles than to HDL cholesterol in Type 2 diabetic and non-diabetic subjects

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Otvos, James D.; James, Richard W.

    Objectives: We determined relationships of the anti-oxidative enzyme, paraoxonase-1 (PON-1), with high density lipoprotein (HDL) subfractions, and tested whether these relationships are stronger than those with HDL cholesterol and apolipoprotein A-I (apoA-I) in subjects with and without type 2

  14. Both paraoxonase-1 genotype and activity do not predict the risk of future coronary artery disease; the EPIC-Norfolk Prospective Population Study.

    Directory of Open Access Journals (Sweden)

    Rakesh S Birjmohun

    Full Text Available BACKGROUND: Paraoxonase-1 (PON1 is an antioxidant enzyme, that resides on high-density lipoprotein (HDL. PON1-activity, is heavily influenced by the PON1-Q192R polymorphism. PON1 is considered to protect against atherosclerosis, but it is unclear whether this relation is independent of its carrier, HDL. In order to evaluate the atheroprotective potential of PON1, we assessed the relationships among PON1-genotype, PON1-activity and risk of future coronary artery disease (CAD, in a large prospective case-control study. METHODOLOGY/PRINCIPAL FINDINGS: Cases (n = 1138 were apparently healthy men and women aged 45-79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n = 2237 were matched by age, sex and enrollment time. PON1-activity was similar in cases and controls (60.7+/-45.3 versus 62.6+/-45.8 U/L, p = 0.3 and correlated with HDL-cholesterol levels (r = 0.16, p<0.0001. The PON1-Q192R polymorphism had a profound impact on PON1-activity, but did not predict CAD risk (Odds Ratio [OR] per R allele 0.98[0.84-1.15], p = 0.8. Using conditional logistic regression, quartiles of PON1-activity showed a modest inverse relation with CAD risk (OR for the highest versus the lowest quartile 0.77[0.63-0.95], p = 0.01; p-trend = 0.06. PON1-activity adjusted for Q192R polymorphism correlated better with HDL-cholesterol (r = 0.26, p<0.0001 and more linearly predicted CAD risk (0.79[0.64-0.98], p = 0.03; p-trend = 0.008. However, these relationships were abolished after adjustment for HDL (particles-cholesterol-size and apolipoproteinA-I (0.94[0.74-1.18], p-trend = 0.3. CONCLUSIONS/SIGNIFICANCE: This study, shows that PON1-activity inversely relates to CAD risk, but not independent of HDL, due to its close association with the HDL-particle. These data strongly suggest that a low PON1-activity is not a causal factor in atherogenesis.

  15. Effect of Quercetin on Paraoxonase 2 Levels in RAW264.7 Macrophages and in Human Monocytes—Role of Quercetin Metabolism

    Directory of Open Access Journals (Sweden)

    Manfred James Mueller

    2009-09-01

    Full Text Available There is increasing evidence that the intracellular antioxidant enzyme paraoxonase 2 (PON2 may have a protective function in the prevention of atherogenesis. An enhancement of PON2 activity by dietary factors including flavonoids is therefore of interest. In the present study we determined the effect of quercetin on paraoxonase 2 levels in cultured murine macrophages in vitro and in overweight subjects with a high cardiovascular risk phenotype supplemented with 150 mg quercetin/day for 42 days in vivo. Supplementation of murine RAW264.7 macrophages in culture with increasing concentrations of quercetin (1, 10, 20 μmol/L resulted in a significant increase in PON2 mRNA and protein levels, as compared to untreated controls. Unlike quercetin, its glucuronidated metabolite quercetin-3-glucuronide did not affect PON2 gene expression in cultured macrophages. However the methylated quercetin derivative isorhamnetin enhanced PON2 gene expression in RAW264.7 cells to similar extent like quercetin. Although supplementing human volunteers with quercetin was accompanied by a significant increase in plasma quercetin concentration, dietary quercetin supplementation did not change PON2 mRNA levels in human monocytes in vivo. Current data indicate that quercetin supplementation increases PON2 levels in cultured monocytes in vitro but not in human volunteers in vivo.

  16. Role of genetic polymorphisms of CYP1A1, CYP3A5, CYP2C9, CYP2D6, and PON1 in the modulation of DNA damage in workers occupationally exposed to organophosphate pesticides

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Satyender [Division of Biochemistry and Biotechnology, National Centre for Disease Control 22, Sham Nath Marg, Delhi-110054 (India); Kumar, Vivek [Environmental Biochemistry and Molecular Biology laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital, University of Delhi, Dilshad Garden, Delhi-110095 (India); Vashisht, Kapil; Singh, Priyanka [Division of Biochemistry and Biotechnology, National Centre for Disease Control 22, Sham Nath Marg, Delhi-110054 (India); Banerjee, Basu Dev, E-mail: banerjeebd@hotmail.com [Environmental Biochemistry and Molecular Biology laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital, University of Delhi, Dilshad Garden, Delhi-110095 (India); Rautela, Rajender Singh; Grover, Shyam Sunder; Rawat, Devendra Singh; Pasha, Syed Tazeen [Division of Biochemistry and Biotechnology, National Centre for Disease Control 22, Sham Nath Marg, Delhi-110054 (India); Jain, Sudhir Kumar [Centre for Epidemiology and Parasitic Diseases, National Centre for Disease Control 22, Sham Nath Marg, Delhi-110054 (India); Rai, Arvind [Division of Biochemistry and Biotechnology, National Centre for Disease Control 22, Sham Nath Marg, Delhi-110054 (India)

    2011-11-15

    Organophosphate pesticides (OPs) are primarily metabolized by several xenobiotic metabolizing enzymes (XMEs). Very few studies have explored genetic polymorphisms of XMEs and their association with DNA damage in pesticide-exposed workers. The present study was designed to determine the role of genetic polymorphisms of CYP1A1, CYP3A5, CYP2C9, CYP2D6, and PON1 in the modulation of DNA damage in workers occupationally exposed to OPs. We examined 284 subjects including 150 workers occupationally exposed to OPs and 134 normal healthy controls. The DNA damage was evaluated using the alkaline comet assay and genotyping was done using PCR-RFLP. The results revealed that the PONase activity toward paraoxonase and AChE activity was found significantly lowered in workers as compared to control subjects (p < 0.001). Workers showed significantly higher DNA damage compared to control subjects (14.37 {+-} 2.15 vs. 6.24 {+-} 1.37 tail% DNA, p < 0.001). Further, the workers with CYP2D6*3 PM and PON1 (QQ and MM) genotypes were found to have significantly higher DNA damage when compared to other genotypes (p < 0.05). In addition, significant increase in DNA damage was also observed in workers with concomitant presence of certain CYP2D6 and PON1 (Q192R and L55M) genotypes which need further extensive studies. In conclusion, the results indicate that the PON1 and CYP2D6 genotypes can modulate DNA damage elicited by some OPs possibly through gene-environment interactions. -- Highlights: Black-Right-Pointing-Pointer Role of CYP1A1, CYP3A5, CYP2C, CYP2D6 and PON1 genotypes on DNA damage. Black-Right-Pointing-Pointer Workers exposed to some OPs demonstrated increased DNA damage. Black-Right-Pointing-Pointer CYP2D6 *3 PM and PON1 (Q192R and L55M) genotypes are associated with DNA damage. Black-Right-Pointing-Pointer Concomitant presence of certain CYP2D6 and PON1 genotypes can increase DNA damage.

  17. The Search for Dietary Supplements to Elevate or Activate Circulating Paraoxonases

    Science.gov (United States)

    Lou-Bonafonte, José M.; Gabás-Rivera, Clara; Navarro, María A.; Osada, Jesús

    2017-01-01

    Low levels of paraoxonase 1 (PON1) have been associated with the development of several pathological conditions, whereas high levels have been shown to be anti-atherosclerotic in mouse models. These findings suggest that PON1 could be a good surrogate biomarker. The other members of the family, namely PON2 and PON3, the role of which has been much less studied, deserve more attention. This paper provides a systematic review of current evidence concerning dietary supplements in that regard. Preliminary studies indicate that the response to dietary supplements may have a nutrigenetic aspect that will need to be considered in large population studies or in clinical trials. A wide range of plant preparations have been found to have a positive action, with pomegranate and some of its components being the best characterized and Aronia melanocarpa one of the most active. Flavonoids are found in the composition of all active extracts, with catechins and genistein being the most promising agents for increasing PON1 activity. However, some caveats regarding the dose, length of treatment, bioavailability, and stability of these compounds in formulations still need to be addressed. Once these issues have been resolved, these compounds could be included as nutraceuticals and functional foods capable of increasing PON1 activity, thereby helping with the long-term prevention of atherosclerosis and other chronic ailments. PMID:28212288

  18. Paraoxonase and Arylesterase Activities, Lipid Profile, and Oxidative Damage in Experimental Ischemic Colitis Model

    Directory of Open Access Journals (Sweden)

    Ethem Unal

    2012-01-01

    Full Text Available Objective. In the present study, since PON1 is known as an HDL-associated antioxidant enzyme that inhibits the oxidative modification of LDL and oxidative stress plays a role in the pathogenesis of mesenteric ischemia, we investigated the changes in PON1 activity and lipid profile in an experimental ischemic colitis model. Methods. Forty male Wistar albino rats were divided into two groups: the control group (N=15 and the experimental group (N=25. All animals were anesthetized with ether and ketamine anesthesia to undergo a midline laparotomy. Ischemic colitis was induced by marginal vessel ligation in the splenic flexura (devascularization process. A sham laparotomy was performed in the control group. All animals were sacrificed on the seventh postoperative day. Oxidative stress marker (malonyldialdehyde, MDA, lipid profile, and paraoxonase (PON-1 and arylesterase activities were determined. Histopathological evaluation was done under light microscopy, after sectioning and staining with hematoxyline and eosin. Statistical analysis was conducted using Student’s t-test and Mann-Whitney U test, and P0.05. Conclusions. PON1 and arylesterase play an important role in the pathophysiology of ischemic colitis.

  19. Plasma paraoxonase, oxidative status level, and their relationship with asthma control test in children with asthma.

    Science.gov (United States)

    Emin, O; Hasan, A; Rusen, D M

    2015-01-01

    Assessment of asthma with a control test has been suggested as a relevant approach in recent years. However, no biomarker of systemic inflammation has been included in the assessment of asthma control. To evaluate plasma paraoxonase (PON1), total oxidant status (TOS), and total antioxidant status (TAS) levels in children with asthma according to the disease control, and the performance in the identification of uncontrolled patients. Stable asthmatic children (n=85) and healthy controls (n=55) were recruited for this study. Blood samples were collected for plasma PON1, TOS, and TAS measurements. Any contributing factors that may affect plasma PON1, TAS, and TOS levels were excluded from both groups. The diagnostic potential of these measures was evaluated using receiver operating characteristic (ROC) analysis. Comparing the asthmatic children with the control group, plasma TAS and TOS levels were significantly higher (TAS; 6.9 ± 2.1, 1.05 ± 0.32, Pasthma, respectively. Asthma Control Test (ACT) presented an AUC of 0.972 for the identification of uncontrolled asthma. PON1 and TOS levels may be systemic markers of uncontrolled asthma in children. Combined use of these two biomarkers with asthma control test may identify patients with uncontrolled asthma in children. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  20. The Search for Dietary Supplements to Elevate or Activate Circulating Paraoxonases.

    Science.gov (United States)

    Lou-Bonafonte, José M; Gabás-Rivera, Clara; Navarro, María A; Osada, Jesús

    2017-02-15

    Low levels of paraoxonase 1 (PON1) have been associated with the development of several pathological conditions, whereas high levels have been shown to be anti-atherosclerotic in mouse models. These findings suggest that PON1 could be a good surrogate biomarker. The other members of the family, namely PON2 and PON3, the role of which has been much less studied, deserve more attention. This paper provides a systematic review of current evidence concerning dietary supplements in that regard. Preliminary studies indicate that the response to dietary supplements may have a nutrigenetic aspect that will need to be considered in large population studies or in clinical trials. A wide range of plant preparations have been found to have a positive action, with pomegranate and some of its components being the best characterized and Aronia melanocarpa one of the most active. Flavonoids are found in the composition of all active extracts, with catechins and genistein being the most promising agents for increasing PON1 activity. However, some caveats regarding the dose, length of treatment, bioavailability, and stability of these compounds in formulations still need to be addressed. Once these issues have been resolved, these compounds could be included as nutraceuticals and functional foods capable of increasing PON1 activity, thereby helping with the long-term prevention of atherosclerosis and other chronic ailments.

  1. The Search for Dietary Supplements to Elevate or Activate Circulating Paraoxonases

    Directory of Open Access Journals (Sweden)

    José M. Lou-Bonafonte

    2017-02-01

    Full Text Available Low levels of paraoxonase 1 (PON1 have been associated with the development of several pathological conditions, whereas high levels have been shown to be anti-atherosclerotic in mouse models. These findings suggest that PON1 could be a good surrogate biomarker. The other members of the family, namely PON2 and PON3, the role of which has been much less studied, deserve more attention. This paper provides a systematic review of current evidence concerning dietary supplements in that regard. Preliminary studies indicate that the response to dietary supplements may have a nutrigenetic aspect that will need to be considered in large population studies or in clinical trials. A wide range of plant preparations have been found to have a positive action, with pomegranate and some of its components being the best characterized and Aronia melanocarpa one of the most active. Flavonoids are found in the composition of all active extracts, with catechins and genistein being the most promising agents for increasing PON1 activity. However, some caveats regarding the dose, length of treatment, bioavailability, and stability of these compounds in formulations still need to be addressed. Once these issues have been resolved, these compounds could be included as nutraceuticals and functional foods capable of increasing PON1 activity, thereby helping with the long-term prevention of atherosclerosis and other chronic ailments.

  2. Does metformin increase paraoxonase activity in patients with the metabolic syndrome? Additional data from the MEFISTO study.

    Science.gov (United States)

    Meaney, Eduardo; Sierra-Vargas, Patricia; Meaney, Alejandra; Guzmán-Grenfell, Martín; Ramírez-Sánchez, Israel; Hicks, Juan Jose; Olivares-Corichi, Ivonne; Ceballos, Guillermo

    2012-06-01

    In a subanalysis on the metformin, arterial function, intima-media thickness, and nitroxidation in the metabolic syndrome (MEFISTO)(8) (an open-label fashion, with 1 year of 850 mg daily of metformin) subjects' samples, we measured the paraoxonase 1 (PON1) activity in 39 patients that finished the study and relate values with high density lipoprotein (HDL). The comparative PON1 activities at the beginning and at the end of the study were 5.528 ± 0.588 and 4.743 ± 0.619 nmol/mg protein/min (NS) for control group and 3.229 ± 0.403 and 5.135 ± 0.585 nmol/mg protein/min (p < 0.02) for the metformin group. Our data showed an enhance of PON1 activity in patients with metabolic syndrome treated with metformin, although in them, the raise of HDL concentration was less than control patients, suggesting that the increase in quality (measured here as PON1 activity) could be at least as important as an increase in its concentration. Our results point out that there is a relationship among PON1 activity and the reduction of carotideal intima-media thickness.

  3. Role of genetic polymorphisms of CYP1A1, CYP3A5, CYP2C9, CYP2D6, and PON1 in the modulation of DNA damage in workers occupationally exposed to organophosphate pesticides.

    Science.gov (United States)

    Singh, Satyender; Kumar, Vivek; Vashisht, Kapil; Singh, Priyanka; Banerjee, Basu Dev; Rautela, Rajender Singh; Grover, Shyam Sunder; Rawat, Devendra Singh; Pasha, Syed Tazeen; Jain, Sudhir Kumar; Rai, Arvind

    2011-11-15

    Organophosphate pesticides (OPs) are primarily metabolized by several xenobiotic metabolizing enzymes (XMEs). Very few studies have explored genetic polymorphisms of XMEs and their association with DNA damage in pesticide-exposed workers. The present study was designed to determine the role of genetic polymorphisms of CYP1A1, CYP3A5, CYP2C9, CYP2D6, and PON1 in the modulation of DNA damage in workers occupationally exposed to OPs. We examined 284 subjects including 150 workers occupationally exposed to OPs and 134 normal healthy controls. The DNA damage was evaluated using the alkaline comet assay and genotyping was done using PCR-RFLP. The results revealed that the PONase activity toward paraoxonase and AChE activity was found significantly lowered in workers as compared to control subjects (pdamage compared to control subjects (14.37±2.15 vs. 6.24±1.37 tail% DNA, pdamage when compared to other genotypes (pdamage was also observed in workers with concomitant presence of certain CYP2D6 and PON1 (Q192R and L55M) genotypes which need further extensive studies. In conclusion, the results indicate that the PON1 and CYP2D6 genotypes can modulate DNA damage elicited by some OPs possibly through gene-environment interactions. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Paraoxonase 1 Polymorphism and Prenatal Pesticide Exposure Associated with Adverse Cardiovascular Risk Profiles at School Age

    DEFF Research Database (Denmark)

    Andersen, Helle R.; Wohlfahrt-Veje, Christine; Dalgard, Christine

    2012-01-01

    Background: Prenatal environmental factors might influence the risk of developing cardiovascular disease later in life. The HDL-associated enzyme paraoxonase 1 (PON1) has anti-oxidative functions that may protect against atherosclerosis. It also hydrolyzes many substrates, including organophosphate...... prenatally exposed to pesticides. Methods: Pregnant greenhouse-workers were categorized as high, medium, or not exposed to pesticides. Their children underwent a standardized examination at age 6-to-11 years, where blood pressure, skin folds, and other anthropometric parameters were measured. PON1-genotype...... was determined for 141 children (88 pesticide exposed and 53 unexposed). Serum was analyzed for insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP3), insulin and leptin. Body fat percentage was calculated from skin fold thicknesses. BMI results were converted to age and sex...

  5. Incident type 2 diabetes is associated with HDL, but not with its anti-oxidant constituent - paraoxonase-1: The prospective cohort PREVEND study.

    Science.gov (United States)

    Kunutsor, Setor K; Kieneker, Lyanne M; Bakker, Stephan J L; James, Richard W; Dullaart, Robin P F

    2017-08-01

    High-density lipoprotein cholesterol (HDL-C) is an established risk marker for cardiovascular disease and consistently associated with type 2 diabetes risk. Serum paraoxonase-1 (PON-1) - an anti-oxidant constituent of HDL - is inversely associated with cardiovascular disease risk, but its relationship with incident type 2 diabetes is uncertain. We aimed to investigate the prospective association between PON-1 and type 2 diabetes risk. PON-1 was measured as its arylesterase activity at baseline in the Prevention of Renal and Vascular End-stage Disease (PREVEND) prospective study of 5947 predominantly Caucasian participants aged 28-75years with no pre-existing diabetes, that recorded 500 type 2 diabetes cases during a median follow-up of 11.2years. Serum PON-1 was positively correlated with HDL-C (r=0.17; PHDL-C (1.05 (0.96 to 1.15; P=0.29). However, in subsidiary analyses in the same set of participants, serum HDL-C concentration was inversely and independently associated with risk of type 2 diabetes. Incident type 2 diabetes is associated with HDL cholesterol but not with its anti-oxidant constituent - PON-1 - in a large cohort of apparently healthy men and women. The current data question the importance of PON-1 activity for the development of diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Interaction effects between Paraoxonase 1 variants and cigarette smoking on risk of coronary heart disease in a Singaporean Chinese population.

    Science.gov (United States)

    Han, Yi; Dorajoo, Rajkumar; Ke, Tingjing; Ayala, Burger; Chang, Xuling; Khor, Chiea-Chuen; van Dam, Rob M; Yuan, Jian-Min; Koh, Woon-Puay; Liu, Jianjun; Goh, Daniel Y T; Friedlander, Yechiel; Heng, Chew-Kiat

    2015-05-01

    Paraoxonase 1 (PON1) plays an important role in reducing the risk of coronary heart disease (CHD). Smoking is known to reduce PON1 activity. We aimed to investigate the effects of interactions between PON1 variants and smoking on CHD in the Singaporean Chinese population. In a case-control study nested within Singapore Chinese Health Study (N=1914), subjects with and without CHD were classified into never-smokers and ever-smokers (ever smoked at least one cigarette a day for 1 year or longer). Associations at four independent SNPs at the PON1 locus (rs3735590, rs3917550, rs662, rs3917481) with CHD were evaluated using logistic regression, before/after stratification on smoking status. Interactions between smoking and PON1 variants were analyzed with likelihood ratio tests, by including the SNP*smoking interaction term in regression analyses. The T allele at the coding SNP, rs662, was associated with higher risk of CHD in ever-smokers only (OR=1.35, 95% CI 1.08-1.68; adjusted P=0.036). At the miR-SNP, rs3735590, carrying at least one copy of minor allele T was associated with increased risk of CHD in a dominant manner in never-smokers only (OR=1.53, 95% CI 1.11-2.11; adjusted P=0.036). Significant interactions between two PON1 SNPs and smoking in relation to CHD risk were identified (adjusted P=0.012 for rs662; adjusted P=0.044 for rs3735590). These associations remained significant after adjustment for known CHD risk factors and upon correction for multiple tests. Two PON1 SNPs, rs662 and rs3735590, were found to significantly interact with cigarette smoking to modulate the risk of CHD in the Singaporean Chinese population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Correlation between PON1 gene polymorphisms and breast cancer risk: a Meta-analysis

    OpenAIRE

    Wen, Yayuan; Huang, Zemin; Zhang, Xiaohua; Gao, Bo; He, Yujun

    2015-01-01

    Objective: A number of studies have investigated the relationship between the PON1 gene polymorphisms and breast cancer risk, but the conclusions are not consistent. In this paper, a meta-analysis was conducted to explore the possible reasons for these inconsistencies, expecting to further clarify the correlation between PON1 gene polymorphisms and breast cancer risk. Methods: After searches in the database such as MEDLINE, EBSCO, ProQuest, Google Scholar, High-Wire, SID (Scientific Informati...

  8. Atorvastatin effects on liver enzymes, antioxidant content and paraoxonase 1: An animal trial study

    Directory of Open Access Journals (Sweden)

    Pegah Barzegar,

    2016-06-01

    Full Text Available Background: Liver cirrhosis (LC is end-stage and irreversible phase of some chronic liver diseases. Treatment of cirrhosis is varied. Statins are one of them for prophylactic use, and several studies have shown their usefulness and effectiveness in control of LC but according to some other studies the use of Atorvastatin is now matter of discuss. Many studies reported the role of statins in increased activity of PON1 in patients with hyperlipoproteinemia. This study aims to evaluate the effect of atorvastatin on PON1 activities on development of liver cirrhosis in animal models of mice with ligated bile duct. Material and methods:The 32 rats were haphazardly partitioned On two groups: sham group and Bile duct ligated (BDL group. Each group was also divided in two subgroups in order to treat with either atorvastatin 15 mg/kg suspended in 5%CMC (Sigma Chemicals Co., USA or the same volume/weight of the 5% CMC vehicle for 28 days. At the end of the 4-week period, blood samples were collected by puncturing the heart under deep anesthesia and laboratory test for blood was operated. All statistical analyses were carried out using Prism statistical software .These differences were considered significant when probability was less than 0.05. Results: BDL decreased paraoxonase activities and increase MDA and liver enzymes while atorvastatin treatment increase PON1 activity and decreased MDA levels and liver enzymes. Conclusion: These data confirm activity of atorvastatin in cirrhosis probably by its ability of prevention reducing paraoxonase 1 activity. Conclusion: These data confirm the antioxidant activity of atorvastatin in cirrhosis probably by its ability of prevention reducing paraoxonase 1 activity and expression

  9. PON1 L55M polymorphism might contribute to the risk of cancer.

    Science.gov (United States)

    Hu, Peizeng; Ma, Yongchen; Zhang, Lingling; Ma, Sheng

    2017-03-01

    The results involved in correlation of PON1 L55M polymorphism and cancer risk are still inconsistent and controversial. Therefore, we performed this comprehensive meta-analysis for the effects of PON1 L55M polymorphism and cancer risk. We carried out a database search in PubMed (Medline) and EMBASE covering all published articles. The strength of association between PON1 L55M polymorphism and cancer risk was estimated by pooled ORs with corresponding 95% confidence intervals (CI). Twenty-one independent case-control studies concerned with association between PON1 L55M polymorphism and cancer risk were finally included in this meta-analysis. We found that there was a statistical significance between PON1 L55M polymorphism and cancer risk (OR=1.21, 95% CI: 1.04-1.40). In stratified analyses by site of cancer, statistically significant increased breast cancer risk was found (OR=2.04, 95% CI: 1.29-3.21). In stratified analyses by ethnicity, statistically significant increased cancer risk was found in Caucasian populations (OR=1.25, 95% CI: 1.03-1.51). In stratified analyses by source of control, significant increased cancer risk was found in hospital-based studies (OR=1.26, 95% CI: 1.10-1.44). This meta-analysis suggested that PON1 L55M polymorphism might increase the risk of cancer.

  10. Serum arylesterase and paraoxonase activity in patients with chronic hepatitis

    Institute of Scientific and Technical Information of China (English)

    Suleyman Sirri Kilic; Suleyman Aydin; Nermin Kilic; Fazilet Erman; Suna Aydin; (I)lhami Celik

    2005-01-01

    AIM: To investigate the relationship between serum paraoxonase (PON1), AST, ALT, GGT, and arylesterase (AE) activity alterations and the degree of liver damage in patients with chronic hepatitis.METHODS: We studied 34 chronic hepatitis patients and 32 control subjects, aged between 35 and 65 years,in the Department of Infection and Clinical Microbiology at the Firat University School of Medicine. Blood samples were collected from subjects between 8:00 and 10:00 a.m. following a 12-h fast. Baseline and salt-stimulated PON1 activities were measured by the hydrolysis of paraoxon. Phenyl acetate was used as the substrate and formed phenol was measured spectrophotometrically at 270 nm after the addition of a 10-fold diluted serum sample in AE activity measurements.RESULTS: The results of this investigation revealed that the levels of AE activity decreased from 132±52 to 94±36 (29%), baseline PON1 activity from 452±112 to 164±67 (64%), salt-stimulated PON1 activity from 746±394 to 294±220 (61%), HDL from 58.4±5.1 to 47.2±5.6(20%), triglyceride from 133±51.2 to 86±34.0 (35%),while a slight increase in the level of LDL (from 163±54.1 to 177.3±56.0; 9%) and significant increases in the levels of AST (from 29±9.3 to 98±44), ALP (from 57.2±13.1 to 91±38.1), ALT (from 27.9±3.32 to 89±19.1), GGT (from 24.3±2.10 to 94±48.2), total bilirubin (from 0.74±0.02 to 1.36±0.06; 84%) and direct bilirubin (from 0.18±0.01 to 0.42±0.04; 133%) were detected.However, the levels of albumin, total protein, cholesterol,and uric acid were almost the same in chronic hepatitis and the control subjects.CONCLUSION: Low PON1 and AE activity may contribute to the increased liver dysfunction in chronic hepatitis patients by reducing the ability of HDL to retard LDL oxidation and might be clinically useful for monitoring the disease of chronic hepatitis.

  11. Continuous reduction of plasma paraoxonase activity with increasing dialysis vintage in hemodialysis patients

    DEFF Research Database (Denmark)

    Henning, Bernhard F; Holzhausen, Helge; Tepel, Martin

    2010-01-01

    Plasma paraoxonase (PON) is an enzyme that hydrolyzes organic phosphate and aromatic carboxylic acid esters. Reduced activity is associated with early events of atherogenesis. The relevance of PON phenotypes is not well characterized in hemodialysis patients. In a cross-sectional study we measured...... phenotypes. 74% of hemodialysis patients showed PON phenotype 1, 21% PON phenotype 2, and 5% PON phenotype 3. Compared to hemodialysis patients with PON 1, patients with PON 2 or 3 showed higher conversion rates for 4-nitrophenylacetate. We observed a significant reduction of PON ratio with increasing...

  12. Paraoxonase 1: a better atherosclerotic risk predictor than HDL in type 2 diabetes mellitus.

    Science.gov (United States)

    Patra, Surajeet Kumar; Singh, Kamna; Singh, Ritu

    2013-01-01

    Type 2 diabetes mellitus is a state of glycative stress and oxidative stress. Lower level of serum PON 1 has been correlated to higher morbidity and mortality related to cardiovascular complications in type 2 diabetes mellitus. To estimate and compare the serum PON 1 levels in type 2 diabetes mellitus and controls and to predict which one is the better atherosclerotic risk predictor among HDL and PON 1 in T2DM patients. An observational analytical case-control study was conducted with a sample size of 30 in two groups like group I (30 cases of type 2 diabetes mellitus diagnosed by ADA 2010 criteria) and group II (30 age and sex matched controls). Human serum paroxonase 1 levels were measured by ELISA. Both HDL and PON 1 were negatively correlated with the various atherogenic indices (AIP, AC, CRI I, CRI II) but the strength of negative correlation is always greater for PON 1. In multiple linear regression analysis, we found that the regression coefficient (β) is always higher for PON 1 than for HDL while taking the atherogenic indices as outcome variable. PON 1 can be a better predictor than HDL for atherosclerotic risk in type 2 diabetes mellitus. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  13. Proteomic and lipidomic analyses of paraoxonase defined high density lipoprotein particles: Association of paraoxonase with the anti-coagulant, protein S.

    Science.gov (United States)

    Moren, Xenia; Lhomme, Marie; Bulla, Alexandre; Sanchez, Jean-Charles; Kontush, Anatol; James, Richard W

    2016-03-01

    Characterizing high density lipoprotein (HDL) particles and their relevance to HDL function is a major research objective. One aim is to identify functionally distinct particles. To try to limit both functional and compositional heterogeneity the present study focused on paraoxonase-1 (PON1) as a target for isolation of a minor HDL subfraction. Immunoaffinity techniques were applied to isolate PON1-containing HDL (P-HDL) and total HDL (T-HDL), which were subsequently characterized and compared. Analyses of the lipidomes showed significant differences between the fractions in the relative concentrations of individual lipid subspecies, notably reduced levels of unsaturated lysophosphatidylcholine (p < 0.05) in P-HDL (reflected in a significantly reduced total lysophosphatidylcholine polyunsaturated fatty acid content, p < 0.004). Significant differences were also observed for the proteomes. P-HDL was highly enriched in the anti-coagulant, vitamin K activated protein S (prot S) (p < 0.0001), and alpha2 macroglobulin (p < 0.01), compared to T-HDL. Conversely, procoagulant proteins kininogen 1 and histidine-rich glycoprotein were largely excluded from P-HDL. Immunoabsorption of PON1 from plasma significantly reduced prot S anti-coagulant activity. The P-HDL lipidome and proteome showed significant differences from T-HDL. Enrichment in anti-coagulation proteins indicates complementary functionalities within P-HDL particles and underlines their anti-atherosclerotic potential. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Paraoxonase 1 in Chronic Kidney Failure

    Directory of Open Access Journals (Sweden)

    Alejandro Gugliucci

    2012-01-01

    Full Text Available In this review we summarize the findings from the literature and our own laboratory on the decreased PON1 activity in renal failure, the mechanisms proposed and the effect of interventions. In addition to profound alterations in lipoproteins, reduced serum PON1 activity has been clearly established in the past decade and could contribute to accelerated development of atherosclerosis in ESRD and in HD. PON1 lactonase activity is lower in ESRD patients. Hemodialysis partially restores PON1 lactonase and the other activities. PON1 activity recovery after dialysis suggests that uremic toxins may play a mechanistic role in PON1 inactivation. Lower PON1 activity in CRF patients is associated with low thiol concentration, high CRP, and is beneficially enhanced with vitamin C and flavonoids. Changes in HDL subclasses, namely lower HDL3 in these patients may also play a role in PON1 lower activity. Future research should focus on: (1 mechanistic studies on causes for low PON1 activity and mass; (2 prospective studies focusing on whether there is an added predictive value in measuring PON1 activity (and PON1 activity in HDL3 in this patient population; (3 intervention studies attempting to increase PON1 activity.

  15. Circulating Fibroblast Growth Factor-23 Level and Paraoxonase-1 Lactonase Activity in Chronic Hemodialysis Patients: Their Impact on the Incidence of Native AV Fistula Thrombosis.

    Science.gov (United States)

    Zohny, Samir F; El-Fattah, Mahmoud Abd; Khan, Jalaluddin A

    2016-10-14

    Thrombosis of native arteriovenous (AV) fistula is an important cause of complications in hemodialysis (HD) patients. The purpose of this study was to investigate the usefulness of measuring circulating fibroblast growth factor-23 (FGF-23) level and paraoxonase-1 (PON1) lactonase activity as potential predictors of native AV fistula thrombosis in chronic HD patients. This study included 83 HD patients (48 with thrombosed and 35 with non-thrombosed native AV fistulas) and 38 healthy volunteers. Serum FGF-23 level was measured using the ELISA technique, while serum PON1 lactonase activity was measured spectrophotometrically using gamma-thiobutyrolactone as a substrate. FGF-23 was significantly increased while PON1 lactonase was markedly decreased in both thrombosed and non-thrombosed HD patients compared with controls (P AV fistulas compared with HD patients with non-thrombosed native AV fistulas (P = 0.001 and 0.002, respectively). A significant negative correlation was found between FGF-23 and PON1 lactonase in HD patients with thrombosed native AV fistulas (r = -0.342, P = 0.017). This study shows a potential value of FGF-23 and PON1 lactonase as predictors of native AV fistula thrombosis in HD patients.

  16. Assessing Protection Against OP Pesticides and Nerve Agents Provided by Wild-Type HuPON1 Purified from Trichoplusia ni Larvae or Induced via Adenoviral Infection

    Science.gov (United States)

    2013-01-01

    times the median lethal dose (LD50) of the OP nerve agents tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF), or chlorpyrifos oxon, the toxic...Doctor, M.P. Nambiar, Efficient hydrolysis of the chemical warfare nerve agent tabun by recombinant and purified human and rabbit serum paraoxonase

  17. Serum paraoxonase-1 activity is more closely related to HDL particle concentration and large HDL particles than to HDL cholesterol in Type 2 diabetic and non-diabetic subjects.

    Science.gov (United States)

    Dullaart, Robin P F; Otvos, James D; James, Richard W

    2014-08-01

    We determined relationships of the anti-oxidative enzyme, paraoxonase-1 (PON-1), with high density lipoprotein (HDL) subfractions, and tested whether these relationships are stronger than those with HDL cholesterol and apolipoprotein A-I (apoA-I) in subjects with and without type 2 diabetes mellitus (T2DM). Serum PON-1 (arylesterase activity) and HDL subfractions (nuclear magnetic resonance spectroscopy) were determined in 67 T2DM patients and in 56 non-diabetic subjects. PON-1 activity, HDL cholesterol and apoA-I were decreased in T2DM (all pHDL particle concentration was unaltered, but large HDL particles, medium HDL particles and HDL particle size were decreased, whereas small HDL particles were increased in T2DM (all pHDL cholesterol than to apoA-I (p=0.001). In turn, the positive relationship of PON-1 with the HDL particle concentration and with large HDL particles was stronger than that with HDL cholesterol (both pHDL cholesterol or HDL particle characteristics. PON-1 activity is more closely related to the HDL particle concentration or large HDL particles than to HDL cholesterol. Impaired PON-1 activity in T2DM is not to a considerable extent explained by altered HDL subfraction levels. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  18. Paraoxonase-1 activity and pleiotropic properties of simvastatin in obese and non-obese patients with stable coronary artery disease (CAD).

    Science.gov (United States)

    Januszek, Rafał

    2016-01-01

    The study was aimed to assess paraoxonase-1 (PON1) activity, pleiotropic effects of simvastatin, and its relationship to Q192R and M55L polymorphisms in obese and non-obese subjects with stable coronary artery disease (CAD). The study included 53 subjects (22 obese) aged from 35 to 65 years with CAD. The control group consisted of 53 (18 obese) police officers without CAD. Patients with CAD were treated with simvastatin 40 mg/day for 12 months. The lipid profile, flow mediated dilation (FMD), intima media-thickness (IMT), fibrinogen, hs-CRP, TNF-α, urine 8-iso-PGF2α, and PON1 activity were evaluated in definite time points. PON1 polymorphisms were assessed at baseline in all observed individuals. The patients with CAD and obesity presented at baseline significantly increased hs-CRP level, insignificantly decreased FMD and lower PON1 activity compared to non-obese individuals. There was no association of obesity with 8-iso-PGF2α in the CAD and control group. The PON1 activity was significantly higher in 192R carriers in patients and controls, irrespective of obesity. Obesity was not associated with the effects of simvastatin on PON1 activity, urine 8-iso-PGF2α, and TNF-α, whereas it blunted its effect on the FMD improvement. The Q192R polymorphism was associated with simvastatin effectiveness on hs-CRP and FMD. Obesity and Q192R PON1 polymorphism are significantly associated with pleiotropic effects of simvastatin therapy in patients with stable CAD.

  19. Interactions between paraoxonase 1 genetic polymorphisms and smoking and their effects on oxidative stress and lung cancer risk in a Korean population.

    Science.gov (United States)

    Eom, Sang-Yong; Yim, Dong-Hyuk; Lee, Chul-Ho; Choe, Kang-Hyeon; An, Jin Young; Lee, Kye Young; Kim, Yong-Dae; Kim, Heon

    2015-01-01

    Few studies in epidemiology have evaluated the effects of gene-environment interaction on oxidative stress, even though this interaction is an important etiologic factor in lung carcinogenesis. We investigated the effects of the genetic polymorphisms of paraoxonase 1 (PON1), smoking, and the interaction between the two on lung cancer risk and oxidative stress. This study's subjects consisted of 416 newly diagnosed lung cancer patients and an equal number of matched controls. The GoldenGate assay was used for genotypic analyses of the PON1 gene. Urinary 8-hydroxydeoxyguanosine (8-OHdG) and thiobarbituric acid reactive substances levels were measured as indicators of oxidative stress. The PON1 rs662 AA genotype showed a significantly lower risk of lung cancer than the GG genotype (OR = 0.60, 95% CI: 0.36-0.99). The protective effect of the PON1 rs662 AA genotype on lung cancer risk was limited to non-smokers. Lung cancer patients who had the rs662 A allele showed a dose-dependent association between smoking status and oxidative stress markers. Among non-smoking lung cancer patients, urinary 8-OHdG levels were significantly lower in individuals with the rs662 GA and AA genotypes than in those with the GG genotype. Furthermore, we found a significant interaction effect between PON1 rs662 and smoking status on urinary 8-OHdG levels in lung cancer patients. Our results suggest that the protective effect of PON1 rs662 SNP against lung carcinogenesis and the induction of oxidative stress might be modulated by the interaction between PON1 genetic polymorphisms and tobacco smoking.

  20. A variant of human paraoxonase/arylesterase (HUMPONA) gene is a risk factor for coronary artery disease.

    Science.gov (United States)

    Serrato, M; Marian, A J

    1995-12-01

    Coronary artery disease (CAD) is a complex trait caused by a number of genetic and environmental factors. Recently, paraoxonase/arylesterase (PONA) enzyme has been implicated in the pathogenesis of atherosclerosis. There is a 10-40-fold variability in the activity of this enzyme among individuals. This variability is due to the presence of an A/G polymorphism in the coding region of the gene (HUMPONA). The A and G alleles code for glutamine (A genotype) and arginine (B genotype), respectively. Individuals with A genotype have a lower enzymatic activity than those with B genotype. We determined the HUMPONA genotypes and alleles in 223 patients with angiographically documented CAD and in 247 individuals in the general population. The distribution of genotypes were in Hardy-Weinberg equilibrium in patients and in controls. Genotypes A and B were present in 120 (49%) and 28 (11%) individuals in controls and in 68 (30%) and 40 (18%) patients with CAD, respectively (chi squared= 16.5, P= 0.0003). The frequency of the A allele was 0.69 in controls and 0.56 in patients (OR= 1.7, P= 0.0001). There were no differences in the distribution of HUMPONA genotypes in the subgroups of patients with restenosis, myocardial infarction, or any of the conventional risk factors for CAD as compared with corresponding subgroups. In summary, variants of the HUMPONA gene are involved in predisposition to coronary atherosclerosis.

  1. The assessment of carotid intima media thickness and serum Paraoxonase-1 activity in Helicobacter pylori positive subjects

    Directory of Open Access Journals (Sweden)

    Akbas Halide S

    2010-08-01

    Full Text Available Abstract Background The role of inflammation in the pathogenesis and progression of atherosclerosis has been increasingly discussed. Although the seroepidemiological studies have suggested a relationship between Helicobacter pylori (H. pylori infection and atherosclerosis; the issue is still controversial. It is well known that abnormal lipid profil is related to atherosclerosis and the measurement of carotid-intima media thickness (CIMT is one of the surrogate marker of atherosclerosis. The serum concentration of high-density lipoprotein (HDL-C has been known to have an inverse correlation with the development of atherosclerosis. Paraoxonase-1 (PON1 is a major anti-atherosclerotic component of HDL-C. PON1 activity is related to lipid peroxidation and prospective cardiovascular risk. The aim of this study was to investigate CIMT and serum PON1 activities along with lipid parameters in H. pylori positive and negative subjects. Methods Thirty H. pylori positive subjects and thirty-one negative subjects were enrolled. H. pylori infection was diagnosed by the presence of positivity of stool H. pylori antigen test or Carbon 14 labeled urea breath test. Serum PON1 activity was measured spectrophotometrically. Traditional cardiovascular risk factors were investigated and laboratory analysis included measurement of serum triglycerides (TG, total cholesterol (TC, high-density lipoprotein (HDL-C and low-density lipoprotein cholesterol (LDL-C. We assessed CIMT by high-resolution ultrasound of both common carotid arteries. Results We found that the mean and maximum values of right and overall CIMT in H. pylori positive subjects were significantly thicker than those of H. pylori negative subjects. There was no significant differences in serum HDL-C, LDL-C, TC levels and TC/HDL-C ratios between two groups. Serum TG levels of H. pylori positive subjects were significantly higher than those of H. pylori negative subjects (p = 0.014. We found that PON1

  2. Paraoxonase 1 activity in subchronic low-level inorganic arsenic exposure through drinking water.

    Science.gov (United States)

    Afolabi, Olusegun K; Wusu, Adedoja D; Ogunrinola, Olufunmilayo O; Abam, Esther O; Babayemi, David O; Dosumu, Oluwatosin A; Onunkwor, Okechukwu B; Balogun, Elizabeth A; Odukoya, Olusegun O; Ademuyiwa, Oladipo

    2016-02-01

    Epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and cardiovascular diseases. While the exact mechanism of this arsenic-mediated increase in cardiovascular risk factors remains enigmatic, epidemiological studies indicate a role for paraoxonase 1 (PON1) in cardiovascular diseases. To investigate the association between inorganic arsenic exposure and cardiovascular diseases, rats were exposed to sodium arsenite (trivalent; 50, 100, and 150 ppm As) and sodium arsenate (pentavalent; 100, 150, and 200 ppm As) in their drinking water for 12 weeks. PON1 activity towards paraoxon (PONase) and phenylacetate (AREase) in plasma, lipoproteins, hepatic, and brain microsomal fractions were determined. Inhibition of PONase and AREase in plasma and HDL characterized the effects of the two arsenicals. While the trivalent arsenite inhibited PONase by 33% (plasma) and 46% (HDL), respectively, the pentavalent arsenate inhibited the enzyme by 41 and 34%, respectively. AREase activity was inhibited by 52 and 48% by arsenite, whereas the inhibition amounted to 72 and 67%, respectively by arsenate. The pattern of inhibition in plasma and HDL indicates that arsenite induced a dose-dependent inhibition of PONase whereas arsenate induced a dose-dependent inhibition of AREase. In the VLDL + LDL, arsenate inhibited PONase and AREase while arsenite inhibited PONase. In the hepatic and brain microsomal fractions, only the PONase enzyme was inhibited by the two arsenicals. The inhibition was more pronounced in the hepatic microsomes where a 70% inhibition was observed at the highest dose of pentavalent arsenic. Microsomal cholesterol was increased by the two arsenicals resulting in increased cholesterol/phospholipid ratios. Our findings indicate that decreased PON1 activity observed in arsenic exposure may be an incipient biochemical event in the cardiovascular effects of arsenic. Modulation of PON1 activity by arsenic may also be

  3. CORRELATION BETWEEN SERUM PARAOXONASE ACTIVITY AND HIGH DENSITY LIPOPROTEIN LEVELS IN TYPE2 DIABETES PREDISPOSING TO ATEROSCLEROSIS

    Directory of Open Access Journals (Sweden)

    SK.Deepthi

    2014-11-01

    Full Text Available Human serum paraoxonase is physically associated with HDL and has been implicated in the detoxification of organophosphates and possibly in the prevention of LDL lipid peroxidation and therefore retards atherosclerosis. HDL levels are inversely related to the risk of developing atherosclerosis. We investigated the serum activity and concentration of paraoxonase and HDL levels in 104 subjects (42 diabetic patients without complications, 42 controls, 20 diabetic patients with complications.. Paraoxonase activity was found to be lower in diabetic patients than in controls. Similarly there was reduction in HDL levels in cases suggesting a positive correlation between HDL and paraoxonase levels.

  4. Individuals with autism have higher 8-Iso-PGF2α levels than controls, but no correlation with quantitative assay of Paraoxonase 1 serum levels.

    Science.gov (United States)

    Pop, Bianca; Niculae, Alexandru-Ștefan; Pop, Tudor Lucian; Răchișan, Andreea Liana

    2017-08-14

    Autism spectrum disorder (ASD) represents a very large set of neurodevelopmental issues with diverse clinical outcomes. Various hypotheses have been put forth for the etiology of autism spectrum disorder, including issues pertaining to oxidative stress. In this study, we conducted measurements of serum 8-Iso-Prostaglanding F2 α (8-iso-PGF2α, which is the results of non-enzimatically mediated polyunsaturated fatty acid oxidation) in a population of individuals with autism and a control group of age and sex matched controls. A quantitative assay of Paraoxonase 1 (PON1) was conducted. Data regarding comorbidities, structural MRI scans, medication, intelligence quotient (IQ) and Childhood Autism Rating Scale scores (CARS) were also included in our study. Our results show that patients diagnosed with autism have higher levels of 8-iso-PGF2α than their neurotypical counterparts. Levels of this particular metabolite, however, do not correlate with quantitative serum levels of Paraoxonase 1, which has been shown to be altered in individuals with autism. Neither 8-iso-PGF2α nor quantitative levels of PON1 provide any meaningful correlation with clinical or neuroimaging data in this study group. Future research should focus on providing data regarding PON 1 phenotype, in addition to standard quantitative measurements, in relation to 8-iso-PGF2α as well as other clinical and structural brain findings.

  5. Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions.

    Science.gov (United States)

    D'Amelio, M; Ricci, I; Sacco, R; Liu, X; D'Agruma, L; Muscarella, L A; Guarnieri, V; Militerni, R; Bravaccio, C; Elia, M; Schneider, C; Melmed, R; Trillo, S; Pascucci, T; Puglisi-Allegra, S; Reichelt, K-L; Macciardi, F; Holden, J J A; Persico, A M

    2005-11-01

    Organophosphates (OPs) are routinely used as pesticides in agriculture and as insecticides within the household. Our prior work on Reelin and APOE delineated a gene-environment interactive model of autism pathogenesis, whereby genetically vulnerable individuals prenatally exposed to OPs during critical periods in neurodevelopment could undergo altered neuronal migration, resulting in an autistic syndrome. Since household use of OPs is far greater in the USA than in Italy, this model was predicted to hold validity in North America, but not in Europe. Here, we indirectly test this hypothesis by assessing linkage/association between autism and variants of the paraoxonase gene (PON1) encoding paraoxonase, the enzyme responsible for OP detoxification. Three functional single nucleotide polymorphisms, PON1 C-108T, L55M, and Q192R, were assessed in 177 Italian and 107 Caucasian-American complete trios with primary autistic probands. As predicted, Caucasian-American and not Italian families display a significant association between autism and PON1 variants less active in vitro on the OP diazinon (R192), according to case-control contrasts (Q192R: chi2=6.33, 1 df, Pautism pathogenesis in a sizable subgroup of North American individuals.

  6. Correlation between PON1 gene polymorphisms and breast cancer risk: a Meta-analysis.

    Science.gov (United States)

    Wen, Yayuan; Huang, Zemin; Zhang, Xiaohua; Gao, Bo; He, Yujun

    2015-01-01

    A number of studies have investigated the relationship between the PON1 gene polymorphisms and breast cancer risk, but the conclusions are not consistent. In this paper, a meta-analysis was conducted to explore the possible reasons for these inconsistencies, expecting to further clarify the correlation between PON1 gene polymorphisms and breast cancer risk. After searches in the database such as MEDLINE, EBSCO, ProQuest, Google Scholar, High-Wire, SID (Scientific Information Database) and PubMed, 7 literatures were collected. RevMan 5.2 software was used to perform the meta-analysis. Random-effects or fixed-effects model was used to analyze the odds ratio (OR) and 95% confidence intervals. The analysis of L55M single nucleotide polymorphisms (SNPs) showed that M allele frequency was positively correlated with the incidence risk of breast cancer (OR=1.34, 95% CI: 1.03-1.74). While we did not found Q192R polymorphism associated with the risk of breast cancer (OR=1.0, 95% CI: 0.71-1.42). For PON1 gene, the frequencies of M allele were associated with the incidence risk of breast cancer.

  7. [The different genotypes of MTHFR 1298A>C and PON1 -108C>T polymorphisms confer the increased risk of the abdominal aortic aneurysm in the smoking and nonsmoking persons].

    Science.gov (United States)

    Strauss, Ewa; Waliszewski, Krzysztof; Pawlak, Andrzej L

    2005-01-01

    In abdominal aortic aneurysm (AAA) both the etiology and the pathogenesis are of the multifactorial character. The genetic component in the determination of this disease is proven by its familial occurrence. Smoking represents the best recognized risk factor of the AAA development. Increased concentrations of homocysteine (Hcy) in plasma are the common finding in these patients. It is assumed that the Hcy thiolactone, the most reactive metabolite of Hcy, may participate in the aortic wall destruction in AAA. The polymorphic variants of the methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C) influence tissue concentrations of the Hcy. Paraoxonase (PON1), the enzyme associated in plasma with the HDL fraction, as lactonase detoxicates the Hcy thiolactone. The promotor polymorphism of PON1 - 108C>T gene may determine the lower activity of this enzyme. In the case-control study of 106 patients with AAA and 97 healthy persons, the effects of selected genetic and nongenetic risk factors on development of AAA were assessed, considering the possibilities of interaction between them. It was found, that the arterial hypertension, cigarette smoking and the lower HDL fraction are independent risk factors of AAA. The arterial hypertension was a risk factor both in the smoking and the nonsmoking males, whereas the lower HDL fraction has been the risk factor only for the smoking men. By the multivariate analysis in the nonsmoking males the MTHFR 1298 AC and CC genotypes increased the risk of AAA development 4,8-fold in relation to the MTHFR 1298 AA nonsmoking males. In reference to the genotypes of the expected high impact on the metabolism of Hcy and of Hcy thiolactone, the genotypes of MTHFR 677TT and PON1 -108CT and TT were more frequent in smoking ones, but the difference was not significant. This observation fits with the assumption that the influence of smoking on the occurrence of AAA prevails over that of genetic variability. When the patients age was considered

  8. Influence of paraoxonase-1 Q192R and cytochrome P450 2C19 polymorphisms on clopidogrel response

    Directory of Open Access Journals (Sweden)

    Li L

    2012-02-01

    Full Text Available Rolf P Kreutz1,2, Perry Nystrom2, Yvonne Kreutz2, Jia Miao2, Zeruesenay Desta2, Jeffrey A Breall1, Lang Li2, ChienWei Chiang2, Richard Kovacs1, David A Flockhart2, Yan Jin21Krannert Institute of Cardiology, 2Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USABackground: The metabolic activation of clopidogrel is a two-step process. It has been suggested that paraoxonase-1 (PON1 is a rate-limiting enzyme in the conversion of 2-oxo-clopidogrel to an active thiol metabolite. Conflicting results have been reported in regard to (1 the association of a common polymorphism of PON1 (Q192R with reduced rates of coronary stent thrombosis in patients taking clopidogrel and (2 its effects on platelet inhibition in patient populations of European descent. Methods: Blood samples from 151 subjects of mixed racial background with established coronary artery disease and who received clopidogrel were analyzed. Platelet aggregation was determined with light transmittance aggregometry and VerifyNow® P2Y12 assay. Genotyping for cytochrome P450 2C19 (CYP2C19*2 and *3 and PON1 (Q192R polymorphisms was performed.Results: Carriers of CYP2C19*2 alleles exhibited lower levels of platelet inhibition and higher on-treatment platelet aggregation than noncarriers. There was no significant difference in platelet aggregation among PON1 Q192R genotypes. Homozygous carriers of the wild-type variant of PON1 (QQ192 had similar on-treatment platelet reactivity to carriers of increased-function variant alleles during maintenance clopidogrel dosing, as well as after administration of a clopidogrel 600 mg loading dose.Conclusion: CYP2C19*2 allele is associated with impaired platelet inhibition by clopidogrel and high on-treatment platelet aggregation. PON1 (Q192R polymorphism does not appear to be a significant determinant of clopidogrel response.Keywords: PON1, platelet, aggregation, cytochrome P450 enzymes

  9. Açai (Euterpe oleracea Mart.) Upregulates Paraoxonase 1 Gene Expression and Activity with Concomitant Reduction of Hepatic Steatosis in High-Fat Diet-Fed Rats

    Science.gov (United States)

    Lage, Nara Nunes; Lopes, Juliana Márcia Macedo; de Lima, Wanderson Geraldo

    2016-01-01

    Açai (Euterpe oleracea Mart.), a fruit from the Amazon region, has emerged as a promising source of polyphenols. Açai consumption has been increasing owing to ascribed health benefits and antioxidant properties; however, its effects on hepatic injury are limited. In this study, we evaluated the antioxidant effect of filtered açai pulp on the expression of paraoxonase (PON) isoforms and PON1 activity in rats with nonalcoholic fatty liver disease (NAFLD). The rats were fed a standard AIN-93M (control) diet or a high-fat (HF) diet containing 25% soy oil and 1% cholesterol with or without açai pulp (2 g/day) for 6 weeks. Our results show that açai pulp prevented low-density lipoprotein (LDL) oxidation, increased serum and hepatic PON1 activity, and upregulated the expression of PON1 and ApoA-I in the liver. In HF diet-fed rats, treatment with açai pulp attenuated liver damage, reducing fat infiltration and triglyceride (TG) content. In rats receiving açai, increased serum PON1 activity was correlated with a reduction in hepatic steatosis and hepatic injury. These findings suggest the use of açai as a potential therapy for liver injuries, supporting the idea that dietary antioxidants are a promising approach to enhance the defensive systems against oxidative stress. PMID:27642496

  10. Açai (Euterpe oleracea Mart. Upregulates Paraoxonase 1 Gene Expression and Activity with Concomitant Reduction of Hepatic Steatosis in High-Fat Diet-Fed Rats

    Directory of Open Access Journals (Sweden)

    Renata Rebeca Pereira

    2016-01-01

    Full Text Available Açai (Euterpe oleracea Mart., a fruit from the Amazon region, has emerged as a promising source of polyphenols. Açai consumption has been increasing owing to ascribed health benefits and antioxidant properties; however, its effects on hepatic injury are limited. In this study, we evaluated the antioxidant effect of filtered açai pulp on the expression of paraoxonase (PON isoforms and PON1 activity in rats with nonalcoholic fatty liver disease (NAFLD. The rats were fed a standard AIN-93M (control diet or a high-fat (HF diet containing 25% soy oil and 1% cholesterol with or without açai pulp (2 g/day for 6 weeks. Our results show that açai pulp prevented low-density lipoprotein (LDL oxidation, increased serum and hepatic PON1 activity, and upregulated the expression of PON1 and ApoA-I in the liver. In HF diet-fed rats, treatment with açai pulp attenuated liver damage, reducing fat infiltration and triglyceride (TG content. In rats receiving açai, increased serum PON1 activity was correlated with a reduction in hepatic steatosis and hepatic injury. These findings suggest the use of açai as a potential therapy for liver injuries, supporting the idea that dietary antioxidants are a promising approach to enhance the defensive systems against oxidative stress.

  11. Catalytic stimulation by restrained active-site floppiness--the case of high density lipoprotein-bound serum paraoxonase-1.

    Science.gov (United States)

    Ben-David, Moshe; Sussman, Joel L; Maxwell, Christopher I; Szeler, Klaudia; Kamerlin, Shina C L; Tawfik, Dan S

    2015-03-27

    Despite the abundance of membrane-associated enzymes, the mechanism by which membrane binding stabilizes these enzymes and stimulates their catalysis remains largely unknown. Serum paraoxonase-1 (PON1) is a lipophilic lactonase whose stability and enzymatic activity are dramatically stimulated when associated with high-density lipoprotein (HDL) particles. Our mutational and structural analyses, combined with empirical valence bond simulations, reveal a network of hydrogen bonds that connect HDL binding residues with Asn168--a key catalytic residue residing >15Å from the HDL contacting interface. This network ensures precise alignment of N168, which, in turn, ligates PON1's catalytic calcium and aligns the lactone substrate for catalysis. HDL binding restrains the overall motion of the active site and particularly of N168, thus reducing the catalytic activation energy barrier. We demonstrate herein that disturbance of this network, even at its most far-reaching periphery, undermines PON1's activity. Membrane binding thus immobilizes long-range interactions via second- and third-shell residues that reduce the active site's floppiness and pre-organize the catalytic residues. Although this network is critical for efficient catalysis, as demonstrated here, unraveling these long-rage interaction networks is challenging, let alone their implementation in artificial enzyme design.

  12. Analysis of Coexisting GPON and NG-PON1 (10G-PON Systems

    Directory of Open Access Journals (Sweden)

    M. D. Mraković

    2011-06-01

    Full Text Available In this paper, the simulation model of coexisting GPON and NG-PON1 (10G-PON systems is presented, which has been developed for the analysis of feasibility and implementation issues of this coexistence. The aim was to analyze the impact of the most important parameters of the components that are needed for new network elements, on the performance of these coexistent networks. On the basis of the results obtained, the optimal parameters of the new system components were defined.

  13. Continuous reduction of plasma paraoxonase activity with increasing dialysis vintage in hemodialysis patients.

    Science.gov (United States)

    Henning, Bernhard F; Holzhausen, Helge; Tepel, Martin

    2010-12-01

    Plasma paraoxonase (PON) is an enzyme that hydrolyzes organic phosphate and aromatic carboxylic acid esters. Reduced activity is associated with early events of atherogenesis. The relevance of PON phenotypes is not well characterized in hemodialysis patients. In a cross-sectional study we measured PON activity in 377 hemodialysis patients photometrically using the substrates 4-nitrophenylacetate and phenylacetate. The PON ratio was calculated from 4-nitrophenylacetate-derived activity divided by phenylacetate-derived activity. Frequency distribution of the PON ratio showed three different PON phenotypes. 74% of hemodialysis patients showed PON phenotype 1, 21% PON phenotype 2, and 5% PON phenotype 3. Compared to hemodialysis patients with PON 1, patients with PON 2 or 3 showed higher conversion rates for 4-nitrophenylacetate. We observed a significant reduction of PON ratio with increasing dialysis vintage (Pvintage. In conclusion, plasma PON ratio significantly declines with increasing dialysis vintage.

  14. Lack of an association between Paraoxonase 1 gene polymorphisms (Q192R, L55M) and Alzheimer's disease: a meta-analysis.

    Science.gov (United States)

    Pi, Yan; Zhang, Lili; Chang, Kai; Li, Binghu; Guo, Lu; Fang, Chuanqin; Gao, Changyue; Wang, Jingzhou; Xiang, Jing; Li, Jingcheng

    2012-08-15

    The association between Paraoxonase 1 (PON1) gene polymorphisms (Q192R, L55M) and Alzheimer's disease (AD) risk has been reported inconsistent results. To assess the association between PON1 polymorphisms and AD risk, a meta-analysis was performed. Based on comprehensive searches of the PubMed, Embase, Web of Science, Weipu, and CBM databases, a total of 10 studies including 3081 AD cases and 3054 controls were identified. The pooled odds ratio (OR) with 95% confidence interval (95% CI) were performed. There was no significant association between PON1 Q192R polymorphism and AD risk in all comparison models (R vs. Q, OR=0.89, 95% CI=0.82-0.96; RR vs. QQ, OR=0.83, 95% CI=0.68-1.01; RR+RQ vs. QQ, OR=0.86, 95% CI=0.75-0.97; and RR vs. QR+QQ, OR=0.94, 95% CI=0.81-1.11). For the PON1 L55M polymorphism, lack of an association was also found (L vs. M, OR=0.95, 95% CI=0.86-1.05; LL vs. MM, OR=0.67, 95% CI=0.51-0.88; LL vs. ML+MM, OR=0.82, 95% CI=0.69-0.98; and LL+ML vs. MM, OR=0.75, 95% CI=0.58-0.96). On subgroup analysis by ethnicity, similar results were found. Conclusively, the present meta-analysis revealed that PON1 gene polymorphisms (Q192R, L55M) were unlikely to contribute to AD susceptibility. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Esterase detoxification of acetylcholinesterase inhibitors using human liver samples in vitro

    Science.gov (United States)

    Organophosphate (OP) and N-methylcarbamate pesticides inhibit acetylcholinesterase (AChE), but differences in metabolism and detoxification can influence potency of these pesticides across and within species. Carboxylesterase (CaE) and A-esterase (paraoxonase, PON1) are consider...

  16. Common variants APOC3, APOA5, APOE and PON1 are associated with variation in plasma lipoprotein traits in Greenlanders

    DEFF Research Database (Denmark)

    Lahiry, Piya; Ban, Matthew R; Pollex, Rebecca L

    2007-01-01

    OBJECTIVES: We undertook studies of the association between common genomic variations in APOC3, APOA5, APOE and PON1 genes and variation in biochemical phenotypes in a sample of Greenlanders. STUDY DESIGN: Genetic association study of quantitative lipoprotein traits. METHODS: In a sample of 1,310...

  17. Effect of Vitamin E and Selenium Supplement on Paraoxonase-1 Activity, Oxidized Low Density Lipoprotein and Antioxidant Defense in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Mohammad-Reza Rashidi

    2011-08-01

    Full Text Available Introduction: The aim of the present study was to assess the effects of vitamin E and selenium supplementation on serum paraoxonase (PON1 activity, lipid peroxidation and antioxidant defense in streptozotocin-induced diabetic rats. Methods: Thirty two female Sprague Dawley rats were divided into 3 groups: the control group (n=8 received a standard diet; streptozotocin (STZ-induced diabetic rats (n=12, received corn oil and physiological solution; and vitamin E and selenium supplemented diabetic rats (n=12 were treated with oral administration of vitamin E (300 mg/kg and sodium selenite (0.5 mg/kg once a day for 4 weeks. Results: Significantly lower total antioxidant status (TAS, PON1and erythrocyte SOD activities and a higher fasting plasma glucose level were observed in the diabetic rats compared to the control. A significant increase in SOD and GPX activities in vitamin E and selenium supplemented diabetic group was observed after 5 weeks of the experiment. Compared to the normal rats, malondialdehyde (MDA and oxidized LDL (Ox-LDL levels were higher in the diabetic animals; however, these values reduced significantly following vitamin E and selenium supplementation. Conclusion: Vitamin E and selenium supplementation in diabetic rats has hypolipidemic, hypoglycemic and antioxidative effects and may slow down the progression of diabetic complications through its protective effect on PON1 activity and lipoproteins oxidation.

  18. Benefits of Omega-3 Fatty Acids Supplementation on Serum Paraoxonase 1 Activity and Lipids Ratios in Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Elahe Mohammadi

    2012-12-01

    Full Text Available Background: Polycystic ovary syndrome (PCOS is a common endocrine disorder associated with increased risk of cardiovascular disease. The purpose of this study was to investigate the ef-fects of omega-3 fatty acids on serum paraoxonase 1 activity and lipids ratios in polycystic ovary syndrome.Methods: This double-blind randomized controlled clinical trial was conducted on 64 PCOS pa-tients with 20-35 years old. Thirty two of the subjects had taken 4 g/day omega -3 fatty acids and 32 patients were given placebo for 8 weeks. Fasting blood samples, anthropometric measure-ments and dietary intakes were collected at the beginning and the end of the study. Serum total cholesterol, triglyceride, and HDL-C were measured using the enzymatic methods. LDL-C con-centration was calculated by the Friedewald formula and arylesterase activity of serum PON1 was measured. Data were analyzed using SPSS software.Results: Omega-3 fatty acids significantly decreased TC/HDL-C and LDL-C/HDL-C ratios (P = 0.009 for both and significantly increased serum PON1 activity (P = 0.048 compared with placebo. Changes in TG/HDL-C ratio were not statistically significant in omega-3 fatty acids group at the end of the study in comparison to placebo group. Reduction in TC/HDL-C, LDL-C/HDL-C and TG/HDL-C ratios and increase in serum PON1 activity were also significant in omega-3 fatty acids group at the end of the study compared with baseline values (P <0.001, P < 0.001, P = 0.004, and P = 0.001, respectively.Conclusion: Omega-3 fatty acids may decrease the risk for cardiovascular disease through the improvement in paraxonase-1 activity and reduction in some lipids ratio in PCOS women.

  19. Paraoxonase 1 gene polymorphism does not affect clopidogrel response variability but is associated with clinical outcome after PCI.

    Directory of Open Access Journals (Sweden)

    Kyung Woo Park

    Full Text Available BACKGROUND: Paraoxonase (PON is a high-density-lipoprotein (HDL associated enzyme with antioxidative and anti-atherogenic property. Its function is associated with coronary artery disease and its activity genetically controlled. We evaluated whether genetic variation of PON-1 is associated with clinical outcome in a large cohort of Korean patients with drug-eluting stents implantation. METHODS: A total of 1676 patients with drug-eluting stent implantation were enrolled in the prospective CROSS-VERIFY cohort from June 2006 to June 2010. We genotyped the PON1-Q192R gene, measured clopidogrel on-treatment platelet reactivity (OPR, and analyzed lipid profiles. The primary endpoint was the composite of cardiac death, myocardial infarction, and stent thrombosis at 12 months. RESULTS: PON-1 genotyping data were available in 1336 patients. Since the Q-allele is associated with decreased PON-activity, we analyzed the outcome between patients with QQ/QR (815 patients, 61% and those with RR-genotype (521 patients, 39%. After adjustment for common cardiac risk factors, the QQ/QR-genotype was an independent predictor of the primary thrombotic endpoint with an 11-fold increased risk (HR 11.6, 95% CI: 1.55-87.0, but not repeat revascularization (HR 1.12, 95% CI: 0.78-1.61. The QQ/QR-genotype was not associated with OPR (QQ/QR: 231±86 PRU vs. RR 236±82 PRU, p = 0.342 but higher small-dense LDL levels (1.20±0.12 mg/dL vs. 0.76±0.15 mg/dL, p = 0.027. The increased risk of thrombotic outcomes was more profound in acute coronary syndrome (ACS patients compared with non-ACS patients. CONCLUSION: PON1 Q-allele is an independent predictor of worse cardiovascular outcome independent of platelet function and is associated with significantly higher levels of small dense LDL-C.

  20. Correlation between paraoxonase1 Leu55Met gene polymorphism and chronic periodontitis with diabetes mellitus%对氧磷酶1 Leu55Met基因多态性与牙周炎伴糖尿病的相关性研究

    Institute of Scientific and Technical Information of China (English)

    李永凯; 李丛华; 杨霞; 叶国; 侯海娟

    2014-01-01

    目的:研究对氧磷酶(paraoxonase,PON)1 Leu55Met的基因多态性与单纯牙周炎及牙周炎伴糖尿病(diabetes mellitus,DM)(本文特指2型糖尿病)的易感性是否相关.方法:收集慢性牙周炎(chronic periodontitis,CP)伴DM患者、单纯CP患者、单纯DM患者及正常人各50例口腔颊黏膜拭子,采用口腔/咽拭子基因组DNA提取试剂盒提取DNA,然后应用聚合酶链式反应-限制性片段长度多态性检测PON1 Leu55Met的基因型分布.结果:DM伴CP组(CP+DM)、单纯CP组(CP)、单纯DM患组(DM)、正常组(H)在PON1 Leu55Met基因型分布有统计学差异(x2=12.444,P=O.O06).结论:CP与DM的易感性可能与PON1 Leu55Met基因多态性有关.

  1. Effects of Iron Supplementation With and Without Docosahexaenoic Acid on the Cardiovascular Disease Risk Based on Paraoxonase-1, hs-CRP, and ApoB/ApoA-I Ratio in Women with Iron Deficiency Anemia.

    Science.gov (United States)

    Shidfar, Farzad; Amani, Samira; Vafa, Mohammadreza; Shekarriz, Ramin; Hosseini, Sharieh; Shidfar, Shahrzad; Eshraghian, Mohammadreza; Mousavi, Seyedeh Neda

    2016-01-01

    Numerous studies have demonstrated that tissue deposition of iron following prolonged high dose of oral supplementation for treatment of iron deficiency anemia (IDA) leads to body iron overload and oxidative stress, which starts the process of atherosclerosis. This study aimed to determine the effect of iron supplementation in combination with docosahexaenoic acid (DHA) on the cardiovascular disease risk based on paraoxonase-1 (PON-1), high-sensitivity C-reactive protein (hs-CRP), and ApoB/ApoA-I ratio in women with IDA. In this randomized controlled trial, 76 women with IDA, aged 15-45 years, were included. The patients were randomly assigned to receive 500 mg of DHA supplement or placebo with an iron tablet, once daily for 12 weeks. The participants were assessed by measurement of the serum iron, ferritin, PON-1, hs-CRP levels, and the ApoB/ApoA-I ratio at the beginning and end of study. Serum hs-CRP decreased in the DHA-supplemented group (p = 0.036), and ApoA-I decreased in the placebo group (p = 0.013). No significant difference was detected for the serum PON-1 concentration and the ApoB/ApoA-I ratio in two groups. Iron supplementation combined with DHA may have favorable effects on serum hs-CRP in women with IDA.

  2. Paraoxonase and arylesterase activities in adults with vitamin B12 deficiency.

    Science.gov (United States)

    Guney, Tekin; Alisik, Murat; Alkan, Afra; Basturk, Abdulkadir; Akinci, Sema; Hacibekiroglu, Tuba; Dilek, Imdat; Erel, Ozcan

    2015-09-12

    Objective The purpose of this study was to investigate paraoxonase (PON) and arylesterase (ARES) enzyme activity in adults with vitamin B12 deficiency, and specific changes in the activities of these enzymes following vitamin B12 treatment. Methods A total of 46 patients with vitamin B12 deficiency (aged 18-82 years) and 45 healthy volunteer controls (aged 19-64 years) participated in this study. Venous blood samples were collected, and serum vitamin B12, homocysteine (HCY), methylmalonic acid, PON1, and ARES levels were measured. Results Paired comparison showed that pre- and post-treatment values for PON and ARES were similar between patients and controls (both P > 0.05). There was no statistically significant relationship between patients' pre-/post-treatment PON or HCY levels and serum vitamin B12 levels, compared with those of the control group (P > 0.05). Discussion The results of the present study do not support the hypothesis that the antioxidant enzymes PON and ARES have an underlying role in vitamin B12 deficiency and related hyperhomocysteinemia. Our findings suggest that PON and ARES do not play a role in the systemic effects of vitamin B12 deficiency.

  3. A Genetic Biomarker of Oxidative Stress, the Paraoxonase-1 Q192R Gene Variant, Associates with Cardiomyopathy in CKD: A Longitudinal Study

    Directory of Open Access Journals (Sweden)

    E. Dounousi

    2016-01-01

    Full Text Available Background. Oxidative stress is a hallmark of CKD and this alteration is strongly implicated in LV hypertrophy and in LV dysfunction. Methods and Patients. We resorted to the strongest genetic biomarker of paraoxonase-1 (PON1 activity, the Q192R variant in the PON1 gene, to unbiasedly assess (Mendelian randomization the cross-sectional and longitudinal association of this gene-variant with LV mass and function in 206 CKD patients with a 3-year follow-up. Results. The R allele of Q192R polymorphism associated with oxidative stress as assessed by plasma 8-isoPGF2α (P=0.03 and was dose-dependently related in a direct fashion to LVMI (QQ: 131.4 ± 42.6 g/m2; RQ: 147.7 ± 51.1 g/m2; RR: 167.3 ± 41.9 g/m2; P=0.001 and in an inverse fashion to systolic function (LV Ejection Fraction (QQ: 79 ± 12%; RQ: 69 ± 9%; RR: 65 ± 10% P=0.002. On longitudinal observation, this gene variant associated with the evolution of the same echocardiographic indicators [LVMI: 13.40 g/m2 per risk allele, P=0.005; LVEF: −2.96% per risk allele, P=0.001]. Multivariate analyses did not modify these associations. Conclusion. In CKD patients, the R allele of the Q192R variant in the PON1 gene is dose-dependently related to the severity of LVH and LV dysfunction and associates with the longitudinal evolution of these cardiac alterations. These results are compatible with the hypothesis that oxidative stress is implicated in cardiomyopathy in CKD patients.

  4. Consumption of argan oil may have an antiatherogenic effect by improving paraoxonase activities and antioxidant status: Intervention study in healthy men.

    Science.gov (United States)

    Cherki, Mounia; Derouiche, Abdelfettah; Drissi, Anas; El Messal, Mariame; Bamou, Youssef; Idrissi-Ouadghiri, Azzedine; Khalil, Abdelouahed; Adlouni, Ahmed

    2005-10-01

    Due to its high antioxidant and mono- and polyunsaturated fatty acid content virgin argan oil (VAO) could play a beneficial role in cardiovascular prevention. We were therefore interested in determining whether the consumption of VAO could improve plasma paraoxonase (PON1) activities and antioxidant status in healthy men. Sixty young men were included in this interventional study. They were given a controlled diet for 2 weeks as baseline and then received 25 g/day of butter. The group was randomised to two diet group periods of 3 weeks each. The VAO group received 25 ml/day of oil and the extra virgin olive oil (EVO) group received the same quantity of EVO as control group. Plasma PON1 activities, antioxidant vitamins and LDL susceptibility to oxidation were measured. The analysis of the results shows that PON1 activities increase significantly in both groups and that lipoperoxides and conjugated dienes formation decreases significantly in VAO and EVO groups compared to baseline values (P=0.001 and P=0.014, respectively). Vitamin E concentration increases significantly only in VAO group (P=0.007). Susceptibility of LDL to lipid peroxidation shows a significant increase in lag phase and a significant decrease in maximum diene production in VAO (P=0.005) and EVO groups (P=0.041 and P=0.005, respectively). Our findings confirm the beneficial effect of EVO on plasma antioxidant status and show for the first time the same effect for VAO supplementation in man. Thus, VAO offers an additional natural food supplement to reduce cardiovascular risk.

  5. Lipid, Oxidative and Inflammatory Profile and Alterations in the Enzymes Paraoxonase and Butyrylcholinesterase in Plasma of Patients with Homocystinuria Due CBS Deficiency: The Vitamin B12 and Folic Acid Importance.

    Science.gov (United States)

    Vanzin, Camila Simioni; Mescka, Caroline Paula; Donida, Bruna; Hammerschimidt, Tatiane Grazieli; Ribas, Graziela S; Kolling, Janaína; Scherer, Emilene B; Vilarinho, Laura; Nogueira, Célia; Coitinho, Adriana Simon; Wajner, Moacir; Wyse, Angela T S; Vargas, Carmen Regla

    2015-08-01

    Cystathionine-β-synthase (CBS) deficiency is the main cause of homocystinuria. Homocysteine (Hcy), methionine, and other metabolites of Hcy accumulate in the body of affected patients. Despite the fact that thromboembolism represents the major cause of morbidity in CBS-deficient patients, the mechanisms of cardiovascular alterations found in homocystinuria remain unclear. In this work, we evaluated the lipid and inflammatory profile, oxidative protein damage, and the activities of the enzymes paraoxonase (PON1) and butyrylcholinesterase (BuChE) in plasma of CBS-deficient patients at diagnosis and during the treatment (protein-restricted diet supplemented with pyridoxine, folic acid, betaine, and vitamin B12). We also investigated the effect of folic acid and vitamin B12 on these parameters. We found a significant decrease in HDL cholesterol and apolipoprotein A1 (ApoA-1) levels, as well as in PON1 activity in both untreated and treated CBS-deficient patients when compared to controls. BuChE activity and IL-6 levels were significantly increased in not treated patients. Furthermore, significant positive correlations between PON1 activity and sulphydryl groups and between IL-6 levels and carbonyl content were verified. Moreover, vitamin B12 was positively correlated with PON1 and ApoA-1 levels, while folic acid was inversely correlated with total Hcy concentration, demonstrating the importance of this treatment. Our results also demonstrated that CBS-deficient patients presented important alterations in biochemical parameters, possibly caused by the metabolites of Hcy, as well as by oxidative stress, and that the adequate adherence to the treatment is essential to revert or prevent these alterations.

  6. Relationship between MPV and paraoxonase-1 activity, brachial ...

    African Journals Online (AJOL)

    activity and PON-1 activity, BAd and BA-IMT regardless of obesity and diabetic complications. Keywords: .... patients, anthropometric measurements (height, weight, body ... was considered the thickest, and where the clearest B mode image.

  7. Maintenance of Paraoxonase 2 Activity as a Strategy to Attenuate P. Aeruginosa Virulence

    Science.gov (United States)

    2015-12-01

    SUPPLEMENTARY NOTES 14. ABSTRACT The P. aeruginosa signaling/virulence molecule 3OC12 mediates inactivation of the lactonase paraoxonase 2 (PON2) and induces... mediated inactivation at 3OC12 concentrations expected to be present near P. aeruginosa colonies during infection. In mouse primary cell types PON2 was not...as sensitive to 3OC12- mediated inactivation as in human cells. We also discovered that 3OC12 is rapidly hydrolyzed intracellularly by PON2 to 3OC12

  8. Engineering of Paraoxonases for Pre- and Post-treatment of Intoxication by a Broad Spectrum of Nerve Agents and Pesticides

    Science.gov (United States)

    2014-08-01

    inhalation and skin absorption. Commercial OP pesticides such as parathion, chlopyrifos, phorate, and malathion, are also considered as threat...human paraoxonase gene cluster as a target in the treatment of atherosclerosis. Antioxidants & redox signaling 16: 597-632 van den Berg B, Tessari M

  9. Analysis of Single Nucleotide Polymorphism in Human Paraoxonase 1 Gene(Q192R) with Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Introduction Single nucleotide polymorphisms (SNPs) are the most abundant DNA markers in the human genome occurring at a frequency of one in every 500-1000 nucleotides[1]. A variety of methods have been used for the analysis of single nucleotide polymorphisms, including restriction fragment length polymorphism (RFLP) [2], direct sequencing by using laser-induced fluorescence detection[3], fluorescence energy transfer[4], MALDI-TOF MS combined with primer extension or invasive cleavage[5,6] , and fluorescence polarization[7].

  10. Purification, characterization, and investigation of in vitro inhibition by metals of paraoxonase from different sheep breeds.

    Science.gov (United States)

    Erol, Kadir; Gençer, Nahit; Arslan, Mikail; Arslan, Oktay

    2013-04-01

    Paraoxonase (PON) was purified and characterized from the Merino and Kivircik sheep's blood serums by a two-step procedure using ammonium sulphate precipitation and Sepharose-4B-L-tyrosine-1-napthylamine hydrophobic interaction chromatography for the first time. On SDS-polyacyrilamide gel electrophoresis, purified human serum paraoxonase yielded a single band of 66 kDa on SDS-PAGE. The KM and Vmax were 0.482 mM and 41.348 U/mL.dak for Merino PON enzyme, 0.153 mM and 70.289 U/mL.dak for Kivircik PON, respectively. The effect of Mn(2+) , Hg(2+) , Co(2+) , Cd(2+) , Ni(2+) and Cu(2+) heavy metals on purified Merino and Kivircik serum PON in vitro was determined.

  11. Paraoxonase 2 (PON2) in the mouse central nervous system: A neuroprotective role?

    Energy Technology Data Exchange (ETDEWEB)

    Giordano, Gennaro [Dept. of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Cole, Toby B. [Dept. of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Dept. of Medicine (Div. of Medical Genetics), University of Washington, Seattle, WA (United States); Dept. of Genome Sciences, University of Washington, Seattle, WA (United States); Furlong, Clement E. [Dept. of Medicine (Div. of Medical Genetics), University of Washington, Seattle, WA (United States); Dept. of Genome Sciences, University of Washington, Seattle, WA (United States); Costa, Lucio G., E-mail: lgcosta@u.washington.edu [Dept. of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Dept. of Human Anatomy, Pharmacology and Forensic Science, University of Parma Medical School, Parma (Italy)

    2011-11-15

    The aims of this study were to characterize the expression of paraoxonase 2 (PON2) in mouse brain and to assess its antioxidant properties. PON2 levels were highest in the lung, intestine, heart and liver, and lower in the brain; in all tissues, PON2 expression was higher in female than in male mice. PON2 knockout [PON2{sup -/-}] mice did not express any PON2, as expected. In the brain, the highest levels of PON2 were found in the substantia nigra, the nucleus accumbens and the striatum, with lower levels in the cerebral cortex, hippocampus, cerebellum and brainstem. A similar regional distribution of PON2 activity (measured by dihydrocoumarin hydrolysis) was also found. PON3 was not detected in any brain area, while PON1 was expressed at very low levels, and did not show any regional difference. PON2 levels were higher in astrocytes than in neurons isolated from all brain regions, and were highest in cells from the striatum. PON2 activity and mRNA levels followed a similar pattern. Brain PON2 levels were highest around birth, and gradually declined. Subcellular distribution experiments indicated that PON2 is primarily expressed in microsomes and in mitochondria. The toxicity in neurons and astrocytes of agents known to cause oxidative stress (DMNQ and H{sub 2}O{sub 2}) was higher in cells from PON2{sup -/-} mice than in the same cells from wild-type mice, despite similar glutathione levels. These results indicate that PON2 is expressed in the brain, and that higher levels are found in dopaminergic regions such as the striatum, suggesting that this enzyme may provide protection against oxidative stress-mediated neurotoxicity.

  12. AcEST: DK955225 [AcEST

    Lifescience Database Archive (English)

    Full Text Available protein kinase Nek3 OS=Ory... 32 2.3 sp|Q5F3M0|MED24_CHICK Mediator of RNA polymerase II transcriptio... 32 3.1 sp|P27169|PON1...909 LGSKTAGTHTQFVQWF 924 >sp|P27169|PON1_HUMAN Serum paraoxonase/arylesterase 1 OS=Homo sapiens GN=PON1 PE=1

  13. 香猪对氧磷酯酶基因家族的克隆及序列分析%Cloning and Identification of Paraoxonase Gene Family of Xiang Pig

    Institute of Scientific and Technical Information of China (English)

    李升; 牛熙; 徐霖; 冉雪琴; 王嘉福

    2012-01-01

    Three genes of paraoxonase (PON) family were separated from the liver of Xiang pig by reverse transcription polymerase chain reaction (RT-PCR) method. The cDNA of PON1, PON2 and PON3 were 1164, 1212 and 1080 base pairs in length, respectively. All of them contained complete open reading frame (ORF) coding for three precursors. The signal pep-tides were predicted to be 15 amino acids (aa) in PON1, 23 aa in PON2 and 23 aa in PON3 at the N-terminus of precursors. A nonsense mutation was found out from PON1 gene. Two changes in PON2 gene resulted in substitution from glutamine to ar-ginine at 234 site (Q234R) and valine to isoleucine at 269 site (V269I) in the matured PON2 protein. In PON3, only one mutation lead to substitution from arginine to histidine at 127 site (R127H) of the matured protein. All of the three replacements in mature proteins might change the microenvironment in the internal proteins based on the prediction of the three dimension structures of the matured proteins online. It suggested that the differences of the three paraoxonase genes might correlate to the stress resistance of Xiang pig.%采用RT-PCR技术,从香猪的肝脏总RNA中克隆了3个对氧磷酯酶(paraoxonase,PON)基因:PON1、PON2、PON3,其cDNA分别长1164、1212和1080 bp,各包含1个完整的开放阅读框,分别编码355、354、354个氨基酸组成的前体,其N-端的15、23、23个氨基酸为信号肽.香猪PON1基因中有1个碱基变异,不改变编码的氨基酸,为无义突变;香猪PON2基因中有2个碱基改变,导致成熟肽发生Q234R、V269I替换;香猪PON3基因中有1个碱基变化,使成熟肽出现R127H替换.经三维结构预测分析,这3个氨基酸位点的变化将影响蛋白质内部区域的微环境,影响对氧磷酯酶的功能,可能与香猪的抗逆性有一定的联系.

  14. The relationship between metabolic presbycusis and serum paraoxonase/arylesterase activity.

    Science.gov (United States)

    Keleş, Erol; Kapusuz, Zeliha; Gürsu, Mehmet Ferit; Karlıdag, Turgut; Kaygusuz, Irfan; Bulmuş, Funda Gülcü; Yalcın, Sinasi

    2014-01-01

    To determine the presence of a relationship between metabolic presbycusis and serum paraoxonase/arylesterase activity. A total of 30 patients who had been admitted to the Ear, Nose, and Throat (ENT) Clinic of Fırat University Medical Faculty and diagnosed as metabolic presbycusis were included in the study. The control group was composed of 30 healthy volunteers. Pure tone audiometry and impedencemeter were performed on all subjects included in the study at the audiometry laboratory of the ENT clinic. The presence of a regular hearing curve, a symmetrical sensorineural hearing loss more than 25 dB with preserved speech discrimination were accepted as criteria for metabolic presbycusis. Blood samples were drawn from the patients prior to the hearing tests. The sera were separated for measurements of total cholesterol, triglyceride, high-density lipoprotein, very low-density lipoprotein, low-density lipoprotein, human serum paraoxonase and arylesterase levels, respectively. No statistically significant difference was found between the patient and the control groups in terms of age and gender. Paraoxonase, arylesterase and paraoxonase/arylesterase, high-density lipoprotein levels were found to decrease in the study group and the difference was found to be statistically significant compared to the control group (P presbycusis. Furthermore, the results of this study make us think that there could be a relationship between metabolic presbycusis and cardiovascular diseases. In this case, metabolic presbycusis may be a determining parameter in the early diagnosis of cardiovascular diseases. We consider that this study may be the pioneer for further studies conducted with larger patient numbers.

  15. 对氧磷酶1基因Q192R多态性与中国汉族人缺血性卒中的相关性%Correlation between paraoxonase 1 Q192R polymorphism and ischemic stroke in Chinese Han population

    Institute of Scientific and Technical Information of China (English)

    周静; 章成國; 王玉凱; 邵燕; 謝海群; 崔金環

    2014-01-01

    Objective To investigate the correlation between large artery atherosclerotic stroke and paraoxonase 1 (PON1) Q192R polymorphism.Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the PON1 Q192R polymorphism of 120 patients with large artery atherosclerotic stroke (case group) and 117 healthy subjects (control group).Results There was significant difference in the genotype distribution of PON1 Q192R (x2 =18.727,P<0.001) and the allele frequency distribution (x2 =16.427,P <0.001) between the case group and the control group.Multivariate logistic regression analysis showed that RR genotype was an independent risk factor for large artery atherosclerotic stroke (odds ratio 1.377,95% confidence interval 1.032-2.185; P =0.026).Conclusions The allelic gene mutation rate of PON1 Q192R in patients with large artery atherosclerotic stroke was significantly higher than that in the healthy population.RR genotype is an independent risk factor for large artery atherosclerotic stroke.%目的 探讨对氧磷酶1(paraoxonase 1,PON1) Q192R基因多态性与大动脉粥样硬化性卒中的关系.方法 采用聚合酶链反应-限制性片段长度多态性法检测120例大动脉粥样硬化性卒中患者(病例组)和117名健康体检者(对照组)的PON1 Q192R基因多态性.结果 病例组和对照组PON1 Q192R基因型分布(x2=18.727,P<0.001)及等位基因频率分布(x2=16.427,P<0.001)均存在显著性差异.多变量logistic回归分析显示,RR基因型是大动脉粥样硬化性卒中的独立危险因素(优势比1.377,95%可信区间1.032~2.185;P=0.026).结论 大动脉粥样硬化性卒中患者的PON1 Q192R等位基因突变率显著性高于健康人群,RR基因型是大动脉粥样硬化性卒中的独立危险因素.

  16. Serum paraoxonase activity and protein thiols in patients with hyperlipidemia

    Institute of Scientific and Technical Information of China (English)

    Mungli Prakash; Jeevan K Shetty; Sudeshna Tripathy; Pannuri Vikram; Manish Verma

    2009-01-01

    Objective: In the present study we evaluated the paraoxonase activity and protein thiols level in south Indian population with newly diagnosed hyperlipidemia. Methods: The study was conducted on 55 newly diagnosed hyperlipidemic pa-tients and 57 healthy controls. Serum paraoxonase activity and protein thiols were estimated by spectrophotometeric method and lipid profile by enzymatic kinetic assay method. Results: Serum paraoxonase activity, protein thiols and high density lipoprotein levels were low and total cholesterol, triglycerides and low density lipoprutein levels were high in patients with hyperlipidemia compared to healthy controls ( P < 0.01 ). Serum paranxonase activity correlated positively with protein thiols and high density lipoprotein (P<0.01). Conclusion: Decreased paraoxonase activity and protein thiols were found in patients with hyperlipi-demia. This may indicate the susceptibility of this population to accelerated atherogenesis and protein oxidation.

  17. Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Atamer, Y. [Department of Medical Biochemistry, Faculty of Medicine, Dicle University, Diyarbakır (Turkey); Atamer, A. [Ministry of Health Haydarpaşa Numune Training and Research Hospital, Division of Gastroenterology, Department of Internal Medicine, Istanbul, Turkey, Division of Gastroenterology, Department of Internal Medicine, Ministry of Health Haydarpaşa Numune Training and Research Hospital, Istanbul (Turkey); Can, A.S. [Termal Professional School, Yalova University, Yalova (Turkey); Hekimoğlu, A. [Dicle University, Department of Pharmacology, Faculty of Medicine, Diyarbakir, Turkey, Department of Pharmacology, Faculty of Medicine, Dicle University, Diyarbakır (Turkey); Ilhan, N. [Firat University, Department of Medical Biochemistry, Faculty of Medicine, Elaziğ, Turkey, Department of Medical Biochemistry, Faculty of Medicine, Fırat University, Elazığ (Turkey); Yenice, N. [Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Harran University, Urfa (Turkey); Koçyiğit, Y. [Dicle University, Department of Physiology, Faculty of Medicine, Diyarbakir, Turkey, Department of Physiology, Faculty of Medicine, Dicle University, Diyarbakır (Turkey)

    2013-06-25

    Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m{sup 2}], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

  18. An Engineered Version of Human PON2 Opens the Way to Understand the Role of Its Post-Translational Modifications in Modulating Catalytic Activity

    Science.gov (United States)

    Mandrich, Luigi; Cerreta, Mariangela; Manco, Giuseppe

    2015-01-01

    The human paraoxonase 2 (PON2) has been described as a highly specific lactonase hydrolysing the quorum sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone (3OC12-HSL) and having secondary esterase but not phosphotriesterase activity, in contrast with the related enzymes PON1 and PON3. It has been suggested that PON2 enzyme activity is dependent on glycosylation and its N-terminal region has been recently demonstrated to be a transmembrane domain mediating association to membranes. In the present study we describe a mutated form of PON2, lacking the above N-terminal region, which has been further stabilized by the insertion of six amino acidic substitutions. The engineered version, hence forth called rPON2, has been over-expressed in E.coli, refolded from inclusion bodies and purified, yielding an enzyme with the same characteristics as the full length enzyme. Therefore the first conclusion of this work was that the catalytic activity is independent from the N-terminus and protein glycosylation. The kinetic characterization confirmed the primary activity on 3OC12-HSL; accordingly, in vitro experiments of inhibition of the biofilm formed by Pseudomonas aeruginosa (PAO1) have demonstrated that rPON2 is more effective than PON1. In addition, we observed small but significant activity against organophosphorothiotes pesticides, m-parathion, coumaphos and malathion.The availability of fair amount of active protein allowed to pinpoint, by mass-spectrometry, ubiquitination of Lys 168 induced in rPON2 by HeLa extract and to correlate such post-translational modification to the modulation of catalytic activity. A mutational analysis of the modified residue confirmed the result. PMID:26656916

  19. 血清对氧磷酯酶-1及氧化低密度脂蛋白在缺血性脑卒中的临床意义%The clinical significance of serum paraoxonase-1 activity, oxidized low-density lipoprotein level in ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    朱卫香; 刘彦敏; 张砚卿; 杜国辉; 张琳琳

    2015-01-01

    目的::探讨急性缺血性脑卒中患者血清对氧磷酯酶-1(PON-1)活性和氧化低密度脂蛋白(ox-LDL)水平的变化及其临床意义。方法:选择急性缺血性脑卒中患者96例及正常对照组72名,采用对硝基苯酚为底物的速率法和酶联免疫吸附法分别测定血清PON-1、ox-LDL,同时检测2组的总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇等生化指标并进行对比;探讨PON-1、ox-LDL与急性缺血性脑卒中的关系。结果:缺血性脑卒中组血清PON-1和高密度脂蛋白胆固醇均明显低于对照组,ox-LDL和低密度脂蛋白胆固醇明显高于对照组(P<0.01);大梗死组血清PON-1活性均低于中梗死组和小梗死组(P<0.05和P<0.01);而大梗死组ox-LDL水平均明显高于中梗死组和小梗死组(P<0.01);神经功能重度损伤组患者血清PON-1活性均明显低于轻、中度损伤组(P<0.01),而血清ox-LDL水平均显著高于轻、中度损伤组(P<0.01)。相关分析显示:PON-1与ox-LDL呈负相关关系(P<0.01)。结论:急性缺血性脑卒中患者PON-1活性降低,导致抗氧化能力减弱,使血清ox-LDL水平增加,这种改变可能是缺血性脑卒中重要的危险因素,对预测脑卒中风险有重要意义。%Objective:To investigate the changes of serum paraoxonase-1(PON-1) activity,oxidized low-density lipoprotein(ox-LDL) level in acute ischemic stroke patients and analyze the clinical significance. Methods:Ninety-six acute ischemic stroke cases and 72 health subjects were selected. Serum PON-1 activity was measured using paroxon as substrate and ox-LDL level was detected by enzyme-linked immuno sorbent assay method. Total cholesterol, triglyceride, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol levels were all measured in the two groups. The relationships of serum PON-1 activity,ox-LDL level and acute ischemic stroke were explored. Results:In ischemic stroke group

  20. Prenatal pesticide exposure and PON1 genotype associated with adolescent body fat distribution evaluated by dual X-ray absorptiometry (DXA)

    DEFF Research Database (Denmark)

    Tinggaard, J.; Wohlfahrt-Veje, C.; Husby, S.

    2016-01-01

    ) at age 10-15. Prenatal pesticide exposure was associated with increased total, android, and gynoid fat% (DXA) at age 10-15 years after adjustment for sex, socioeconomic status, and puberty (all β = 0.5 standard deviation score (SDS) p ... (total fat: β = 0.7 SDS, android-gynoid ratio: β = 0.1, both p ... circumference were found. Prenatal pesticide exposure was associated with higher adolescent body fat content, including android fat deposition, independent of puberty. Girls appeared more susceptible than boys. Furthermore, the association depended on maternal and child PON1 Q192R genotype....

  1. Relationships between PON1 Q192R polymorphism and clinical outcome of antiplatelet treatment after percutaneous coronary intervention: a meta-analysis.

    Science.gov (United States)

    Li, Ping; Bu, Shu-Hong; Lu, Xiao-Tong; Li, Li-Xia; Xu, A-Jing; Tang, Yue-Nian; Zhang, Jian

    2014-09-01

    This meta-analysis was performed to assess the relationships between the PON1 Q192R (rs662 T>C) polymorphism and the clinical outcome of antiplatelet treatment after percutaneous coronary intervention (PCI). A range of electronic databases were searched: Web of Science (1945-2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966-2013), EMBASE (1980-2013), CINAHL (1982-2013) and the Chinese Biomedical Database (CBM) (1982-2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. The crude odds ratio (OR) with their 95 % confidence interval (CI) were calculated. Six clinical cohort studies with a total number of 5,189 patients undergoing PCI for coronary heart disease were included. Our meta-analysis revealed that the PON1 Q192R polymorphism was correlated with an increased risk of major adverse cardiovascular events (MACE) in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.22, 95 % CI 1.04-1.43, P = 0.014; CT+CC vs. TT: OR = 1.38, 95 % CI 1.03-1.86, P = 0.029; CC vs. TT: OR = 1.45, 95 % CI 1.05-1.99, P = 0.024; respectively), especially among Asians. Furthermore, we found significantly positive correlations between the PON1 Q192R polymorphism and the incidence of stent thrombosis in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.42, 95 % CI 1.08-1.87, P = 0.011; CT+CC vs. TT: OR = 1.93, 95 % CI 1.01-3.67, P = 0.046; CC vs. TT: OR = 2.18, 95 % CI 1.09-4.35, P = 0.027; respectively). Our meta-analysis of clinical cohort studies provides evidence that the PON1 Q192R polymorphism may increase the risk of MACE and stent thrombosis in patients receiving antiplatelet treatment after PCI.

  2. Correlation between paraoxonase 1 Q192R polymorphism and cardiovascular adverse events after treatment with clopidogrel: a Meta-analysis%对氧磷酶1 Q192R基因多态性与氯吡格雷治疗后心血管不良事件相关性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    李新刚; 赵坤; 鲁燕侠; 赵志刚; 刘振华

    2015-01-01

    目的 评价对氧磷酶1(paraoxonase 1 ,PON1) Q192R基因多态性与氯吡格雷治疗后发生心血管不良事件的相关性. 方法 检索Web of Knowledge、PubMed、ScienceDirect、Embase、Cochrane Library,中国知网、万方数据库和维普中文科技期刊数据库(建库到2015年3月),收集符合纳入标准的前瞻性队列研究,采用Review Manager 5.3软件进行Meta分析.结果 采用比值比(OR)及其95%置信区间(CI)表示. 结果共有12项研究纳入Meta分析,患者共10 090例,其中亚洲人2 113例、欧洲人7 396例,北美洲人581例;PON1 Q192R基因型为QQ者4 096例,QR+ RR者5 994例.研究质量评价结果均为高质量.亚洲人群亚组中PON1 192QQ基因型者心血管事件发生率为8.1% (38/472),QR+ RR基因型者为10.8%(177/1 641),OR=1.06,95% CI为0.64 ~ 1.75,P=0.82;北美洲人群亚组中PON1 192QQ基因型者心血管事件发生率为10.4% (27/260),QR+ RR基因型者为10.9% (35/321),OR =0.95,95% CI为0.56 ~ 1.63,P=0.42;欧洲人群亚组中PON1 192QQ基因型者心血管事件发生率为6.5% (217/3 364),QR+ RR基因型者为5.6% (225/4 032),OR=1.21,95% CI为0.85 ~ 1.73,P=0.28.3个亚组合并后,PON1 192QQ基因型者心血管事件发生率为6.9% (282/4 096),QR+ RR基因型者为7.3% (437/5 994),OR=1.13,95% CI为0.89 ~ 1.44,P=0.33.漏斗图分析表明纳入研究不存在明显的发表偏倚或选择性偏倚. 结论 PON1 Q192R基因多态性与氯吡格雷治疗后的心血管不良事件之间没有明显相关性.%Objective To evaluate the correlation between paraoxonase 1 (PON1) Q192R polymorphism and cardiovascular adverse events in patients treated with clopidogrel.Methods Web of Knowledge, PubMed, ScienceDirect, Embase, Cochrane Library, China National Knowledge Infrastructure,Wanfang, and CQVIP were searched from the inception to March 2015 and prospective cohort studies in accordance with the criteria were collected.Meta-analysis was performed using Rev

  3. Lower paraoxonase 1 activity in Tunisian bipolar I patients

    Directory of Open Access Journals (Sweden)

    Araoud Manel

    2010-10-01

    Full Text Available Abstract Background The purpose of this study was to investigate the variations of paraoxonase activity and lipid profile in bipolar I patients, and the association of this activity with the sociodemographic, clinical and therapeutic characteristics of this population. Patients and methods Our study included 66 patients with bipolar I disorder and 64 controls aged 37.9 ± 12.6 and 36.3 ± 18.2 years, respectively. Paraoxonase activity was determined by kinetic methods; high-density lipoprotein cholesterol (c-HDL, low-density lipoprotein cholesterol (c-LDL, triglycerides and total cholesterol were determined by enzymatic methods; apolipoprotein (ApoA1, ApoB and lipoprotein (a (Lp(a were determined by immunoturbidimetry using Konelab 30 equipment (Thermo Scientific. Results Compared with controls, patients had a significantly lower paraoxonase activity and ApoA1 level, and significantly higher total cholesterol, c-LDL and Lp(a level and ApoB/ApoA1 ratio. Furthermore, paraoxonase activity was significantly correlated with c-HDL values (r = 0.5612; P Conclusions Bipolar patients had a significant decrease in paraoxonase activity and perturbations in their lipid profile that contribute to increased risk of cardiovascular diseases. Decrease in this activity was significantly associated with treatment with lithium but not with sociodemographic and clinical characteristics. Therefore, such patients require specific care, particularly with regard to their lipid profile.

  4. PON1 Q192R genetic variant and response to clopidogrel and prasugrel: pharmacokinetics, pharmacodynamics, and a meta-analysis of clinical outcomes.

    Science.gov (United States)

    Mega, Jessica L; Close, Sandra L; Wiviott, Stephen D; Man, Michael; Duvvuru, Suman; Walker, Joseph R; Sundseth, Scott S; Collet, Jean-Philippe; Delaney, Jessica T; Hulot, Jean-Sebastien; Murphy, Sabina A; Paré, Guillaume; Price, Matthew J; Sibbing, Dirk; Simon, Tabassome; Trenk, Dietmar; Antman, Elliott M; Sabatine, Marc S

    2016-04-01

    Clopidogrel and prasugrel are antiplatelet therapies commonly used to treat patients with cardiovascular disease. They are both pro-drugs requiring biotransformation into active metabolites. It has been proposed that a genetic variant Q192R (rs662 A>G) in PON1 significantly alters the biotransformation of clopidogrel and affects clinical outcomes; however, this assertion has limited support. The relationship between this variant and clinical outcomes with prasugrel has not been studied. We genotyped PON1 Q192R in 275 healthy subjects treated with clopidogrel or prasugrel and 2922 patients with an ACS undergoing PCI randomized to treatment with clopidogrel or prasugrel in the TRITON-TIMI 38 trial. A meta-analysis was performed including 13 studies and 16,760 clopidogrel-treated patients. Among clopidogrel-treated subjects, there were no associations between Q192R and active drug metabolite levels (P = 0.62) or change in platelet aggregation (P = 0.51). Consistent with these results, in clopidogrel-treated patients in TRITON-TIMI 38, there was no association between Q192R and the rates of CV death, myocardial infarction, or stroke (RR 11.2 %, QR 8.6 %, and QQ 9.3 %; P = 0.66) or stent thrombosis (RR 2.4 %, QR 0.7 %, and QQ 1.6 %, P = 0.30), with patients with the putative at-risk Q variant having numerically lower event rates. Likewise, among prasugrel-treated subjects, there were no associations between Q192R and active drug metabolite levels (P = 0.88), change in platelet aggregation (P = 0.97), or clinical outcomes (P = 0.72). In a meta-analysis, the Q variant was not significantly associated with MACE (QQ vs. RR 1.22, 95 % CI 0.84-1.76) or stent thrombosis (QQ vs. RR OR 1.36, 95 % CI 0.77-2.38). Furthermore, when restricted to the validation studies, the OR (95 % CI) for MACE and stent thrombosis were 0.99 (0.77-1.27) and 1.23 (0.74-2.03), respectively. In the present study, the Q192R genetic variant in PON1 was not associated with the pharmacologic or clinical

  5. Relationship between plasma paraoxonase-1 activity and oxygen free radical metabolism in patients with rheumatoid arthritis%类风湿关节炎患者血浆对氧磷酯酶-1活性与氧自由基代谢水平的相关性研究

    Institute of Scientific and Technical Information of China (English)

    张晓岚; 蒋兴亮; 邢艳; 刘素兰; 张均; 王光华; 罗书久

    2009-01-01

    Objective To investigate the relationship between plasma paraoxonase-1 (PON-1)activity and oxygen free radical (OFR)metabolism in patients with rheumatoid arthritis (RA). Methods The levels of plasma PON-1, oxidized low-density lipoprotein (ox-LDL), malondialdehyde (MDA), superoxide dismutase (SOD), glutathionperoxide (GSH-Px) and advanced oxidation protein products (AOPP) in 118 patients with RA and 56 healthy controls were measured. The correlative relationship between plasma PON-1 activity and OFR metabolism variables was analyzed. Results The levels of plasma PON-1, GSH-Px and SOD in RA patients were(122.2±24.1)kU/L,(156.4±32.2)U/L and (78.2±21.3)kU/L, and these were significantly lower than those in healthy controls (P<0.01). The levels of ox-LDL, MDA and AOPP in RA patients were (832.0±256.2)μg/L,(16.2±6.4) μmol/L and (342.3±118.1) μmol/L, and these were significantly higher than those in healthy controls (P<0.01). PON-1 activity was positively correlated with GSH-Px(r=0.781,P<0.01)and SOD (r=0.702,P<0.01), and it was negatively correlated with ox-LDL (r=-0.721,P<0.01), MDA ( r=-0.789,P<0.01) and AOPP (r=-0.679,P<0.01). Conclusions The plasma PON-1 activity in RA patients decreases significantly. PON-1 may participate in the pathophysiologic process of RA through the reduction of antioxidant properties.%目的 探讨类风湿关节炎(RA)患者血浆对氧磷酯酶-1(PON-1)活性与氧自由基代谢水平的关系. 方法检测118 例RA患者和56名健康对照者血浆PON-1活性、氧化修饰低密度脂蛋白(ox-LDL)、丙二醛(MDA)含量、超氧化物歧化酶(SOD)和循环谷胱苷肽过氧化物酶(GSH-Px)活性及晚期蛋白质氧化产物(AOPP)水平,分析PON-1活性与氧自由基代谢水平的关系. 结果 RA患者血浆PON-1、SOD、GSH-Px活性分别为(122.2±24.1)kU/L、(78.2±21.3)kU/L 、(156.4±32.2)U/L,低于对照组(P<0.01).ox-LDL、AOPP、MDA水平分别为(832.0±256.2)μg/L、(342.3±118.1) μmol/L、(16.2±6.4)

  6. Serum paraoxonase activity and lipid hydroperoxide levels in adult ...

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... different substrates.16 First, the rate of hydrolysis of paraoxon was ... when p value was less than 0.05. ... parameters, and serum LOOH levels, paraoxonase .... inhibition of cell growth. ... Hambrecht R, Wolf A, Gielen S, et al.

  7. Correlation between Cholinesterase and Paraoxonase 1 Activities: Case Series of Pesticide Poisoning Subjects

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    S Austin Richard

    2013-08-01

    Full Text Available Introduction: Acute exposure to pesticide due to suicidal poisoning is the most extensive cause of pesticide exposure, compared with all other causes including agricultural or industrial exposure. Organophosphate (OP and carbamate group of pesticides can inhibit acetylcholinesterase; on the other hand, paraoxonase1 can detoxify organophosphate poisoning by hydrolyzing organophosphate metabolites. Methods: We have compared the serum paraoxonase1 status and cholinesterase activity of subjects who attempted to commit suicide by consuming OP pesticide. Cholinesterase and paraoxonase1 activity were measured spectrophotometrically using butyrylthiocholine and phenyl acetate as substrates, respectively. Results: A positive correlation was found between serum paraoxonase1 activity and cholinesterase activity among pesticide consumed subjects. Conclusion: Our results suggest that subjects with higher paraoxonase1 activity may have a better chance of detoxifying the lethal effect of acute organophosphate poisoning.

  8. The determination of Q192R polymorphism of paraoxonase 1 by using non-toxic substrate p-nitrophenylacetate

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    M R Mogarekar

    2013-01-01

    Conclusion: The Q192R polymorphism of PON1 by using non-toxic substrate p-nitrophenylacetate showed trimodal distribution of QQ (homozygous, QR (heterozygous, and RR (homozygous phenotype and it is comparable with reference method. This method can be used for PON1 phenotype in different pathological and complex disease conditions.

  9. Paraoxonase and arylesterase activities in children with iron deficiency anemia and vitamin B12 deficiency anemia.

    Science.gov (United States)

    Koc, Ahmet; Cengiz, Murad; Ozdemir, Zeynep Canan; Celik, Hakim

    2012-05-01

    Paraoxonase-1 is an esterase enzyme and it has 3 types of activity, namely paraoxonase, arylesterase, and diazoxonase. It has been reported that paraoxonase-1 deficiency is related to increased susceptibility to development of atherosclerosis and cardiovascular disease. The aim of this study was to investigate serum paraoxonase and arylesterase activities in children with iron deficiency anemia and vitamin B(12) deficiency anemia. Thirty children with iron deficiency anemia, 30 children with vitamin B(12) deficiency anemia, and 40 healthy children aged 6 months to 6 years were enrolled in this study. Serum paraoxonase and arylesterase activities were measured with a spectrophotometer by using commercially available kits. Mean paraoxonase and arylesterase activities in vitamin B(12) deficiency anemia group (103 ± 73 and 102 ± 41 U/L, respectively) were significantly lower than mean activities of control group (188 ± 100 and 147 ± 34 U/L, respectively; P iron deficiency anemia group (165 ± 103 and 138 ± 39 U/L, respectively; P iron deficiency anemia and control groups (P > .05). Paraoxonase and arylesterase activities significantly increased after treatment with vitamin B(12) in vitamin B(12) deficiency anemia; however, there were no significant changes in the activities of these enzymes after iron treatment in iron deficiency anemia group. Important correlations were found between vitamin B(12) levels and both paraoxonase and arylesterase activities (r = .367, P deficiency anemia causes important reductions in paraoxonase and arylesterase activities, and after vitamin B(12) therapy the activities of these enzymes returned to near-normal levels.

  10. Exploring the aryl esterase catalysis of paraoxonase-1 through solvent kinetic isotope effects and phosphonate-based isosteric analogues of the tetrahedral reaction intermediate.

    Science.gov (United States)

    Bavec, Aljoša; Knez, Damijan; Makovec, Tomaž; Stojan, Jure; Gobec, Stanislav; Goličnik, Marko

    2014-11-01

    Although a recent study of Debord et al. in Biochimie (2014; 97:72-77) described the thermodynamics of the catalysed hydrolysis of phenyl acetate by human paraoxonase-1, the mechanistic details along the reaction route of this enzyme remain unclear. Therefore, we briefly present the solvent kinetic isotope effects on the phenyl acetate esterase activity of paraoxonase-1 and its inhibition with the phenyl methylphosphonate anion, which is a stable isosteric analogue that mimics the high-energy tetrahedral intermediate on the hydroxide-promoted hydrolysis pathway. The data show normal isotope effects, while proton inventory analysis indicates that two protons contribute to the kinetic isotope effect. Coherently, moderate competitive inhibition with the phenyl methylphosphonate anion reveals that the rate-limiting transition state suboptimally resembles the tetrahedral intermediate. The implications of these findings can be attributed to two possible reaction mechanisms that might occur during the paraoxonase-1-catalysed hydrolysis of phenyl acetate. Copyright © 2014 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

  11. No influence of increased intake of orange and blackcurrant juices and dietary amounts of vitamin E on paraoxonase-1 activity in patients with peripheral arterial disease

    DEFF Research Database (Denmark)

    Dalgård, Christine; Christiansen, Lene; Jonung, Torbjörn

    2007-01-01

    by dietary factors like the antioxidants. AIM OF THE STUDY: We examined the effect of antioxidant-rich orange and blackcurrant juices and vitamin E supplement on PON1 activity in patients with peripheral arterial disease. Furthermore, we studied whether genetic polymorphisms in the PON1 gene predicted...... the change in PON1 activity. METHODS: The study was designed as a cross-over trial with 48 participants who received two of the four possible treatments: (1) 250 ml orange juice and 250 ml blackcurrant juice; (2) 15 mg vitamin E; (3) 250 ml orange juice and 250 ml blackcurrant juice and 15 mg vitamin E...... significant interaction was observed between treatment and PON1 genotype, such that PON1 activity increased after juice alone in patients carrying the PON1 L55-allele. Results need to be interpreted with care since the study population was relatively small. CONCLUSION: Consumption of orange and blackcurrant...

  12. The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women's Heart and Health cohort study and a meta-analysis

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    Kiessling Matthew

    2004-06-01

    Full Text Available Abstract Background There have been inconsistent results from case-control studies assessing the association of the PON1 Q192R polymorphism with coronary heart disease (CHD. Most studies have included predominantly men and the association in women is unclear. Since lipid levels vary between the sexes the antioxidant effect of PON1 and any genes associated with it may also vary by sex. We have examined the association of the PON1 Q192R polymorphism with CHD in a large cohort of British women and combined the results from our cohort study with those from all other published studies. Results The distribution of genotypes was the same among women with CHD and those without disease. The odds ratio (95% confidence interval of having CHD comparing those with either the QR or RR genotype to those with QQ genotype (dominant model of association was 1.03 (0.89, 1.21 and the per allele odds ratio was 0.98 (0.95, 1.01. In a meta-analysis of this and 38 other published studies (10,738 cases and 17,068 controls the pooled odds ratio for the dominant effect was 1.14 (1.08, 1.20 and for the per allele effect was 1.10 (1.06, 1.13. There was evidence of small study bias in the meta-analyses and the dominant effect among those studies with 500 or more cases was 1.05 (0.96, 1.15. Ethnicity and reporting of whether the genotyping was done blind to the participants clinical status also contributed to heterogeneity between studies, but there was no difference in effect between studies with 50% or more women compared to those with fewer women and no difference between studies of healthy populations compared to those at high risk (with diabetes, renal disease of familial hypercholesterolaemia. Conclusion There is no robust evidence that the PON1 Q192R polymorphism is associated with CHD risk in Caucasian women or men.

  13. Increased Antioxidant Quality Versus Lower Quantity Of High Density Lipoprotein In Benign Prostatic Hyperplasia

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    Aydin Ozgur

    2015-10-01

    Full Text Available Background: Oxidative stress may be involved in the pathogenesis of every human disease. To understand its possible role in benign prostatic hyperplasia (BPH, we measured the overall oxidative status of patients with BPH and the serum activity of the high density lipoprotein (HDL-related antioxidant enzymes paraoxonase 1 (PON1 and arylesterase (ARE.

  14. Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport.

    Science.gov (United States)

    Nagarajan, Arvindhan; Dogra, Shaillay Kumar; Sun, Lisha; Gandotra, Neeru; Ho, Thuy; Cai, Guoping; Cline, Gary; Kumar, Priti; Cowles, Robert A; Wajapeyee, Narendra

    2017-08-17

    Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via stomatin. The loss of PON2 initiates the cellular starvation response and activates AMP-activated protein kinase (AMPK). In turn, AMPK activates FOXO3A and its transcriptional target, PUMA, which induces anoikis to suppress PDAC tumor growth and metastasis. Pharmacological or genetic activation of AMPK, similar to PON2 inhibition, blocks PDAC tumor growth. Collectively, our results identify PON2 as a new modulator of glucose transport that regulates a pharmacologically tractable pathway necessary for PDAC tumor growth and metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Increased N7-methyldeoxyguanosine DNA adducts after occupational exposure to pesticides and influence of genetic polymorphisms of paraoxonase-1 and glutathione S-transferase M1 and T1.

    Science.gov (United States)

    Gómez-Martín, Antonio; Altakroni, Bashar; Lozano-Paniagua, David; Margison, Geoffrey P; de Vocht, Frank; Povey, Andrew C; Hernández, Antonio F

    2015-06-01

    There are concerns about genetic risks associated with long-term exposure to pesticides as these compounds may damage DNA, resulting in mutations that eventually lead to cancer, neurological, and reproductive adverse health effects. This study assessed DNA damage in intensive agricultural workers exposed to pesticides by determining the levels of N7-methyldeoxyguanosine (N7-MedG), an adduct known to be a robust biomarker of recent exposure to chemical methylating agents. A cohort of 39 plastic greenhouse workers was assessed for changes in lymphocyte DNA N7-MedG levels between low level and high level exposures during the course of a spraying season. The contributions of genetic polymorphisms of the pesticide-metabolizing enzymes paraoxonase-1 (PON1) and the glutathione S-transferases, GSTM1 and GSTT1, on N7-MedG levels and other potential confounders were also assessed. N7-MedG increased in the period of high pesticide exposure as compared to the low exposure period (0.23 and 0.18 µmol N7-MedG/mol dG for the unadjusted and adjusted linear mixed models, P = 0.02 and 0.08, respectively). Significant decreased levels of erythrocyte acetylcholinesterase and plasma cholinesterase were observed in the high versus low exposure period in both the unadjusted (2.85 U/g hemoglobin and 213.13 U/L, respectively) and adjusted linear mixed models (2.99 U/g hemoglobin and 230.77 U/L, respectively), indicating pesticide intake. In intensive agriculture workers, higher pesticide exposure increased DNA alkylation levels, further demonstrating the genotoxicity of pesticides in man. In addition, pesticide-exposed individuals with inherited susceptible metabolic genotypes (particularly, null genotype for GSTM1 and the PON1 192R allele) appear to have an increased risk of genotoxic DNA damage. Environ. Mol. Mutagen. 56:437-445, 2015. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

  16. Paraoxonase activity in sera from Piaractus mesopotamicus Holmberg (Characidae and Hypostomus punctatus Valenciennes (Siluridae

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    Vera Lucia F. Cunha Bastos

    1998-01-01

    Full Text Available A paraoxonase activity present in serum of two Brazilian fish species was consistently assayed at pH 8.5 using 7.5 mM paraoxon final concentration. The paraoxonase activity was more activated by 0.5 M NaCl in serum of Piaractus mesopotanricus Holmberg, 1887 (pacu than in serum of Hypostomus punctatus Valenciennes, 1840 (cascudo. Apparent values of K M were 3.3 x 10-3 M for cascudo and pacu paraoxonase activity in the presence of 0.5 M NaCl. Apparent maximum velocity values calculated in the presence of 0.5 M NaCl were 6.1 and 6.5 nmole/min/mL of serum for cascudo and pacu, respectively. Vmax/K M ratio values of determinations in the presence and absence of 0.5 M NaCl showed that NaCl had a more evident effect on increasing the affinity of serum paraoxonase for paraoxon in pacu serum. Young specimens of pacu showed a marked decreased paraoxonase serum activity when kept in tanks treated with 0.25 ppm methyl-parathion.

  17. Paraoxonase-1 inhibits oxidized low-density lipoprotein-induced metabolic alterations and apoptosis in endothelial cells: a nondirected metabolomic study.

    Science.gov (United States)

    García-Heredia, Anabel; Marsillach, Judit; Rull, Anna; Triguero, Iris; Fort, Isabel; Mackness, Bharti; Mackness, Michael; Shih, Diana M; Joven, Jorge; Camps, Jordi

    2013-01-01

    We studied the influence of PON1 on metabolic alterations induced by oxidized LDL when incubated with endothelial cells. HUVEC cells were incubated with native LDL, oxidized LDL, oxidized LDL plus HDL from wild type mice, and oxidized LDL plus HDL from PON1-deficient mice. Results showed alterations in carbohydrate and phospholipid metabolism and increased apoptosis in cells incubated with oxidized LDL. These changes were partially prevented by wild type mouse HDL, but the effects were less effective with HDL from PON1-deficient mice. Our results suggest that PON1 may play a significant role in endothelial cell survival by protecting cells from alterations in the respiratory chain induced by oxidized LDL. These results extend current knowledge on the protective role of HDL and PON1 against oxidation and apoptosis in endothelial cells.

  18. Interrelationships between paraoxonase-1 and monocyte chemoattractant protein-1 in the regulation of hepatic inflammation.

    Science.gov (United States)

    Camps, Jordi; Marsillach, Judit; Rull, Anna; Alonso-Villaverde, Carlos; Joven, Jorge

    2010-01-01

    Oxidative stress and inflammation play a central role in the onset and development of liver diseases irrespective of the agent causing the hepatic impairment. The monocyte chemoattractant protein-1 is intimately involved in the inflammatory reaction and is directly correlated with the degree of hepatic inflammation in patients with chronic liver disease. Recent studies showed that hepatic paraoxonase-1 may counteract the production of the monocyte chemoattractant protein-1, thus playing an anti-inflammatory role. The current review summarises experiments suggesting how paraoxonase-1 activity and expression are altered in liver diseases, and their relationships with the monocyte chemoattractant protein-1 and inflammation.

  19. Association of paraoxonase polymorphisms and serum homocysteine thiolactone complex with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    秦勤

    2006-01-01

    Objective To investigate the relationship between paraoxonase (PON) polymorphisms and serum homocysteine thiolactone (HTL) and coronary heart diseases. Method In this prospective study, serum complex of HTL levels using ELISA, and the level of serum Hcy using high pressure liquid chromatography (HPLC) , de-

  20. Evaluation of paraoxonase, malondialdehyde, and lipoprotein levels in patients with asymptomatic cholelithiasis.

    Science.gov (United States)

    Atamer, Aytac; Kurdas-Ovunc, Ayse O; Yesil, Atakan; Atamer, Yildiz

    2014-01-01

    To compare lipoprotein and malondialdehyde levels and paraoxonase-1 activity between subjects with asymptomatic cholelithiasis and controls. Eighty subjects with asymptomatic cholelithiasis (55 women, 25 men, mean age: 51, SD 14 years) and 40 control subjects without cholelithiasis (25 women, 25 men, mean age: 51, SD 12 years) were enrolled to the study. Serum paraoxonase activity, lipoproteins, and malondialdehyde were measured. In the cholelithiasis group, serum total cholesterol, low-density lipoprotein cholesterol, and malondialdehyde were significantly higher and high-density lipoprotein cholesterol (HDL-C) and paraoxonase-1 were significantly lower than the controls. In cholelithiasis patients with serum glucose level>100 mg/dL, body mass index, serum total cholesterol, triglyceride (TG), and malondialdehyde levels were significantly higher than cholelithiasis patients with serum glucose level100 mg/dL. In cholelithiasis patients with TG>150 mg/dL, mean age, body mass index, glucose, total cholesterol, and malondialdehyde were significantly higher than in cholelithiasis patients with TGcholelithiasis subgroup with TG>150 mg/dL, HDL-C level and paraoxonase-1 activity were lower than in the cholelithiasis subgroup with TGcholelithiasis have evidence of increased lipid peroxidation and decreased antioxidant capacity. Patients with asymptomatic cholelithiasis with components of the metabolic syndrome have more lipid peroxidation and less antioxidant capacity than patients with asymptomatic cholelithiasis but without the components of the metabolic syndrome.

  1. Expression of PPARγ and paraoxonase 2 correlated with Pseudomonas aeruginosa infection in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Phoebe E Griffin

    Full Text Available The Pseudomonas aeruginosa quorum sensing signal molecule N-3-oxododecanoyl-l-homoserine lactone (3OC(12HSL can inhibit function of the mammalian anti-inflammatory transcription factor peroxisome proliferator activated receptor (PPARγ, and can be degraded by human paraoxonase (PON2. Because 3OC(12HSL is detected in lungs of cystic fibrosis (CF patients infected with P. aeruginosa, we investigated the relationship between P. aeruginosa infection and gene expression of PPARγ and PON2 in bronchoalveolar lavage fluid (BALF of children with CF. Total RNA was extracted from cell pellets of BALF from 43 children aged 6 months-5 years and analyzed by reverse transcription-quantitative real time PCR for gene expression of PPARγ, PON2, and P. aeruginosa lasI, the 3OC(12HSL synthase. Patients with culture-confirmed P. aeruginosa infection had significantly lower gene expression of PPARγ and PON2 than patients without P. aeruginosa infection. All samples that were culture-positive for P. aeruginosa were also positive for lasI expression. There was no significant difference in PPARγ or PON2 expression between patients without culture-detectable infection and those with non-Pseudomonal bacterial infection, so reduced expression was specifically associated with P. aeruginosa infection. Expression of both PPARγ and PON2 was inversely correlated with neutrophil counts in BALF, but showed no correlation with other variables evaluated. Thus, lower PPARγ and PON2 gene expression in the BALF of children with CF is associated specifically with P. aeruginosa infection and neutrophilia. We cannot differentiate whether this is a cause or the effect of P. aeruginosa infection, but propose that the level of expression of these genes may be a marker for susceptibility to early acquisition of P. aeruginosa in children with CF.

  2. Serum paraoxonase-I activity is unaffected by short-term administration of simvastatin, bezafibrate, and their combination in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Dullaart, R. P. F.; de Vries, R.; Voorbij, H. A. M.; Sluiter, W. J.; van Tol, A.

    Background The high-density lipoprotein (HDL)-associated anti-oxidative and anti-inflammatory enzyme, paraoxonase-I, has been found previously to be lower in type 2 diabetes mellitus. We studied whether statin and fibrate treatment, alone and in combination, affect serum paraoxonase-I activity in

  3. Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State

    Science.gov (United States)

    Koren-Gluzer, Marie; Rosenblat, Mira; Hayek, Tony

    2015-01-01

    Inflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1) or anti-inflammatory (M2). Paraoxonase 2 (PON2) is expressed in macrophages, and it was shown to protect against atherosclerosis. Thus, the aim of our study was to analyze the direct effect of PON2 on macrophage inflammatory phenotypes. Ex vivo studies were performed with murine peritoneal macrophages (MPM) harvested from control C57BL/6 and PON2-deficient (PON2KO) mice. PON2KO MPM showed an enhanced proinflammatory phenotype compared to the control, both in the basal state and following M1 activation by IFNγ and lipopolysaccharide (LPS). In parallel, PON2KO MPM also showed reduced anti-inflammatory responses in the basal state and also following M2 activation by IL-4. Moreover, the PON2-null MPM demonstrated enhanced phagocytosis and reactive oxygen species (ROS) production in the basal state and following M1 activation. The direct effect of PON2 was shown by transfecting human PON2 (hPON2) into PON2KO MPM. PON2 transfection attenuated the macrophages' response to M1 activation and enhanced M2 response. These PON2 effects were associated with attenuation of macrophages' abilities to phagocyte and to generate ROS. We conclude that PON2 promotes an M1 to M2 switch in macrophage phenotypes. PMID:26779262

  4. Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State

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    Marie Koren-Gluzer

    2015-01-01

    Full Text Available Inflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1 or anti-inflammatory (M2. Paraoxonase 2 (PON2 is expressed in macrophages, and it was shown to protect against atherosclerosis. Thus, the aim of our study was to analyze the direct effect of PON2 on macrophage inflammatory phenotypes. Ex vivo studies were performed with murine peritoneal macrophages (MPM harvested from control C57BL/6 and PON2-deficient (PON2KO mice. PON2KO MPM showed an enhanced proinflammatory phenotype compared to the control, both in the basal state and following M1 activation by IFNγ and lipopolysaccharide (LPS. In parallel, PON2KO MPM also showed reduced anti-inflammatory responses in the basal state and also following M2 activation by IL-4. Moreover, the PON2-null MPM demonstrated enhanced phagocytosis and reactive oxygen species (ROS production in the basal state and following M1 activation. The direct effect of PON2 was shown by transfecting human PON2 (hPON2 into PON2KO MPM. PON2 transfection attenuated the macrophages’ response to M1 activation and enhanced M2 response. These PON2 effects were associated with attenuation of macrophages’ abilities to phagocyte and to generate ROS. We conclude that PON2 promotes an M1 to M2 switch in macrophage phenotypes.

  5. 汉族人芳香二烷基磷酸酯酶启动子-162 A/G基因多态性与冠心病发病的关系%Relationship between PON1-162A/G gene polymorphism and CHD

    Institute of Scientific and Technical Information of China (English)

    张颖; 周新; 霍麟; 杜寒松

    2004-01-01

    目的研究湖北地区汉族人芳香二烷基磷酸酯酶(paraoxonasc,PON1)启动子基因-162位Ala-Gly基因多态性与冠心病(CHD)发病的关系.方法应用多聚酶链反应-限制性片段长度多态性的分析方法(PCR-RELP)检测湖北汉族地区CHD患者及正常对照组PON1基因启动子-162位点的多态性,血脂用酶法测定.结果 PON1启动子-162位点存在多态性,有AA,AG,GG 3种基因型.128例正常人中AA基因型占4.7%,AG基因型占20.3%,GG基因型占75.0%,而CHD组与对照组-162 Ala-Gly基因型分布总体构成比差异无显著性.对照组和CHD组PON基因G等位基因频率分别为0.852和0.913,差异也无显著性(P>0.05).结论未发现PON1启动子基因-162位Ala-Gly多态性与中国人CHD有关.

  6. Autopsy and postmortem examination case study on genetic risk factors for cardiac death: Polymorphisms of endothelial nitric oxide synthase gene Glu298asp variant and T-786c mutation, human paraoxonas

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    Ameno Kiyoshi

    2006-01-01

    Full Text Available Background/Aim. The Glu298Asp variant in exon 7 and T-786C mutation in the 5'-flanking region of the endothelial nitric oxide synthase (eNOS gene, paraoxonase I gene (PON1, and α2β- adrenergic receptor gene (α2β-AR have been reported to be genetic risk factors for coronary heart disease (CHD. The aim of this study was to investigate the effects of these four genetic polymorphisms on the probability of death due to CHD, using data obtained from medico-legal autopsies. Methods. Blood samples from three groups: healthy controls, dead cases with CHD and without CHD (the latter as a control for dead cases were used. After DNA extraction, genotyping was performed by polymerase chain reaction − restriction fragment length polymorphism (PCR-RFLP test. Results. The frequency of the T allele in Glu298Asp variant in the dead cases with CHD was significantly higher than that in the healthy control (p < 0.001, OR = 4.47 and that in the dead cases without CHD (p < 0.001, OR = 7.62. The gene frequency of PON1 was significantly different (p = 0.007 between dead cases with and without CHD, and was also significantly different (p = 0.025 between the healthy control and dead cases without CHD. The gene frequency of PON1 was not significantly different (p = 0.401 between the healthy controls and dead cases with CHD. Hence this gene was not associated with death due to CHD. The other polymorphisms (T- 786C mutation, α2β-AR also showed no effect on death due to CHD. Conclusion. The polymorphism of Glu298Asp eNOS gene in dead cases may be useful for determining the cause of death in CHD cases in the Japanese population.

  7. Correlation of serum paraoxonase activities in known cases of 130 elderly hypertensive South Asian aged 56-64 years - a hospital based study

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    Arun Kumar

    2014-02-01

    Full Text Available Objective: To evaluate paraoxonase activity, antioxidant status and lipid peroxidation in hypertensive participants and to address the hypothesis that oxidative modifications of lipids due to hypertension can cause changes in serum paraoxonase activities. Methods: The serum paraoxonase activities, antioxidants and lipid peroxidation were determined in 130 hypertensive participants and 130 age-sexes matched normotensive healthy volunteers served as control. Serum paraoxonase activities were measured by enzymatic kit. The glutathione peroxidase, superoxide dismutase and catalase activity were determined by standard methods. Malondialdehyde was measured by thiobarbituric acid reaction. Conjugated diene level was measured by Recknagel and Glende method. Serum uric acid, total bilirubin, serum albumin, serum ascorbic acid and lipid profile were analyzed by standard methods. Results: Total cholesterol, triglycerides, low-density lipoprotein cholesterol were significantly higher and high-density lipoprotein cholesterol were significantly lower in hypertensive patients when compared to normotensive healthy controls. The superoxide dismutase, glutathione peroxidase and catalase were significantly lower in hypertensive when compared with normotensive. Similar findings were observed in the levels of albumin, uric acid, bilirubin and ascorbic acid when hypertensives were compared with normotensive. The oxidative stress indicators namely malondialdehyde and conjugated diene were significantly higher and paraoxonase activity were significantly lower in hypertensive. Conclusions: Our study concludes that paraoxonase activities are bound to alter in hypertension which is caused due to interplay of several confounding factors namely oxidative stress, increased oxidized low-density lipoprotein and depletion of antioxidants.

  8. Effects of paraoxonase, arylesterase, ceruloplasmin, catalase, and myeloperoxidase activities on prognosis in pediatric patients with sepsis.

    Science.gov (United States)

    Ayar, Ganime; Atmaca, Yasemin Men; Alışık, Murat; Erel, Özcan

    2017-05-01

    The present study aimed to investigate the levels of paraoxonase (PON), stimulated paraoxonase (SPON), arylesterase (ARE), ceruloplasmin (CLP), myeloperoxidase (MPO), and catalase (CAT) in pediatric sepsis and to explore their effects on the prognosis of sepsis. Patients diagnosed with sepsis (n=33) and healthy controls (n=30) were included. PON, SPON, ARE, CLP, MPO, and CAT activities were measured in the sepsis and control groups. Additionally, the parameters were compared between survivors and non-survivors in the sepsis group. The levels of hemoglobin, white blood cell, platelet, lactate, and C-reactive protein were measured in the blood samples drawn from the patients with sepsis at diagnosis, at the 48th hour, and on day 7. The pediatric risk of mortality and pediatric logistic organ dysfunction scores of the patients were used for the estimation of severity of disease. Lower ARE (153.24 vs. 264.32U/L; psepsis group as compared to the control group. There was no difference between the groups in terms of PON or SPON levels. No difference was determined between the survivors and non-survivors in terms of any of the parameters. The present study determined that ARE, CLP, CAT, and MPO levels are different between the pediatric patients with sepsis and healthy controls. ARE level can be a potent biomarker for sepsis in critical patients in intensive care units. Further studies with larger samples are required to demonstrate the value of these parameters as prognostic biomarkers in pediatric sepsis. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  9. Positive clinical response to clopidogrel is independent of paraoxonase 1 Q192R and CYP2C19 genetic variants.

    Science.gov (United States)

    Martínez-Quintana, Efrén; Medina-Gil, José M; Rodríguez-González, Fayna; Garay-Sánchez, Paloma; Limiñana, José M; Saavedra, Pedro; Tugores, Antonio

    2014-08-01

    There is increasing controversy about the influence of serum paraoxonase type 1 and cytochrome CYP2C19 in the conversion of clopidogrel to its pharmaceutically active metabolite. The effect of concomitant medication with the proton pump inhibitor omeprazole has been also subject of intense scrutiny. We present a cohort of 263 patients receiving anti-platelet aggregation treatment with clopidogrel and aspirin for 1 year. The paraoxonase 1 gene Q192R variant along with the presence of CYP2C19*2 and *3 loss of function alleles, concomitant medication with proton pump inhibitors and known cardiovascular risk factors were examined to determine their influence in disease relapse due to an ischaemic event during the 12 month treatment period. The low number of patients suffering a relapse (20 out of 263), indicates that double anti-aggregation therapy with aspirin and clopidogrel was very effective in our patients. Among the relapsers, evidence of coronary heart disease was the most influencial factor affecting response to therapy, while the presence of the paraoxonase 1 Q192R variant, loss of function of CYP2C19, and concomitant medication with omeprazole were non-significant.

  10. High plasma C-reactive protein (CRP) is related to low paraoxonase-I (PON-I) activity independently of high leptin and low adiponectin in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; de Vries, Rindert; Sluiter, Wim J.; Voorbij, Hieronymus A. M.

    2009-01-01

    In type 2 diabetes mellitus, circulating C-reactive protein (CRP) is increased, whereas the high density lipoprotein (HDL)-associated, anti-oxidative and anti-inflammatory enzyme, paraoxonase-I, is decreased. Both high CRP and low paraoxonase-I activity may predict cardiovascular disease. It is unkn

  11. The effect of Omega-3 fatty acids on serum paraoxonase activity, vitamins A, E, and C in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Anis Kouchak

    2011-01-01

    Full Text Available Background: Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycemia. Studies showed paraoxonase activity, and vitamin C and A levels are decreased in diabetes. The effect of omega-3 fatty acids on serum paraoxonase activity and vitamins A, E, C in patients with type 2 diabetes is not fully understood. This study aimed to determine the effect of omega-3 fatty acids on paraoxonase activity, vitamins C, A and E levels in type 2 diabetic patients. Methods: In a double-blind, placebo controlled trial, 80 type 2 diabetic patients were randomly enrolled into the study. Study subjects received daily 2714 mg of omega-3 fatty acids or placebo for 8 weeks. Ten milliliter fasting blood was collected before and after treatments. Serum paraoxonase activity and vitamin C levels were measured by spectrophotometry. Vitamin A and vitamin E were measured using high performance liquid chromatography. Nutrient intake was estimated using 24-hours dietary recall questionnaire (for 2 days before and after treatments. Dietary data were analyzed using FPII. To compare the means of variables between the two groups, independent t-test was employed. Differences between variables before and after interventions were calculated using paired t-test. Results: Serum levels of paraoxonase activity were significantly increased after omega-3 intake (126.47 IU/ml vs. 180.13 IU/ml. However, omega-3 intake caused no significant change in serum vitamin A, C, and E. Conclusions: Supplementation of omega-3 fatty acids was found to increase paraoxonase activity in diabetic patients.

  12. STUDY ON THE RELATIONSHIP BETWEEN PARAOXONASE GENE POLYMORPHISM AND CORONARY ARTERIAL DISEASE IN NIDDM

    Institute of Scientific and Technical Information of China (English)

    尤蓓; 于金德; 陆林; 乐玮; 陶蓉; 何汝敏; 龚兰生

    2001-01-01

    Objective To ascertain the relationship between paraoxonase gene (PON) and the morbidity of coronary arterial disease (CAD) in Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients. Methods The exons of PON gene were screened by polymerase chain reaction-denaturing gradient gel electrophoresis in 49 NIDDM patients complicated with CAD, 49 NIDDM and 101 healthy control cases of Chinese population. Results Gln-Arg191 polymorphism of the PON gene was detected in Chinese with the A/B allele frequency 0.39 and 0.61 respectively. The genotype distribution (AA, AB and BB) of the PON gene polyrnorphism was significantly different between NIDDM patients complicated with CAD and controls (NIDDM and healthy subjects). The former had a significantly higher B allele frequency (0.79 vs 0.62 and 0.61, P <0.01 ). Conclusion Gln-Arg191 polymorphisrn of the PON gene is associated with CAD morbidity in Chinese NIDDM patients and B allele might be a risk factor.

  13. Antibodies toward high-density lipoprotein components inhibit paraoxonase activity in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Batuca, J R; Ames, P R J; Isenberg, D A; Alves, J Delgado

    2007-06-01

    Patients with systemic lupus erythematosus (SLE) have an increased incidence of vascular disease, and oxidative stress is recognized as an important feature in this condition, despite the underlying mechanisms not being fully understood. In these patients, an interaction between lipoproteins and the immune system has been suggested, but most studies have only looked at antibodies against oxidized low-density lipoproteins. This study was undertaken to determine the presence of antibodies directed against high-density lipoproteins (HDL) and to identify a possible association between these antibodies and paraoxonase (PON), an antioxidant enzyme present in HDL. Plasma from 55 patients with SLE was collected and IgG aHDL and antiapolipoprotein A-I (aApo A-I) antibodies were assessed by enzyme-linked immunosorbent assay. Standardization of the method was performed in a control population of 150 healthy subjects. Plasma levels above 5 standard deviations of the mean of the control population were considered positive. PON activity was assessed by quantification of p-nitrophenol formation (micromol/mL/min). Patients with SLE had higher titers of aHDL (P aHDL and aApo A-I antibodies (r = 0.61; P aHDL and aApo A-I antibodies in patients with SLE. These antibodies were associated with reduced PON activity in plasma, and the in vitro inhibition assay confirmed a direct inhibition of the enzyme activity.

  14. Structural Studies on Acetylcholinesterase and Paraoxonase Directed Towards Development of Therapeutic Biomolecules for the Treatment of Degenerative Diseases and Protection Against Chemical Threat Agents

    Science.gov (United States)

    Sussman, Joel L.; Silman, Israel

    Acetylcholinesterase and paraoxonase are important targets for treatment of degenerative diseases, Alzheimer's disease and atherosclerosis, respectively, both of which impose major burdens on the health care systems in Western society. Acetylcholinesterase is the target of lethal nerve agents, and paraoxonase is under consideration as a bioscavenger for their detoxification. Both are thus the subject of research and development in the context of nerve agent toxicology. The crystal structures of the two enzymes are described, and structure/function relationships are discussed in the context of drug development and of development of means of protection against chemical threats.

  15. Analysis on polymorphism of paraoxonase promotor in patients with coronary heart diseases%冠心病患者对氧磷酶启动子基因多态性分析

    Institute of Scientific and Technical Information of China (English)

    邵海琴; 张颖

    2007-01-01

    目的 探讨中国人对氧磷酶(PON1)基因-108C/T、-162A/G、-909C/G遗传多态性与冠心病(CHD)的关系.方法 应用多聚酶链反应(PCR)对武汉地区86例冠心病患者和128例相匹配的正常对照者PON1基因酶切位点的限制性片段长度多态性(RFLP)进行研究.结果 PON1-108C/T多态性位点基因型分布在CHD组和对照组间存在显著差异(P<0.05).PON1-162A/G、-909C/G多态性位点基因型频率和等位基因频率在两组间未见显著性差异(P>0.05).CHD不随三个多态性位点危险基因型个数的增加而发病率呈上升趋势.结论 PON1-108C/T、-162A/G、-909C/G基因多态性对CHD的影响无协同性.

  16. The Paraoxonase 1 Arylesterase Activity, Total Oxidative Stress, Nitric Oxide and Vitamin C Levels in Maternal Serum, and Their Relation to Birth Weight of Newborn.

    Science.gov (United States)

    Mogarekar, Mukund Ramchandra; Dhabe, Mahendra G; Gujrathi, Chanchal C

    2016-10-01

    Aim of this study is to find out clinical relevance of estimating PON1 arylesterase activity, total oxidative stress (TOS), nitric oxide (NO), and vitamin C levels in maternal serum for prediction of birth weight of newborn. We have investigated the PON1 arylesterase activity, TOS, NO, vitamin C, total protein, and albumin levels in 56 postnatal clinic patients having newborn weighing 2500 gm. Samples were collected immediately after delivery. PON1 arylesterase activity levels show significant decrease in cases as compared to controls (93.27 ± 13.76 kU/l vs. 112.77 ± 9.42 kU/l). Nitric oxide (nitrate + nitrite) levels are also found to be significantly decreased in cases with respect to controls (22.89 ± 2.65 umol/l vs. 24.73 ± 3.80 umol/l). Total oxidative stress is significantly increased in cases than in control subjects (23.34 ± 2.64 μmol H2O2 equiv./l vs. ± 21.43 ± 2.47 μmol H2O2 equiv/l). Vitamin C levels are also significantly decreased in cases as compared to controls (1.23 ± 0.25 mg/dl vs. 1.34 ± 0.28 mg/dl). Positive correlation between neonatal birth weight and maternal serum PON1 arylesterase activity (r = 0.682, p stress (r = -0.478, p levels with increased total oxidative stress in maternal serum may be considered as the additional risk factors for the development of low birth weight newborn.

  17. Human Paraoxonase Double Mutants Hydrolyze V and G Class Organophosphorus Nerve Agents

    Science.gov (United States)

    2013-01-01

    induced by seizures. Traditional pharmacological approaches to alleviate the effects of OP poisoning have reached a point where only modest incremental...using Prism 4.0 (GraphPad, La Jolla, CA). 3. Results and discussion Organophosphate insecticides like paraoxon are helpful in quickly determining OP...therapy of organophosphorus poisoning , Toxicology 233 (2007) 47–49. [5] M. Harel, A. Aharoni, L. Gaidukov, B. Brumshtein, O. Khersonsky, R. Meged, H. Dvir

  18. Dramatic Differences in Organophosphorus Hydrolase Activity between Human and Chimeric Recombinant Mammalian Paraoxonase-1 Enzymes

    Science.gov (United States)

    2009-01-01

    with phenyl acetate and paraoxonwere determined by Michaelis - Menten steady state kinetics . The data from four or more independent experiments were fit...paraoxon was followed atA412 for 20 min at room temperature as described above. The data were fit using Michaelis - Menten steady state kinetics to derive...for 4 h at room temperature as described above. The data were fit using Michaelis - Menten steady state kinetics to derive the KM and Vmax values of

  19. Paraoxonase 2 decreases renal reactive oxygen species production, lowers blood pressure, and mediates dopamine D2 receptor-induced inhibition of NADPH oxidase.

    Science.gov (United States)

    Yang, Yu; Zhang, Yanrong; Cuevas, Santiago; Villar, Van Anthony; Escano, Crisanto; D Asico, Laureano; Yu, Peiying; Grandy, David K; Felder, Robin A; Armando, Ines; Jose, Pedro A

    2012-08-01

    The dopamine D(2) receptor (D(2)R) regulates renal reactive oxygen species (ROS) production, and impaired D(2)R function results in ROS-dependent hypertension. Paraoxonase 2 (PON2), which belongs to the paraoxonase gene family, is expressed in various tissues, acting to protect against cellular oxidative stress. We hypothesized that PON2 may be involved in preventing excessive renal ROS production and thus may contribute to maintenance of normal blood pressure. Moreover, D(2)R may decrease ROS production, in part, through regulation of PON2. D(2)R colocalized with PON2 in the brush border of mouse renal proximal tubules. Renal PON2 protein was decreased (-33±6%) in D(2)(-/-) relative to D(2)(+/+) mice. Renal subcapsular infusion of PON2 siRNA decreased PON2 protein expression (-55%), increased renal oxidative stress (2.2-fold), associated with increased renal NADPH oxidase expression (Nox1, 1.9-fold; Nox2, 2.9-fold; and Nox4, 1.6-fold) and activity (1.9-fold), and elevated arterial blood pressure (systolic, 134±5 vs 93±6mmHg; diastolic, 97±4 vs 65±7mmHg; mean 113±4 vs 75±7mmHg). To determine the relevance of the PON2 and D(2)R interaction in humans, we studied human renal proximal tubule cells. Both D(2)R and PON2 were found in nonlipid and lipid rafts and physically interacted with each other. Treatment of these cells with the D(2)R/D(3)R agonist quinpirole (1μM, 24h) decreased ROS production (-35±6%), associated with decreased NADPH oxidase activity (-32±3%) and expression of Nox2 (-41±7%) and Nox4 (-47±8%) protein, and increased expression of PON2 mRNA (2.1-fold) and protein (1.6-fold) at 24h. Silencing PON2 (siRNA, 10nM, 48h) not only partially prevented the quinpirole-induced decrease in ROS production by 36%, but also increased basal ROS production (1.3-fold), which was associated with an increase in NADPH oxidase activity (1.4-fold) and expression of Nox2 (2.1-fold) and Nox4 (1.8-fold) protein. Inhibition of NADPH oxidase with diphenylene

  20. Acute phase proteins response in cats naturally infected with Hepatozoon felis and Babesia vogeli.

    Science.gov (United States)

    Vilhena, Hugo; Tvarijonaviciute, Asta; Cerón, José J; Vieira, Lisete; Pastor, Josep; Silvestre-Ferreira, Ana C

    2017-03-01

    The measurement of acute phase proteins (APP) is being increasingly used in human and veterinary medicine in diagnosis, prognosis, treatment monitoring, and in general health screening. However, information about the APP response in cats infected with agents of vector-borne diseases is lacking. The purpose of the study was to investigate the concentrations of serum amyloid A (SAA), haptoglobin (Hp), and paraoxonase-1 (PON1) in cats naturally infected with Hepatozoon felis and Babesia vogeli. Serum concentrations of SAA, Hp, and PON1 were determined in 19 cats naturally infected with H felis and in 11 cats naturally infected with B vogeli, and compared to concentrations in 10 healthy control cats. Serum Hp concentrations were significantly increased, and PON1 concentrations significantly decreased in symptomatic and asymptomatic cats infected with H felis and B vogeli when compared with healthy noninfected cats. In the H felis-infected population, concentrations of SAA and Hp were significantly increased in symptomatic cats when compared with asymptomatic animals. This study demonstrated differences in APP concentrations in cats infected with H felis and B vogeli. Therefore, Hp and PON1 concentrations could be helpful in discriminating healthy cats from cats with asymptomatic or symptomatic infection by these agents. © 2017 American Society for Veterinary Clinical Pathology.

  1. Ascorbic acid partly antagonizes resveratrol mediated heme oxygenase-1 but not paraoxonase-1 induction in cultured hepatocytes - role of the redox-regulated transcription factor Nrf2

    Directory of Open Access Journals (Sweden)

    Hori Osamu

    2011-01-01

    Full Text Available Abstract Background Both resveratrol and vitamin C (ascorbic acid are frequently used in complementary and alternative medicine. However, little is known about the underlying mechanisms for potential health benefits of resveratrol and its interactions with ascorbic acid. Methods The antioxidant enzymes heme oxygenase-1 and paraoxonase-1 were analysed for their mRNA and protein levels in HUH7 liver cells treated with 10 and 25 μmol/l resveratrol in the absence and presence of 100 and 1000 μmol/l ascorbic acid. Additionally the transactivation of the transcription factor Nrf2 and paraoxonase-1 were determined by reporter gene assays. Results Here, we demonstrate that resveratrol induces the antioxidant enzymes heme oxygenase-1 and paraoxonase-1 in cultured hepatocytes. Heme oxygenase-1 induction by resveratrol was accompanied by an increase in Nrf2 transactivation. Resveratrol mediated Nrf2 transactivation as well as heme oxygenase-1 induction were partly antagonized by 1000 μmol/l ascorbic acid. Conclusions Unlike heme oxygenase-1 (which is highly regulated by Nrf2 paraoxonase-1 (which exhibits fewer ARE/Nrf2 binding sites in its promoter induction by resveratrol was not counteracted by ascorbic acid. Addition of resveratrol to the cell culture medium produced relatively low levels of hydrogen peroxide which may be a positive hormetic redox-signal for Nrf2 dependent gene expression thereby driving heme oxygenase-1 induction. However, high concentrations of ascorbic acid manifold increased hydrogen peroxide production in the cell culture medium which may be a stress signal thereby disrupting the Nrf2 signalling pathway.

  2. Serum paraoxonase activity and oxidative stress and their relationship with obesity-related metabolic syndrome and non-alcoholic fatty liver disease in obese children and adolescents.

    Science.gov (United States)

    Torun, Emel; Gökçe, Selim; Ozgen, İlker Tolga; Aydın, Sinem; Cesur, Yasar

    2014-07-01

    Oxidative stress has been reported to be involved in the pathogenesis of metabolic disorders related with obesity. The aim of the study was to investigate the association of oxidative stress and paraoxonase activities with non-alcoholic fatty liver disease (NAFLD) as well as metabolic syndrome. A total of 109 obese children and adolescents and 44 healthy and lean control subjects were enrolled in the study. According to their ultrasonographic steatosis scores, they were classified into four groups as follows: healthy children; obese, non-NAFLD; obese, grade I-NAFLD; and obese, grade II-III NAFLD. The biochemical parameters and insulin resistance (HOMA-IR) were evaluated from fasting samples. The plasma total antioxidant status (TAS), total oxidant status (TOS), and serum paraoxonase activities were measured and then oxidative stress index (OSI) was calculated as the indicator of degree of oxidative stress. As the steatosis increased, the alanine aminotransferase, C-reactive protein, HOMA-IR, total cholesterol, and LDL cholesterol increased, whereas HDL cholesterol decreased. The TAS measurements were higher in the obese NAFLD group compared with that of the healthy control group. The TOS and OSI measurements did not differ between the groups. Paraoxonase activities increased significantly as steatosis increased. Among the children in this study, no relationship could be demonstrated between obesity with/without steatosis and oxidant/antioxidant status.

  3. Caenorhabditis elegans paraoxonase-like proteins control the functional expression of DEG/ENaC mechanosensory proteins

    Science.gov (United States)

    Chen, Yushu; Bharill, Shashank; Altun, Zeynep; O’Hagan, Robert; Coblitz, Brian; Isacoff, Ehud Y.; Chalfie, Martin

    2016-01-01

    Caenorhabditis elegans senses gentle touch via a mechanotransduction channel formed from the DEG/ENaC proteins MEC-4 and MEC-10. An additional protein, the paraoxonase-like protein MEC-6, is essential for transduction, and previous work suggested that MEC-6 was part of the transduction complex. We found that MEC-6 and a similar protein, POML-1, reside primarily in the endoplasmic reticulum and do not colocalize with MEC-4 on the plasma membrane in vivo. As with MEC-6, POML-1 is needed for touch sensitivity, the neurodegeneration caused by the mec-4(d) mutation, and the expression and distribution of MEC-4 in vivo. Both proteins are likely needed for the proper folding or assembly of MEC-4 channels in vivo as measured by FRET. MEC-6 detectably increases the rate of MEC-4 accumulation on the Xenopus oocyte plasma membrane. These results suggest that MEC-6 and POML-1 interact with MEC-4 to facilitate expression and localization of MEC-4 on the cell surface. Thus MEC-6 and POML-1 act more like chaperones for MEC-4 than channel components. PMID:26941331

  4. Chemokine ligand 2 and paraoxonase-1 in non-alcoholic fatty liver disease: The search for alternative causative factors.

    Science.gov (United States)

    Camps, Jordi; Joven, Jorge

    2015-03-14

    The incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) is constantly increasing. Despite this is apparently associated with the growing increase in obesity, insulin resistance and obesity-related metabolic disturbances their presence is not a necessary or sufficient condition to explain the accumulation of fat in the liver. Conversely, NAFLD is a predictor of other metabolic risks. NAFLD is currently the most frequent chronic liver disease but should not be considered benign or anecdotic because a considerable proportion of patients with NAFLD progress to cirrhosis and end-stage liver disease. Consequently, the search for alternative molecular mechanisms with therapeutic implications in NAFLD and associated disorders deserves a careful consideration. Mitochondria are possible targets as these organelles generate energy from nutrient oxidation. Some findings, generated in patients with extreme obesity and in murine models, support the notion that NAFLD could be a mitochondrial disease. This is plausible because mitochondrial dysfunction affects the accumulation of lipids in hepatocytes and promotes lipid peroxidation, the production of reactive oxygen species, the release of cytokines causing inflammation and cell death. Here we discuss basic research and mechanistic studies targeting the role of chemokine ligand 2 in liver inflammation and that of the paraoxonases in the oxidative stress. Their combination and association with mitochondrial dysfunction may uncover mechanisms underlying the progression of NAFLD and may help to identify novel therapeutic targets.

  5. Comparison of the Effects of Edible Oils: Rice Bran, Grape Seed, and Canola on Serum Lipid Profile and Paraoxonase Activity in Hyperlipidemic Rats

    Directory of Open Access Journals (Sweden)

    Maryam Ranjbar-Zahedani

    2015-03-01

    Full Text Available Background: Dyslipidemia is considered as one of the crucial contributors to cardio- cerebro-vascular diseases. Objectives: The present study aimed to compare the effects of Rice Barn Oil (RBO, Grape Seed Oil (GSO, and Canola Oil (CO on dyslipidemia and oxidative stress in experimentally induced hyperlipidemic rats. Materials and Methods: In the present experimental study, forty hyperlipidemic male Wistar rats were randomly assigned to 4 groups to receive RBO, GSO, or CO or Soy Bean Oil (SBO, as controls, for 4 weeks following a 3-week period of Atherogenic Diet (AD intake. Blood samples were collected at the beginning of the study, after inducing dyslipidemia, and at the end of the experimental period. Then, the data were entered into the SPSS statistical software (v. 13.0 and analyzed using paired t-test, paired sample Wilcoxon signed rank test, and Kruskal-Wallis test. Results: AD elevated lipid and/or lipoprotein profile and decreased the paraoxonase activity in the hyperlipidemic rats. The results of paired t-test revealed that RBO led to a significant improvement in serum lipoprotein profile and paraoxonase activity. Besides, a significant difference was found in the GSO group regarding all the measured parameters, except for paraoxonase activity. Moreover, CO diet showed a significant hypolipidemic effect on serum Triglyceride (TG and Total Cholesterol (TC and led to a slight improvement in Low Density Lipoprotein-Cholesterol (LDL-C and High Density Lipoprotein-Cholesterol (HDL-C. Conclusions: The results of the present study suggested that vegetable oils, including RBO, GSO, and CO, might improve dyslipidemia and oxidative stress in hyperlipidemic rats. Indeed, substituting saturated fatty acids with unsaturated fatty acids in rats’ diet had beneficial effects on serum lipid profile and oxidative stress. Comparison of the 3 edible oils showed that GSO had a more profound effect on decreasing hyperlipidemia.

  6. The relationships of leptin, adiponectin levels and paraoxonase activity with metabolic and cardiovascular risk factors in females treated with psychiatric drugs

    Directory of Open Access Journals (Sweden)

    Aliye Ozenoglu

    2008-01-01

    Full Text Available OBJECTIVES: The aim of this study was to investigate serum leptin, adiponectin and paraoxonase1 levels in adult females receiving pharmacotherapy for various psychiatric disorders. METHODS: The study group consisted of 32 obese females (mean age 40.53 ± 11.00 years, mean body mass index 35.44 ± 5.33 kg/m² who were receiving treatment for psychiatric disorders, and the control group included 22 obese females (mean age 35.95 ± 9.16 years, mean body mass index 30.78 ± 3.33 kg/m² who were free of psychiatric disorders. Analyses were performed using a bioelectrical impedance device. Fasting blood samples were obtained for complete blood count and various biochemical tests, including determination of leptin, adiponectin and paraoxonase1 activity. RESULTS: Body mass index, waist and hip circumference, body fat percentage, fasting blood glucose, insulin, glycosylated hemoglobin, homeostasis model assesment of insulin resistance, alanine transaminase, aspartate tarnsaminase, and leptin levels were significantly higher in the study group than in controls. Although body weight was positively correlated with leptin levels in both groups, body weight was negatively correlated with adiponectin levels in the control group and positively correlated with adiponectin levels in the study group. In the study group, body mass index and hip circumference correlated positively with leptin levels, hip circumference correlated positively with adiponectin levels, and waist to hip ratio correlated positively with paraoxonase levels. In the control group, body mass index as well as waist and hip circumferences were positively correlated with leptin levels. Weight, body mass index, and hip circumference were also negatively correlated with the adiponectin/leptin ratio in the control group. CONCLUSION: This study indicates a higher risk for obesity-related disorders, particularly metabolic syndrome, diabetes and cardiovascular disease, in patients treated with

  7. Ascorbic acid partly antagonizes resveratrol mediated heme oxygenase-1 but not paraoxonase-1 induction in cultured hepatocytes - role of the redox-regulated transcription factor Nrf2

    OpenAIRE

    Hori Osamu; Hashida Koji; Döring Frank; Schmelzer Constance; Schrader Charlotte; Breckwoldt Dorothea; Boesch-Saadatmandi Christine; Wagner Anika E; Matsugo Seiichi; Rimbach Gerald

    2011-01-01

    Abstract Background Both resveratrol and vitamin C (ascorbic acid) are frequently used in complementary and alternative medicine. However, little is known about the underlying mechanisms for potential health benefits of resveratrol and its interactions with ascorbic acid. Methods The antioxidant enzymes heme oxygenase-1 and paraoxonase-1 were analysed for their mRNA and protein levels in HUH7 liver cells treated with 10 and 25 μmol/l resveratrol in the absence and presence of 100 and 1000 μmo...

  8. Combined Effects of Curcumin and Lycopene or Bixin in Yoghurt on Inhibition of LDL Oxidation and Increases in HDL and Paraoxonase Levels in Streptozotocin-Diabetic Rats

    Science.gov (United States)

    Assis, Renata Pires; Arcaro, Carlos Alberto; Gutierres, Vânia Ortega; Oliveira, Juliana Oriel; Costa, Paulo Inácio; Baviera, Amanda Martins; Brunetti, Iguatemy Lourenço

    2017-01-01

    Combination therapy using natural antioxidants to manage diabetes mellitus and its complications is an emerging trend. The aim of this study was to investigate the changes promoted by treatment of streptozotocin (STZ)-diabetic rats with yoghurt enriched with the bioactives curcumin, lycopene, or bixin (the latter two being carotenoids). Antioxidants were administered individually, or as mixtures, and biomarkers of metabolic and oxidative disturbances, particularly those associated with cardiovascular risk, were assessed. Treatment of STZ-diabetic rats with natural products individually decreased glycemia, triacylglycerol, total-cholesterol, oxidative stress biomarkers, including oxidized low-density lipoprotein (ox-LDL), and increased the activities of antioxidant enzymes. Individual carotenoids increased both high-density lipoprotein (HDL) and paraoxonase levels, whereas curcumin increased only paraoxonase. Treatments with mixtures of curcumin and lycopene or bixin had combined effects, decreasing biomarkers of carbohydrate and lipid disturbances (curcumin effect), increasing the HDL levels (carotenoids effects) and mitigating oxidative stress (curcumin and carotenoids effects). The combined effects also led to prevention of the LDL oxidation, thereby mitigating the cardiovascular risk in diabetes. These findings provide evidence for the beneficial effect of curcumin and carotenoid mixtures as a supplementation having antioxidant and antiatherogenic potentials, thus appearing as an interesting strategy to be studied as a complementary therapy for diabetic complications. PMID:28333071

  9. Combined Effects of Curcumin and Lycopene or Bixin in Yoghurt on Inhibition of LDL Oxidation and Increases in HDL and Paraoxonase Levels in Streptozotocin-Diabetic Rats.

    Science.gov (United States)

    Assis, Renata Pires; Arcaro, Carlos Alberto; Gutierres, Vânia Ortega; Oliveira, Juliana Oriel; Costa, Paulo Inácio; Baviera, Amanda Martins; Brunetti, Iguatemy Lourenço

    2017-03-23

    Combination therapy using natural antioxidants to manage diabetes mellitus and its complications is an emerging trend. The aim of this study was to investigate the changes promoted by treatment of streptozotocin (STZ)-diabetic rats with yoghurt enriched with the bioactives curcumin, lycopene, or bixin (the latter two being carotenoids). Antioxidants were administered individually, or as mixtures, and biomarkers of metabolic and oxidative disturbances, particularly those associated with cardiovascular risk, were assessed. Treatment of STZ-diabetic rats with natural products individually decreased glycemia, triacylglycerol, total-cholesterol, oxidative stress biomarkers, including oxidized low-density lipoprotein (ox-LDL), and increased the activities of antioxidant enzymes. Individual carotenoids increased both high-density lipoprotein (HDL) and paraoxonase levels, whereas curcumin increased only paraoxonase. Treatments with mixtures of curcumin and lycopene or bixin had combined effects, decreasing biomarkers of carbohydrate and lipid disturbances (curcumin effect), increasing the HDL levels (carotenoids effects) and mitigating oxidative stress (curcumin and carotenoids effects). The combined effects also led to prevention of the LDL oxidation, thereby mitigating the cardiovascular risk in diabetes. These findings provide evidence for the beneficial effect of curcumin and carotenoid mixtures as a supplementation having antioxidant and antiatherogenic potentials, thus appearing as an interesting strategy to be studied as a complementary therapy for diabetic complications.

  10. Paraoxonase 3 Activity and The Ratio of Antioxidant to Peroxidation in The Follicular Fluid of Infertile Women

    Directory of Open Access Journals (Sweden)

    Mohammad-Reza Rashidi

    2014-03-01

    Full Text Available Background: Paraoxonase-3 (PON3, as a high density lipoprotein (HDL-associated lactonase, is capable of preventing the oxidative modification of low density lipoprotein (LDL. PON3 activity in follicular fluid (FF is three times more than its activity in serum. However, the detailed role of PON3 in women’s fertility remains unknown. The aim of this study was to investigate the correlation between PON3 activity in the FF of women undergoing assisted reproductive technique (ART, in vitro fertilization (IVF, or intra-cytoplasmic sperm injection (ICSI. Materials and Methods: This cross-sectional study consisted of 50 women from couples with male factor infertility (MFI or with female factor infertility (FFI. The FF samples were obtained during the ART intervention. PON3 activity, HDL cholesterol (HDL C, total antioxidant status (TAS and the level of malondialdehyde (MDA were determined. The morphology of the embryo was determined using embryo cell number (ECN and embryo fragmentation score (EFS. In addition, fertilization rate (FR was used an oocyte fertilization index. Results: Of 50 women, 20 women belonged to FFI group and the remaining 30 women belonged to MFI group. PON3 activity in FF of women in FFI group was significantly lower (p<0.05 in comparison with corresponding value in MFI group. The value of PON3 activity/MDA in the FFI group was lower than that in MFI group. Moreover, MDA level in the FF of FFI group was significantly higher (p<0.05 than its concentration in MFI group. Meanwhile, no significant difference was found in HDL-C concentration and TAS of both groups. No significant correlation was observed between the ECN and FF biochemical parameters. There was also a negative correlation between FR and MDA (r=-0.42, p=0.02, whereas a positive relation between FR with PON3 activity (r=0.59, p=0.004, HDL-C (r=0.35, p=0.04 and PON3/MDA (r=0.59, p=0.001. Conclusion: According to the results of this study, PON3 activity level as a key

  11. Elevated HDL2-paraoxonase and reduced CETP activity are associated with a dramatically lower ratio of LDL-cholesterol/total cholesterol in a hypercholesterolemic and hypertriglyceridemic patient.

    Science.gov (United States)

    Lee, Ji-Hye; Park, Jung-Heun; Lee, Sang-Hak; Kim, Jae-Ryong; Cho, Kyung-Hyun

    2010-06-01

    A female patient (64 years of age; body mass index, 26) had a markedly and relatively low low-density lipoprotein-cholesterol (LDL-C) level (97 mg/dl) despite high serum total cholesterol (TC) (331 mg/dl) and triacylglyceride levels (307 mg/dl). Since the expected LDL-C was 222 mg/dl, there was a significant difference between the calculation and measurement based on direct enzyme assay. Only 30% of serum cholesterol was associated with LDL-C in this patient. To determine the basis for the markedly low LDL-C/TC ratio, we isolated and analyzed lipoproteins from the patient as well as age- and gender-matched controls. The patient had lowered serum CETP activity and elevated paraoxonase activity with GOT and GPT values in the normal range. The very low-density lipoprotein particles from the patient were larger than those of the controls and enriched with lipid and protein, while the LDL from the patient (LDL-P) had a lower particle number and protein content than the controls. The LDL-P was more resistant to cupric ion-mediated oxidation. HDL2 from the patient (HDL2-P) had highly enhanced paraoxonase activity and antioxidant ability. The patient had a 1.5-fold higher level of apolipoprotein (apo) A-I expression in HDL2. ApoA-I in HDL2 and HDL3 from the patient showed no fragmentation, while the control had fragmented bands (17 and 21 kDa) in the HDL. The HDL2-P also had a larger particle size and greater protein content with less lipid content. HDL3-associated cholesteryl ester transfer protein was reduced in the patient, although the particle size was similar to the controls. In conclusion, a patient who had a markedly lower LDL-C/TC ratio despite hyperlipidemia associated with higher paraoxonase activity, higher apoA-I level and lower CETP activity without fragmentation of apoA-I in the HDL fraction is presented. The enhanced antioxidant and anti-inflammatory activity of HDL might contribute to the low LDL-C/TC ratio in this patient.

  12. Effect of virgin coconut oil enriched diet on the antioxidant status and paraoxonase 1 activity in ameliorating the oxidative stress in rats - a comparative study.

    Science.gov (United States)

    Arunima, S; Rajamohan, T

    2013-09-01

    Virgin coconut oil (VCO) extracted by wet processing is popular among the scientific field and society nowadays. The present study was carried out to examine the comparative effect of VCO with copra oil (CO), olive oil (OO) and sunflower oil (SFO) on endogenous antioxidant status and paraoxonase 1 activity in ameliorating the oxidative stress in rats. Male Sprague-Dawley rats were fed different oils at 8% level for 45 days along with the synthetic diet. Results revealed that dietary VCO improved the antioxidant status compared to other three oil fed groups (P oil fed groups (P oil fed rats (P oil) and tocopherols (33.12 μg per 100 g oil) etc. compared to other oils (P < 0.05). From these observations, it is concluded that VCO has a beneficial role in improving antioxidant status and hence preventing lipid and protein oxidation.

  13. Chimeric proteins combining phosphatase and cellulose-binding activities: proof-of-concept and application in the hydrolysis of paraoxon.

    Science.gov (United States)

    Gonçalves, Larissa M; Chaimovich, Hernan; Cuccovia, Iolanda M; Marana, Sandro R

    2014-05-01

    Phosphatases for organophosphate degradation and carbohydrate-binding domains (CBMs) have potential biotechnological applications. As a proof-of-concept, a soluble chimeric protein that combines acid phosphatase (AppA) from Escherichia coli and a CBM from Xanthomonas axonopodis pv. citri (AppA-CBM) was produced in E.coli. AppACBM adsorbed in microcrystalline cellulose Avicel PH101 catalyzed the hydrolysis of p-nitrophenyl phosphate (PNPP). The binding to microcrystalline cellulose displayed saturation behavior with an apparent binding constant (Kb) of 22 ± 5 mg and a maximum binding (Bmax) of 1.500 ± 0.001 enzyme units. Binding was highest at pH 2.5 and decreased above pH 6.5, as previously observed for family 2 CBMs. The Km values for PNPP of AppA-CBM and native AppA were identical (2.7 mM). To demonstrate that this strategy for protein engineering has practical applications and is largely functional, even for phosphatases exhibiting diverse folds, a chimeric protein combining human paraoxonase 1 (hPON1) and the CBM was produced. Both PON1-CBM and hPON1 had identical Km values for paraoxon (1.3 mM). Additionally, hPON1 bound to microcrystalline cellulose with a Kb of 27 ± 3 mg, the same as that observed for AppA-CBM. These data show that the phosphatase domains are as functional in both of the chimeric proteins as they are in the native enzymes and that the CBM domain maintains the same cellulose affinity. Therefore, the engineering of chimeric proteins combining domains of phosphatases and CBMs is fully feasible, resulting in chimeric enzymes that exhibit potential for OP detoxification.

  14. Paraoxonases-2 and -3 Are Important Defense Enzymes against Pseudomonas aeruginosa Virulence Factors due to Their Anti-Oxidative and Anti-Inflammatory Properties

    Directory of Open Access Journals (Sweden)

    Eva-Maria Schweikert

    2012-01-01

    Full Text Available The pathogen Pseudomonas aeruginosa causes serious damage in immunocompromised patients by secretion of various virulence factors, among them the quorum sensing N-(3-oxododecanoyl-L-homoserine lactone (3OC12 and the redox-active pyocyanin (PCN. Paraoxonase-2 (PON2 may protect against P. aeruginosa infections, as it efficiently inactivates 3OC12 and diminishes PCN-induced oxidative stress. This defense could be circumvented because 3OC12 mediates intracellular Ca2+-rise in host cells, which causes rapid inactivation and degradation of PON2. Importantly, we recently found that the PON2 paralogue PON3 prevents mitochondrial radical formation. Here we investigated its role as additional potential defense mechanism against P. aeruginosa infections. Our studies demonstrate that PON3 diminished PCN-induced oxidative stress. Moreover, it showed clear anti-inflammatory potential by protecting against NF-κB activation and IL-8 release. The latter similarly applied to PON2. Furthermore, we observed a Ca2+-mediated inactivation and degradation of PON3, again in accordance with previous findings for PON2. Our results suggest that the anti-oxidative and anti-inflammatory functions of PON2 and PON3 are an important part of our innate defense system against P. aeruginosa infections. Furthermore, we conclude that P. aeruginosa circumvents PON3 protection by the same pathway as for PON2. This may help identifying underlying mechanisms in order to sustain the protection afforded by these enzymes.

  15. A Simple,Stable,Reliable Method for Analysis of Paraoxonase 1 Gene Polymorphism%一种简单、稳定、可靠的屏氧酶1基因多态性分析法

    Institute of Scientific and Technical Information of China (English)

    胡春松; Yu-JingZhao; 等

    2002-01-01

    目的:建立一种简单、稳定、可靠的PON1基因多态性分析法.方法:取外周静脉血100 μl,用ROSE法提取基因组DNA,用两对引物:P192F 5'-TAT TGT TGC TGT GGG ACC TGA G-3',P192R 5'-CAC GCT AAA CCC AAA TAC ATC TC-3';P55F 5'-GAA GAG TGA TGT ATA GCC CCA G-3',P55R 5'-TTT AAT CCA GAG CTA ATG AAA GCC-3'分别进行PCR扩增,用限制性内切酶AlwI,NlaⅢ对两种PCR产物分别进行酶切,3%琼脂糖凝胶电脉.结果:扩增的两个PCR产物在192、55多态性位点大小分别为99bp、170bp.AlwⅠ酶切后,凝胶电脉得到完全酶切(66bp,33bp), 部分酶切(99bp、66bp、33bp),未被酶切(99bp)三种类型DNA片段(RR, QR, QQ基因型) ;NlaⅢ酶切后,凝胶电脉得到部分酶切(170bp,126bp,44bp), 未被酶切(170bp)两种类型DNA片段(LM,LL基因型).经双盲重复检测,结果一致.应用此方法对胃癌患者血样标本检测,发现其PON1基因多态性在192位点频率较高.结论:采用一步PCR-RFLP技术可以建立简单、稳定、可靠的PON1基因多态性分析法.

  16. Nitro-Oleic Acid Reduces J774A.1 Macrophage Oxidative Status and Triglyceride Mass: Involvement of Paraoxonase2 and Triglyceride Metabolizing Enzymes.

    Science.gov (United States)

    Rosenblat, Mira; Rom, Oren; Volkova, Nina; Aviram, Michael

    2016-08-01

    Nitro-fatty acids possess anti-atherogenic properties, but their effects on macrophage oxidative status and lipid metabolism that play important roles in atherosclerosis development are unclear. This study compared the effects of nitro-oleic acid (OLA-NO2) with those of native oleic acid (OLA) on intracellular reactive oxygen species (ROS) generation, anti-oxidants and metabolism of triglycerides and cholesterol in J774A.1 macrophages. Upon incubating the cells with physiological concentrations of OLA-NO2 (0-1 µM) or with equivalent levels of OLA, ROS levels measured by 2, 7-dichlorofluorescein diacetate, decreased dose-dependently, but the anti-oxidative effects of OLA-NO2 were significantly augmented. Copper ion addition increased ROS generation in OLA treated macrophages without affecting OLA-NO2 treated cells. These effects could be attributed to elevated glutathione levels and to increased activity and expression of paraoxonase2 that were observed in OLA-NO2 vs OLA treated cells. Beneficial effects on triglyceride metabolism were noted in OLA-NO2 vs OLA treated macrophages in which cellular triglycerides were reduced due to attenuated biosynthesis and accelerated hydrolysis of triglycerides. Accordingly, OLA-NO2 treated cells demonstrated down-regulation of diacylglycerol acyltransferase1, the key enzyme in triglyceride biosynthesis, and increased expression of hormone-sensitive lipase and adipose triglyceride lipase that regulate triglyceride hydrolysis. Finally, OLA-NO2 vs OLA treatment resulted in modest but significant beneficial effects on macrophage cholesterol metabolism, reducing cholesterol biosynthesis rate and low density lipoprotein influx into the cells, while increasing high density lipoprotein-mediated cholesterol efflux from the macrophages. Collectively, compared with OLA, OLA-NO2 modestly but significantly reduces macrophage oxidative status and cellular triglyceride content via modulation of cellular anti-oxidants and triglyceride

  17. Paraoxonase 2 modulates a proapoptotic function in LS174T cells in response to quorum sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone.

    Science.gov (United States)

    Tao, Shiyu; Luo, Yanwen; Bin He; Liu, Jie; Qian, Xi; Ni, Yingdong; Zhao, Ruqian

    2016-07-01

    A mucus layer coats the gastrointestinal tract and serves as the first line of intestinal defense against infection. N-acyl-homoserine lactone (AHL) quorum-sensing molecules produced by gram-negative bacteria in the gut can influence the homeostasis of intestinal epithelium. In this study, we investigated the effects of two representative long- and short-chain AHLs, N-3-(oxododecanoyl)-homoserine lactone (C12-HSL) and N-butyryl homoserine lactone (C4-HSL), on cell viability and mucus secretion in LS174T cells. C12-HSL but not C4-HSL significantly decreased cell viability by inducing mitochondrial dysfunction and activating cell apoptosis which led to a decrease in mucin expression. Pretreatment with lipid raft disruptor (Methyl-β-cyclodextrin, MβCD) and oxidative stress inhibitor (N-acetyl-L-cysteine, NAC) slightly rescued the viability of cells damaged by C12-HSL exposure, while the paraoxonase 2 (PON2) inhibitor (Triazolo[4,3-a]quinolone, TQ416) significantly affected recovering cells viability and mucin secretion. When LS174T cells were treated with C12-HSL and TQ416 simultaneously, TQ416 showed the maximal positive effect on cells viability. However, if cells were first treated with C12-HSL for 40 mins, and then TQ46 was added, the TQ416 had no effect on cell viability. These results suggest that the C12-HSL-acid process acts at an early step to activate apoptosis as part of C12-HSL's effect on intestinal mucus barrier function.

  18. Serum biomarkers of oxidative stress in cats with feline infectious peritonitis.

    Science.gov (United States)

    Tecles, F; Caldín, M; Tvarijonaviciute, A; Escribano, D; Martínez-Subiela, S; Cerón, J J

    2015-06-01

    The purpose of this study was to elucidate the possible presence of oxidative stress in cats naturally affected by feline infectious peritonitis (FIP) by investigating two antioxidant biomarkers in serum: paraoxonase-1 (PON1) and total antioxidant capacity (TAC). PON1 was measured by spectrophotometric assays using three different substrates: p-nitrophenyl acetate (pNA), phenyl acetate (PA) and 5-thiobutil butyrolactone (TBBL), in order to evaluate possible differences between them. The PA and TBBL assays for PON1 and the assay for TAC were validated, providing acceptable precision and linearity although PA and TAC assays showed limit of detection higher than the values found in some cats with FIP. Cats with FIP and other inflammatory conditions showed lower PON1 values compared with a group of healthy cats with the three assays used, and cats with FIP showed significant decreased TAC concentrations. This study demonstrated the existence of oxidative stress in cats with FIP.

  19. The role of genetic variants in human longevity.

    Science.gov (United States)

    Chung, Wen-Hung; Dao, Ro-Lan; Chen, Liang-Kung; Hung, Shuen-Iu

    2010-11-01

    Human longevity is a complex phenotype with a strong genetic predisposition. Increasing evidence has revealed the genetic antecedents of human longevity. This article aims to review the data of various case/control association studies that examine the difference in genetic polymorphisms between long-lived people and younger subjects across different human populations. There are more than 100 candidate genes potentially involved in human longevity; this article particularly focuses on genes of the insulin/IGF-1 pathway, FOXO3A, FOXO1A, lipoprotein metabolism (e.g., APOE and PON1), and cell-cycle regulators (e.g., TP53 and P21). Since the confirmed genetic components for human longevity are few to date, further precise assessment of the genetic contributions is required. Gaining a better understanding of the contribution of genetics to human longevity may assist in the design of improved treatment methods for age-related diseases, delay the aging process, and, ultimately, prolong the human lifespan.

  20. Altered lipid peroxidation markers are related to post-traumatic stress disorder (PTSD) and not trauma itself in earthquake survivors.

    Science.gov (United States)

    Atli, Abdullah; Bulut, Mahmut; Bez, Yasin; Kaplan, İbrahim; Özdemir, Pınar Güzel; Uysal, Cem; Selçuk, Hilal; Sir, Aytekin

    2016-06-01

    The traumatic life events, including earthquakes, war, and interpersonal conflicts, cause a cascade of psychological and biological changes known as post-traumatic stress disorder (PTSD). Malondialdehyde (MDA) is a reliable marker of lipid peroxidation, and paraoxonase is a known antioxidant enzyme. The aims of this study were to investigate the relationship between earthquake trauma, PTSD effects on oxidative stress and the levels of serum paraoxonase 1 (PON1) enzyme activity, and levels of serum MDA. The study was carried out on three groups called: the PTSD group, the traumatized with earthquake exercise group, and healthy control group, which contained 32, 31, and 38 individuals, respectively. Serum MDA levels and PON1 enzyme activities from all participants were measured, and the results were compared across all groups. There were no significant differences between the PTSD patients and non-PTSD earthquake survivors in terms of the study variables. The mean PON1 enzyme activity from PTSD patients was significantly lower, while the mean MDA level was significantly higher than that of the healthy control group (p earthquake survivors who did not develop PTSD showed higher MDA levels and lower PON1 activity when compared to healthy controls. However, the differences between these groups did not reach a statistically significant level. Increased MDA level and decreased PON1 activity measured in PTSD patients after earthquake and may suggest increased oxidative stress in these patients. The nonsignificant trends that are observed in lipid peroxidation markers of earthquake survivors may indicate higher impact of PTSD development on these markers than trauma itself. For example, PTSD diagnosis seems to add to the effect of trauma on serum MDA levels and PON1 enzyme activity. Thus, serum MDA levels and PON1 enzyme activity may serve as biochemical markers of PTSD diagnosis.

  1. A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human.

    Directory of Open Access Journals (Sweden)

    Ulkan Kilic

    Full Text Available Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene.

  2. A Remarkable Age-Related Increase in SIRT1 Protein Expression against Oxidative Stress in Elderly: SIRT1 Gene Variants and Longevity in Human

    Science.gov (United States)

    Kilic, Ulkan; Gok, Ozlem; Erenberk, Ufuk; Dundaroz, Mehmet Rusen; Torun, Emel; Kucukardali, Yasar; Elibol-Can, Birsen; Uysal, Omer; Dundar, Tolga

    2015-01-01

    Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene. PMID:25785999

  3. Gene expression and functional annotation of the human and mouse choroid plexus epithelium.

    Directory of Open Access Journals (Sweden)

    Sarah F Janssen

    Full Text Available BACKGROUND: The choroid plexus epithelium (CPE is a lobed neuro-epithelial structure that forms the outer blood-brain barrier. The CPE protrudes into the brain ventricles and produces the cerebrospinal fluid (CSF, which is crucial for brain homeostasis. Malfunction of the CPE is possibly implicated in disorders like Alzheimer disease, hydrocephalus or glaucoma. To study human genetic diseases and potential new therapies, mouse models are widely used. This requires a detailed knowledge of similarities and differences in gene expression and functional annotation between the species. The aim of this study is to analyze and compare gene expression and functional annotation of healthy human and mouse CPE. METHODS: We performed 44k Agilent microarray hybridizations with RNA derived from laser dissected healthy human and mouse CPE cells. We functionally annotated and compared the gene expression data of human and mouse CPE using the knowledge database Ingenuity. We searched for common and species specific gene expression patterns and function between human and mouse CPE. We also made a comparison with previously published CPE human and mouse gene expression data. RESULTS: Overall, the human and mouse CPE transcriptomes are very similar. Their major functionalities included epithelial junctions, transport, energy production, neuro-endocrine signaling, as well as immunological, neurological and hematological functions and disorders. The mouse CPE presented two additional functions not found in the human CPE: carbohydrate metabolism and a more extensive list of (neural developmental functions. We found three genes specifically expressed in the mouse CPE compared to human CPE, being ACE, PON1 and TRIM3 and no human specifically expressed CPE genes compared to mouse CPE. CONCLUSION: Human and mouse CPE transcriptomes are very similar, and display many common functionalities. Nonetheless, we also identified a few genes and pathways which suggest that the CPE

  4. The usefulness of advanced lipid and oxidative stress testing for diagnosis and management of low HDL-cholesterol phenotype: A case report.

    Science.gov (United States)

    Kuburovic, Vladimir; Vekic, Jelena; Zeljkovic, Aleksandra; Carrie, Alain; Kotur-Stevuljevic, Jelena; Bojanin, Dragana; Kosutic, Jovan; Spasojevic-Kalimanovska, Vesna; Miljkovic, Milica; Kuburovic, Nina; Couvert, Philippe

    2017-06-23

    Plasma high-density lipoprotein cholesterol (HDL-C) level is a strong inverse predictor of cardiovascular disease (CVD) development. Tangier disease, a consequence of mutations in the ATP binding cassette transporter 1 (ABCA1) gene, is associated with very low HDL-C levels. Still, the relationship between Tangier disease and CVD is not always evident. The study investigates usefulness of lipoprotein subfractions, oxidative stress and paraoxonase 1 (PON1) status assessment for evaluation and management of patient with low HDL-C phenotype. A 12-year-old boy was hospitalised due to hypertension. Laboratory evaluation revealed low HDL-C level, and subsequent molecular diagnostic confirmed Tangier disease. Lipoprotein subfractions were assessed by gradient-gel electrophoresis. Oxidative stress status was estimated by measuring total antioxidative status, total oxidative status, prooxidative-antioxidative balance, malondialdehyde and advanced oxidation protein products levels. Activity of paraoxonase 1 in serum and its distribution within HDL subclasses was also determined (ten healthy boys aged 13.1±3.4years served as the reference group). Analysis of oxidative stress status biomarkers revealed a state of prolonged prooxidants activity. In turn, serum PON1 activity was substantially reduced. The majority of PON1 activity was present on HDL 2 particles. Impaired antioxidative potential of HDL may point toward hidden cardiovascular risk in isolated low HDL-phenotype. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  5. Organophosphorous pesticides research in Mexico: epidemiological and experimental approaches.

    Science.gov (United States)

    Sánchez-Guerra, M; Pérez-Herrera, N; Quintanilla-Vega, B

    2011-11-01

    Non-persistent pesticides, such as organophosphorous (OP) insecticides have been extensively used in Mexico, and becoming a public health problem. This review presents data of OP use and related toxicity from epidemiological and experimental studies conducted in Mexico. Studies in agricultural workers from several regions of the country reported moderate to severe cholinergic symptoms, including decreased acetylcholinesterase (AChE) activity (the main acute OP toxic effect that causes an over accumulation of the neurotransmitter acetylcholine), revealing the potential risk of intoxication of Mexican farmers. OP exposure in occupational settings has been associated with decreased semen quality, sperm DNA damage and as endocrine disrupter, particularly in agricultural workers. Alterations in female reproductive function have also been observed, as well as adverse effects on embryo development by prenatal exposure in agricultural communities. This illustrates that OP exposure represents a risk for reproduction and offspring well-being in Mexico. The genotoxic effects of this group of pesticides in somatic and sperm cells are also documented. Lastly, we present data about gene-environmental interactions regarding OP metabolizing enzymes, such as paraoxonase-1 (PON1) and its role in modulating their toxicity, particularly on semen quality and sperm DNA integrity. In summary, readers will see the important health problems associated with OP exposure in Mexican populations, thereby the need of capacitation programs to communicate farmers the proper handling of agrochemicals to prevent their toxic effects and of more well designed human studies to support data of the current situation of workers and communities dedicated to agriculture activities.

  6. Esterase detoxification of acetylcholinesterase inhibitors by human or rat liver in vitro

    Science.gov (United States)

    Organophosphate (OP) and N-methylcarbamate pesticides inhibit acetylcholinesterase (AChE), but differences in metabolism and detoxification can influence potency of these pesticides across and within species. Carboxylesterase (CaE) and A-esterase (paraoxonase, PON) are considered...

  7. Influence of heredity on human sensitivity to environmental chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Weber, W.W. [Univ. of Michigan, Ann Arbor, MI (United States)

    1995-12-31

    Hereditary peculiarities in individual responses to environmental chemicals are a common occurrence in human populations. Genetic variation in glutathione S-transferase, CYP1A2, N-acetyltransferase, and paraoxonase exemplify the relationship of metabolic variation to individual susceptibility to cancer and other toxicants of environmental origin. Heritable receptor protein variants, a subset of proteins of enormous pharmacogenetic, potential that have not thus far been extensively explored form the pharmacogenetic standpoint, and also considered. Examples of interest that are considered include receptor variants associated with retinoic acid resistance in acute promyelocytic leukemia, with paradoxical responses to antiandrogens in prostate cancer, and with retinitis pigmentosa. Additional heritable protein variants of pharmacogenetic interest that result in antibiotic-induced deafness, glucocorticoid-remediable aldosteronism and hypertension, the long-QT syndrome, and beryllium-induced lung disease are also discussed. These traits demonstrate how knowledge of the molecular basis and mechanism of the variant response may contribute to its prevention in sensitive persons as well as to improved therapy for genetically conditioned disorders that arise form environmental chemicals. 99 refs.

  8. Lipid mobilisation and oxidative stress as metabolic adaptation processes in dairy heifers during transition period.

    Science.gov (United States)

    Turk, R; Podpečan, O; Mrkun, J; Kosec, M; Flegar-Meštrić, Z; Perkov, S; Starič, J; Robić, M; Belić, M; Zrimšek, P

    2013-10-01

    The objective of this study was to evaluate metabolic disorders and oxidative stress in dairy heifers during the transition period. Possible relationships between lipid mobilisation indicators and oxidative stress markers were investigated as well. Nineteen dairy heifers were included in the study. Blood samples were collected at the time of estrus synchronisation in heifers, at insemination, three weeks after insemination, one week before calving, at calving and 1, 2, 4 and 8 weeks postpartum. Common metabolic parameters, beta-hydroxybutyrate (BHB), free fatty acids (FFA), paraoxonase-1 (PON1) activity and total antioxidative status (TAS) were analysed. Around insemination, no significant difference was observed in the majority of tested parameters (P>0.05). However, the transition period markedly affected the concentration of triglycerides, total cholesterol, HDL-C, BHB, FFA, TAS and PON1activity. Positive correlations between PON1 activity and total cholesterol, HDL-C and triglycerides were noted but inverse correlations with FFA, BHB and bilirubin were found indicating that PON1 activity changed with lipid metabolism and was influenced by negative energy balance. These findings suggest that lipid mobilisation and oxidative stress are part of a complex metabolic adaptation to low energy balance which reaches equilibrium later in advanced lactation.

  9. Relación entre paraoxonasa, otros componentes de HDL y estado inflamatorio en hemodiálisis Relation between paraoxonase activity, other HDL components and inflammatory conditions in hemodialyzed patients

    Directory of Open Access Journals (Sweden)

    Ana Inés González

    2010-12-01

    -rich lipoproteins and decrease in HDL level. HDL contains antioxidant enzymes such as paraoxonase (PON, whose activity is diminished in CKD. The aim of our study was to evaluate the relationship between PON activity with HDL cholesterol, apo A1 and hs-CRP levels, which are known to be inflammatory markers in hemodialyzed patients. Forty-two patients were studied; age, median (range = 50 (25-67 years old, gender M/F = 22/20, duration of hemodialysis = 4.4 ± 0.5 years, BMI: 23 ± 0.5 kg/m². After a 12 h fast, a blood sample was obtained and classic components of lipid profile were determined, as well as apoproteins A1 and B, PON by means of its arylsterase activity and hs-CRP levels. On the basis of the latter, patients were divided into two groups: hs-CRP ≤ 1 (low risk, range: 0.1 to 1.0 mg/l and >1 mg/l (moderate and high risk, 1.1 to 10.7 mg/l. No difference was found in triglycerides, LDL cholesterol and apo B in the groups. Patients with hs-CRP > 1 showed lower HDL cholesterol (40 ± 2 mg/dl and apo A1 (118 ± 4 mg/dl than patients with hs-CRP ≤ 1 (50 ± 4 and 133 ± 5, respectively; p 1 = 90.5 ± 24.0 μmol/ml.min than in hs-CRP ≤ 1 = 105.2 ± 18.0. Consequently, inverse correlations were obtained between apo A1 and hs-CRP, r = -0.381, p = 0.013 and between PON and hs-CRP, r = -0.32, p = 0.042. Furthermore, increase in hs-CRP correlated positively with BMI r = 0.318, p = 0.042. Since apo A1 has an anti-inflammatory role and PON an antioxidant activity, the decrease in HDL and its components, cholesterol, apo A1 and PON, in subjects with higher chronic inflammatory condition might explain, in part, the increased cardiovascular risk in these patients.

  10. Comparison of serum oxidant and antioxidant parameters in familial Mediterranean fever patients (FMF) with attack free period.

    Science.gov (United States)

    Şahin, Ali; Erten, Şükran; Altunoğlu, Alpaslan; Işıkoğlu, Semra; Neşelioğlu, Salim; Ergin, Merve; Atalay, Hacı Veli; Erel, Özcan

    2014-01-01

    Familial Mediterranean fever (FMF) is an autoinflammatory, autosomal recessive, inherited disease characterized by recurrent self-limiting attacks of serosal surfaces. The imbalance of oxidants/antioxidants may play a role in such attacks. In this study, we aimed to evaluate the relationship between serum paraoxonase (PON1) activity, PON1 phenotype, and other parameters in patients with FMF and healthy controls. A total of 120 FMF patients with an attack-free period (AFP) and 65 healthy subjects were included in this study. The serum PON1 activity, stimulated paraoxonase (SPON) activity, PON1 phenotype (representing Q192R polymorphism; QQ, QR, RR), arylesterase activity, total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), advanced oxidative protein products (AOPP), total thiols (TTL), and ischemia-modified albumin (IMA) and cystatin-c (CYS-C) levels were measured. For the QQ phenotype, the median TTL and AOPP levels of the control group were 264.50 (57.75) mol/L and 21.26 (21.17) mmol/L, respectively, whereas the median TTL, AOPP levels of the patients were 309.00 (47.00) mol/L and 12.98 (6.96) mmol/L, respectively. There was a statistically significant difference between the patients and controls with the QQ phenotype in terms of TTL and AOPP (pFMF patients with AFP had higher TTL and lower AOPP levels than the controls. However, other oxidant and antioxidant parameters were similar among the patients during AFP and the controls.

  11. 血清对氧磷酯酶1联合氧化指标检测在急性有机磷中毒的临床意义%Clinical Significance of Measurement of Serum Paraoxonase 1 and Antioxidative Enzymes Levels in Patients with Acute Organophosphorus Pesticide Poisoning

    Institute of Scientific and Technical Information of China (English)

    张娟文; 吕国才; 徐根云; 金玉琴

    2008-01-01

    目的 探讨抗氧化酶及氧化应激压力在急性有机磷农药中毒(AOPP)中的意义.方法 检测28例AOPP患者血清对氧磷酯酶1(PONI)、超氧化物歧化酶(SOD)和丙二醛(MDA)的水平并与36例健康对照组比较.结果 28例AOPP患者PON1(58.9±6.4 U/ml)和SOD(82.34±9.2 U/ml)明显低于对照组PONl(140.1±8.9 U/ml)和SOD(125.5±10.9 U/ml)(P<0.01).MDA的水平(6.65 ±1.13.nmol/ml)明显高于健康对照组(2.31±0.56.nmol/ml)(P<0.01).中毒组PONI和MDA相关性分析后发现,PONI活性与MDA含量存在明显的负相关(r=-0.821,P<0.01).结论 PONI等抗氧化酶活性下降,脂质发生过氧化反应,引发的氧化应激损伤在急性有机磷农药中毒病理生理机制中发挥重要作用.

  12. Lipid profile and serum characteristics of the blind subterranean mole rat, Spalax.

    Directory of Open Access Journals (Sweden)

    Nicola J Nasser

    Full Text Available BACKGROUND: Spalax (blind subterranean mole rat, is a mammal adapted to live in fluctuating oxygen levels, and can survive severe hypoxia and hypercapnia. The adaptive evolution of Spalax to underground life resulted in structural and molecular-genetic differences comparing to above-ground mammals. These differences include higher myocardial maximal oxygen consumption, increased lung diffusion capacity, increased blood vessels density, and unique expression patterns of cancer and angiogenesis related genes such as heparanase, vascular endothelial growth factor, and P53. METHODOLOGY/PRINCIPAL FINDINGS: Here we elucidate the main characteristics of Spalax lipid profile, as well as its main antioxidant and serum parameters. Compared to human, Spalax possesses lower total-cholesterol, low density lipoproteins (LDL and triglycerides levels, and higher levels of high density lipoproteins (HDL. Apolipoprotein A-I and apolipoprotein B-100 were significantly lower in Spalax compared to human. Paraoxonase (PON 1 arylesterase activity, was higher in Spalax compared to both human and mouse serum levels. Analysis of serum chemistry of Spalax revealed special features in this mammal. CONCLUSIONS/SIGNIFICANCE: Spalax possesses a unique lipid profile with high HDL and low LDL lipoproteins. The antioxidant serum content in the mole rat is higher than that of human and mouse. Serum C reactive protein (CRP levels are significantly lower in Spalax compared to that of human or mouse, reflecting low levels of inflammation. These differences between Spalax, human and mouse are due to several factors including the intensive activity life-style that Spalax pursue underground, dietary components, and evolutionary genetic adaptations. Unfolding the genetic basis of these differences will probably result in unique treatments for a variety of human diseases such as dyslipedemias, inflammation and cancer.

  13. Gln 192Arg polymorphism of the paraoxonase-1 gene is not associated with Alzheimer's disease in Chinese%对氧磷酶1基因Gln192Arg多态性与阿尔茨海默病的关联研究

    Institute of Scientific and Technical Information of China (English)

    施佳军; 张思仲; 马崔; 唐牟尼; 刘协和; 王英成; 韩海英; 郭扬波; 冯容妹; 苗国栋

    2004-01-01

    目的探讨对氧磷酶1(paraoxonase-1,PONI)基因Gln192Arg多态性与汉族散发阿尔茨海默病(AD)的关系.方法以165例散发AD患者和174例年龄匹配老年人为对象进行病例-对照研究.用PCR-RFLP法检测PONI及载脂蛋白E(ApoE)基因多态并进行关联分析.结果AD组与对照组PONI基因Gln1924rg多态性分布没有显著性差异.研究对象按ApoEε4携带状况分层后,各亚组之间基因多态性分布亦无显著性差异.结论PONI基因Gln19Arg多态性与中国汉族人群AD不存在关联.

  14. Protective role of L-carnitine supplementation against exhaustive exercise induced oxidative stress in rats.

    Science.gov (United States)

    Síktar, Elif; Ekinci, Deniz; Síktar, Erdinç; Beydemir, Sükrü; Gülçin, Ilhami; Günay, Mehmet

    2011-10-15

    The objective of this study was to investigate temperature dependent effects of oral l-carnitine supplementation on exhaustive exercise induced oxidative damage in rats. 42 male Spraque Dawley rats were randomly divided into seven experimental groups. These groups were formed as three non-carnitine exercise groups, three carnitine-exercise groups and a sedentary group. l-carnitine was given intraperitoneally to the carnitine-exercise groups 1h before the exercise in 100mg/kg. Blood was collected to measure paraoxonase-1 (PON1) activity, plasma malondialdehyde (MDA), low-density lipoprotein (LDL) and cholesterol concentrations. These biomarkers were measured in venous blood samples collected before and after the rats swam in pools at different water temperatures (18°C, 28°C and 38°C). In the non-carnitine group, exercise caused a significant decrease in PON1 activity and a significant elevation in MDA concentration at 28°C compared to the sedentary group. No significant alterations were evidenced in LDL and cholesterol concentrations upon exercise. The decrease in PON1 activity became higher with increasing temperature whereas the elevation in MDA levels increased at 18°C. In the l-carnitine supplementation group, recovery in PON1 activity was observed significant at 28°C and very significant at 38°C. MDA concentration was almost the same with that of the non-carnitine group at 18 and 38°C, but it significantly decreased at 28°C. Considering the recovery in PON1 and MDA levels at 28°C, which is the temperature of the sedentary group; our results suggest that l-carnitine supplementation has a protective role on exhaustive exercise-induced oxidative stress. Findings of this study also demonstrate influences of thermal stress on these parameters during exhaustive exercise.

  15. Kinetics of tris (1-chloro-2-propyl) phosphate (TCIPP) metabolism in human liver microsomes and serum.

    Science.gov (United States)

    Van den Eede, Nele; Tomy, Gregg; Tao, Fang; Halldorson, Thor; Harrad, Stuart; Neels, Hugo; Covaci, Adrian

    2016-02-01

    Tris(1-chloro-2-propyl) phosphate (TCIPP) is an emerging contaminant which is ubiquitous in the indoor and outdoor environment. Moreover, its presence in human body fluids and biota has been evidenced. Since no quantitative data exist on the biotransformation or stability of TCIPP in the human body, we performed an in vitro incubation of TCIPP with human liver microsomes (HLM) and human serum (HS). Two metabolites, namely bis(2-chloro-isopropyl) phosphate (BCIPP) and bis(1-chloro-2-propyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP), were quantified in a kinetic study using HLM or HS (only BCIPP, the hydrolysis product) and LC-MS. The Michaelis-Menten model fitted best the NADPH-dependent formation of BCIPHIPP and BCIPP in HLM, with respective V(MAX) of 154 ± 4 and 1470 ± 110 pmol/min/mg protein and respective apparent K(m) of 80.2 ± 4.4 and 96.1 ± 14.5 μM. Hydrolases, which are naturally present in HLM, were also involved in the production of BCIPP. A HS paraoxonase assay could not detect any BCIPP formation above 38.6 ± 10.8 pmol/min/μL serum. Our data indicate that BCIPP is the major metabolite of TCIPP formed in the liver. To our knowledge, this is the first quantitative assessment of the stability of TCIPP in tissues of humans or any other species. Further research is needed to confirm whether these biotransformation reactions are associated with a decrease or increase in toxicity.

  16. Protective Effect of R Allele of PON1 Gene on the Coronary Artery Disease in the Presence of Specific Genetic Background

    Directory of Open Access Journals (Sweden)

    Anna Balcerzyk

    2008-01-01

    Full Text Available Background: Genetic susceptibility to CAD may be determined by polymorphic variants of genes encoding isoforms involved in the processes important in the pathogenesis of atherosclerosis, including lipids disorders. Participation of single polymorphic variants is relatively small, however its significance may increase in the presence of specific genetic or environmental background.

  17. Olmesartan Combined With Amlodipine on Oxidative Stress Parameters in Type 2 Diabetics, Compared With Single Therapies: A Randomized, Controlled, Clinical Trial.

    Science.gov (United States)

    Derosa, Giuseppe; Mugellini, Amedeo; Pesce, Rosa Maria; D'Angelo, Angela; Maffioli, Pamela

    2016-03-01

    To evaluate the effects of a fixed combination of olmesartan/amlodipine compared with olmesartan or amlodipine alone on some parameters of endothelial damage in diabetic, hypertensive patients.We enrolled 221 patients; 74 were randomized to olmesartan 20 mg, 72 to amlodipine 10 mg, and 75 to olmesartan/amlodipine fixed combination 20/5 mg for 12 months. We assessed blood pressure monthly; in addition, we also assessed at baseline, and after 6 and 12 months, the following parameters: lipoprotein (a), myeloperoxidase (MPO), isoprostanes, and paraoxonase-1 (PON-1). Blood pressure values obtained with fixed olmesartan/amlodipine combination were significantly lower than those reached with single monotherapies. There was a reduction of lipoprotein (a), and isoprostanes levels with olmesartan/amlodipine fixed combination, both compared with baseline, and with single monotherapies. On the other hand, there was an increase of PON-1 with fixed olmesartan/amlodipine combination, both compared with baseline, and with single drugs. All treatments reduced MPO compared with baseline; however, in group-to-group comparison, MPO reduction was greater with olmesartan/amlodipine fixed combination. Fixed combination of olmesartan/amlodipine was more effective than single monotherapies in reducing oxidative stress, especially in increasing PON-1, and reducing isoprostanes levels in diabetic and hypertensive patients.

  18. Olmesartan Combined With Amlodipine on Oxidative Stress Parameters in Type 2 Diabetics, Compared With Single Therapies

    Science.gov (United States)

    Derosa, Giuseppe; Mugellini, Amedeo; Pesce, Rosa Maria; D’Angelo, Angela; Maffioli, Pamela

    2016-01-01

    Abstract To evaluate the effects of a fixed combination of olmesartan/amlodipine compared with olmesartan or amlodipine alone on some parameters of endothelial damage in diabetic, hypertensive patients. We enrolled 221 patients; 74 were randomized to olmesartan 20 mg, 72 to amlodipine 10 mg, and 75 to olmesartan/amlodipine fixed combination 20/5 mg for 12 months. We assessed blood pressure monthly; in addition, we also assessed at baseline, and after 6 and 12 months, the following parameters: lipoprotein (a), myeloperoxidase (MPO), isoprostanes, and paraoxonase-1 (PON-1). Blood pressure values obtained with fixed olmesartan/amlodipine combination were significantly lower than those reached with single monotherapies. There was a reduction of lipoprotein (a), and isoprostanes levels with olmesartan/amlodipine fixed combination, both compared with baseline, and with single monotherapies. On the other hand, there was an increase of PON-1 with fixed olmesartan/amlodipine combination, both compared with baseline, and with single drugs. All treatments reduced MPO compared with baseline; however, in group-to-group comparison, MPO reduction was greater with olmesartan/amlodipine fixed combination. Fixed combination of olmesartan/amlodipine was more effective than single monotherapies in reducing oxidative stress, especially in increasing PON-1, and reducing isoprostanes levels in diabetic and hypertensive patients. PMID:27043671

  19. Plasma Markers of Oxidative Stress in Patients with Gestational Diabetes Mellitus in the Second and Third Trimester

    Science.gov (United States)

    Ouyang, Zhenbo

    2016-01-01

    Objective. To determine plasma markers of oxidative stress during the second and third trimester of pregnancy in patients with gestational diabetes mellitus (GDM). Study Design. We conducted a prospective nested case-control study involving 400 pregnant women, 22 of whom developed GDM. As control group, 30 normal pregnant women were chosen randomly. Plasma samples were analyzed for 8-iso-prostaglandin F2α (8-iso-PGF2α), advanced oxidative protein products (AOPPs), protein carbonyl (PCO), glutathione peroxidase-3 (GPX-3), and paraoxonase-1 (PON1) at 16–20 weeks, 24–28 weeks, and 32–36 weeks of gestation. Results. Compared to control subjects, the plasma levels of PCO, AOPPs, and 8-iso-PGF2α were elevated at 16–20 weeks' and 32–36 weeks' gestation in GDM. There was no significant difference in PCO and 8-iso-PGF2α at 24–28 weeks in GDM. GPX-3 was statistically significantly increased at 16–20 weeks and 32–36 weeks in GDM. PON1 reduced in patients with GDM. No significant differences were found at 24–28 and 32–36 weeks between the GDM and control groups. In GDM, PCO, AOPPs, and 8-iso-PGF2α levels were higher and GPX-3 and PON1 levels were lower in the second than the third trimester. Conclusion. Oxidation status increased in GDM, especially protein oxidation, which may contribute to the pathogenesis of GDM. PMID:27803713

  20. Human See, Human Do.

    Science.gov (United States)

    Tomasello, Michael

    1997-01-01

    A human demonstrator showed human children and captive chimpanzees how to drag food or toys closer using a rakelike tool. One side of the rake was less efficient than the other for dragging. Chimps tried to reproduce results rather than methods while children imitated and used the more efficient rake side. Concludes that imitation leads to…

  1. Higher serum lipids and oxidative stress in patients with normal tension glaucoma, but not pseudoexfoliative glaucoma

    Science.gov (United States)

    Yilmaz, Necat; Coban, Deniz Turgut; Bayindir, Asli; Erol, Muhammet Kazim; Ellidag, Hamit Yasar; Giray, Ozlem; Sayrac, Suha; Tekeli, Seckin Ozgur; Eren, Esin

    2016-01-01

    This study entailed a cross-examination of oxidant/antioxidant balance, high-density lipoprotein (HDL)-linked paraoxonase 1 (PON1) phenotypes, and levels of serum routine lipids among patients with normal tension glaucoma (NTG) or pseudoexfoliative glaucoma (PEXG) compared with healthy control groups. We aimed to investigate the links between oxidative stress (OS), HDL-related antioxidant enzyme activities and dyslipidemia in distinct subtypes of glaucoma. The study included 32 patients with NTG, 31 patients with PEXG, and 40 control subjects. Levels of PON1 and arylesterase enzymatic activity, total oxidant status (TOS), and total antioxidant status were measured by spectrophotometry and OS indexes (OSI) were calculated. The phenotype distribution of PON1 was determined using the dual substrate method. Blood serum levels of HDL, low-density lipoprotein, total cholesterol (TC), and triglyceride (TG) were measured. The TOS and OSI values in the NTG group were significantly higher compared with the other groups (both p < 0.01). The phenotype distribution found in the glaucoma and control groups were NTG: QQ, 59.4%; QR, 37.5%; RR, 3.1%; PEXG: QQ, 45.1%; QR, 48.4%; RR, 6.5%; and in the control group: QQ, 42.5%; QR, 50.0%; RR, 7.5%. Serum TC levels were significantly higher than the control in both NTG and PEXG groups, whereas TG was significantly higher in NTG only (p < 0.01 and p < 0.02, respectively). Hyperlipidemia, OS and variations in phenotype distribution of PON1 may play a role in the pathogenesis of different types of glaucoma. PMID:26773174

  2. Higher serum lipids and oxidative stress in patients with normal tension glaucoma, but not pseudoexfoliative glaucoma

    Directory of Open Access Journals (Sweden)

    Necat Yilmaz

    2016-01-01

    Full Text Available This study entailed a cross-examination of oxidant/antioxidant balance, high-density lipoprotein (HDL-linked paraoxonase 1 (PON1 phenotypes, and levels of serum routine lipids among patients with normal tension glaucoma (NTG or pseudoexfoliative glaucoma (PEXG compared with healthy control groups. We aimed to investigate the links between oxidative stress (OS, HDL-related antioxidant enzyme activities and dyslipidemia in distinct subtypes of glaucoma. The study included 32 patients with NTG, 31 patients with PEXG, and 40 control subjects. Levels of PON1 and arylesterase enzymatic activity, total oxidant status (TOS, and total antioxidant status were measured by spectrophotometry and OS indexes (OSI were calculated. The phenotype distribution of PON1 was determined using the dual substrate method. Blood serum levels of HDL, low-density lipoprotein, total cholesterol (TC, and triglyceride (TG were measured. The TOS and OSI values in the NTG group were significantly higher compared with the other groups (both p < 0.01. The phenotype distribution found in the glaucoma and control groups were NTG: QQ, 59.4%; QR, 37.5%; RR, 3.1%; PEXG: QQ, 45.1%; QR, 48.4%; RR, 6.5%; and in the control group: QQ, 42.5%; QR, 50.0%; RR, 7.5%. Serum TC levels were significantly higher than the control in both NTG and PEXG groups, whereas TG was significantly higher in NTG only (p < 0.01 and p < 0.02, respectively. Hyperlipidemia, OS and variations in phenotype distribution of PON1 may play a role in the pathogenesis of different types of glaucoma.

  3. More Human than Human.

    Science.gov (United States)

    Lawrence, David

    2017-07-01

    Within the literature surrounding nonhuman animals on the one hand and cognitively disabled humans on the other, there is much discussion of where beings that do not satisfy the criteria for personhood fit in our moral deliberations. In the future, we may face a different but related problem: that we might create (or cause the creation of) beings that not only satisfy but exceed these criteria. The question becomes whether these are minimal criteria, or hierarchical, such that those who fulfill them to greater degree should be afforded greater consideration. This article questions the validity and necessity of drawing divisions among beings that satisfy the minimum requirements for personhood; considering how future beings-intelligent androids, synthezoids, even alternate-substrate sentiences-might fit alongside the "baseline" human. I ask whether these alternate beings ought to be considered different to us, and why this may or may not matter in terms of a notion of "human community." The film Blade Runner, concerned in large part with humanity and its key synthezoid antagonist Roy Batty, forms a framing touchstone for my discussion. Batty is stronger, faster, more resilient, and more intelligent than Homo sapiens. His exploits, far beyond the capability of normal humans, are contrasted with his frailty and transient lifespan, his aesthetic appreciation of the sights he has seen, and his burgeoning empathy. Not for nothing does his creator within the mythos term him "more human than human."

  4. Relations between Paraoxonase Activities and Malondialdehyde with Lipid Profile in Pre-eclampsia%子痫前期患者血清对氧磷酶活性及脂质过氧化与血脂变化的相关性研究

    Institute of Scientific and Technical Information of China (English)

    岳文芳; 李季滨; 李丽; 范爱华; 王丽琴

    2011-01-01

    Objective To investigate the relationship between paraoxonase activities ( PON ) and Malondialdehyde ( MDA ) and lipid profile in pre - eclampsia and the severity of pre - eclampsia. Methods 60 PE pregnant women were involved in the study as experiment group, and 40 healthy pregnant women in advanced stage were involved as control study. The changes of the levels of PON activity , MDA and lipid profile in the serum of the patients with pre - eclampsia were detected. Results Compared with that of patients with mild pre-eclampsia group [ ( 115. 80 ± 27. 25 ) kU/L ], the serum PON activity of patients with severe pre - eclampsia group [ ( 81. 86 ± 29. 68 ) kU/L ] was significantly lower ( P < 0. 01 ). The serum PON activity in the mild pre - eclampsia group was significantly lower than that of the patients in the control group ( P <0. 05 ). Compared with those of mild preeclampsia group [ ( 5. 16 ± 1. 02 ) nmol/L ] , the serum MDA of severe preeclampsia group [ ( 7. 11± 1. 52 ) nmol/L ] were significantly higher ( P <0. 01 ). The serum MDA levels in the mild preeclampsia group were also significantly higher than those in the control group ( P <0. 05 ). The serum TG and LDL-C levels in the experiment group were significantly higher than those in the control group ( P < 0. 05 ). The serum HDL - C level in the experiment group was significantly lower than that in the control group ( P <0. 05 ). Conclusion The PON activity, MDA and lipid profile of the patients with pre- eclampsia is related to the pathogenesis as well as the severity of preeclampsia.%目的 探讨血清中对氧磷酶(PON)活性,脂质过氧化物(丙二醛)对子痫前期(PE)患者血脂变化的影响及其与病情严重程度的相关性. 方法 入选60例PE孕妇作为试验组,健康孕晚期妇女40例作为对照组.分别检测两组受试者血清中PON活性,脂质过氧化物与血脂变化情况.结果 重度PE组患者PON活性[(81.86±29.68)kU/L]较轻度PE组[(115.80±27

  5. Human Development, Human Evolution.

    Science.gov (United States)

    Smillie, David

    One of the truly remarkable events in human evolution is the unprecedented increase in the size of the brain of "Homo" over a brief span of 2 million years. It would appear that some significant selective pressure or opportunity presented itself to this branch of the hominid line and caused a rapid increase in the brain, introducing a…

  6. Changes of Serum Paraoxonasel Activities and Metabolic Syndrome Varibles in Preeclamptic Women%子痫前期对氧磷酶1活性和代谢综合征变量变化的临床研究

    Institute of Scientific and Technical Information of China (English)

    董淑晓; 王立方; 辛虹

    2011-01-01

    目的:研究子痫前期患者血清对氧磷酶1(PON-1)活性及代谢综合征变量的变化和发生情况.方法:选择年龄、孕周、产次相匹配的轻度子痫前期患者38例(MPE组),重度子痫前期患者45例(SPE组),正常孕妇63例(对照组)为研究对象,测定其血清PON-1活性、丙二醛( MDA)、血脂及空腹血糖水平等指标.结果:子痫前期患者(MPE组+SPE组)血清MDA、总胆固醇、甘油三酯、低密度脂蛋白水平(LDL)均明显高于对照组(P<0.05),而血清PON-1活性及高密度脂蛋白( HDL)较对照组明显降低(P<0.05);SPE组空腹血糖较MPE组和对照组明显升高(P均<0.05).子痫前期患者血清PON-1活性与MDA、甘油三酯、LDL水平呈负相关(P均<0.05),与HDL水平呈正相关(P<0.05),与BMI及空腹血糖无明显相关性(P>0.05).对照组、MPE组及SPE组代谢综合征的发生率分别为3.2%,18.4%,33.3%.结论:子痫前期患者有代谢综合征的标志,推断两种疾病相互关联.子痫前期患者血清PON-1活性显著降低,可能为两种疾病相互关联的重要原因之一.%Objective:To explore the activity of paraoxonase and changes of metabolic syndrome variables in preeclamptic women. Methods :38 pregnant women with mild preeclampsia (MPE), 45 women with severe preeclampsia (SPE), and 63 normal pregnant women as control were recruited in this study after the age, gestination age and parity were matched. Fasting serum paraoxonase (PON1) activity was determined, as well as malondialdehyde (MDA), plasma lipids, fasting blood glucose and blood pressure. Results: Patients with preeclampsia had significantly higher serum MDA, total cholesterol, triglycerides, low density lipoprotein levels compared with the control group (P0. 05). The incidence of metabolic syndrome in control group, MPE and SPE were 3.2%, 18.4%, 33.3% respectively. Conclusions: Preeclampsia presents the characteristics of metabolic syndrome, so these are two correlated disease

  7. Human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2006-01-01

    Human rights reflect a determined effort to protect the dignity of each and every human being against abuse of power. This endeavour is as old as human history. What is relatively new is the international venture for the protection of human dignity through internationally accepted legal standards an

  8. Human Rights, Human Needs, Human Development, Human Security

    OpenAIRE

    Gasper, Des

    2009-01-01

    Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

  9. Brain SPECT imaging and whole-body biodistribution with [{sup 123}I]ADAM - a serotonin transporter radiotracer in healthy human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Lin, K.-J. [Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Tao-Yuan 333, Taiwan (China); Molecular Imaging Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Department of Nuclear Medicine, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Liu, C.-Y. [Neuroscience Research Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Department of Psychiatry, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Wey, S.-P. [Molecular Imaging Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang-Gung University, Tao-Yuan 333, Taiwan (China); Hsiao, I.-T. [Molecular Imaging Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang-Gung University, Tao-Yuan 333, Taiwan (China); Wu, Jay [Health Physics Divisions, Atomic Energy Council, Institute of Nuclear Energy Research, Tao-Yuan 325, Taiwan (China); Fu, Y.-K. [Atomic Energy Council, Institute of Nuclear Energy Research, Tao-Yuan 325, Taiwan (China); Yen, T.-C. [Molecular Imaging Center, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China) and Department of Nuclear Medicine, Chang-Gung Memorial Hospital, Tao-Yuan 333, Taiwan (China)]. E-mail: yen1110@adm.cgmh.org.tw

    2006-02-15

    Introduction: [{sup 123}I]-2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ([{sup 123}I]ADAM), a novel radiotracer, has promising application in the imaging of the serotonin transporter (SERT) in the human brain. In this study, the optimal scanning time for acquiring brain single photon emission computed tomography (SPECT) images was determined by performing dynamic SPECT studies at intervals from 0 to 6 h postinjection of [{sup 123}I]ADAM. Additionally, radiation-absorbed doses were determined for three healthy human subjects using attenuation-corrected images. Methods: Twelve subjects were randomized into one of three study groups as follows: whole-body distribution imaging (n=3), dynamic SPECT imaging (n=3) and brain SPECT imaging (n=6). The radiation-absorbed dose was calculated using MIRDOSE 3.0 software with attenuation-corrected data. The specific binding (SB) ratio of the brain stem was measured from dynamic SPECT images to determine the optimal scanning time. Results: Dynamic SPECT images showed that the SB of the brain stem gradually increased to a maximum 4 h postinjection. Single photon emission computed tomography images at 4 h postinjection showed a high uptake of the radiotracer (SB) in the hypothalamus (1.40{+-}0.12), brain stem (1.44{+-}0.16), pons (1.13{+-}0.14) and medial temporal lobe (0.59{+-}0.10). The mean adult male value of effective dose was 3.37x10{sup -2} mSv/MBq with a 4.8-h urine-voiding interval. Initial high uptake in SERT-rich sites was demonstrated in the lung and brain. A prominent washout of the radiotracer from the lung further increased brain radioactivity that reached a peak value of 5.03% of injected dose 40 min postinjection. Conclusions: [{sup 123}I]ADAM is a promising radiotracer for SPECT imaging of SERT in humans with acceptable dosimetry and high uptake in SERT-rich regions. Brain SPECT images taken within 4 h following injection show optimal levels of radiotracer uptake in known SERT sites. However, dynamic

  10. Human Technology and Human Affects

    DEFF Research Database (Denmark)

    Fausing, Bent

    2009-01-01

    Human Technology and Human Affects  This year Samsung introduced a mobile phone with "Soul". It was made with a human touch and included itself a magical touch. Which function does technology and affects get in everyday aesthetics like this, its images and interactions included this presentation ...... often mentioned post-human condition....

  11. Human microbiomics

    OpenAIRE

    Rajendhran, J.; P. Gunasekaran

    2010-01-01

    The sequencing of the human genome has driven the study of human biology in a significant way and enabled the genome-wide study to elucidate the molecular basis of complex human diseases. Recently, the role of microbiota on human physiology and health has received much attention. The influence of gut microbiome (the collective genomes of the gut microbiota) in obesity has been demonstrated, which may pave the way for new prophylactic and therapeutic strategies such as bacteriotherapy. The sig...

  12. Human Smuggling

    NARCIS (Netherlands)

    Siegel - Rozenblit, Dina; Zaitch, Damian

    2014-01-01

    Human smuggling is based on a consensus between smuggler, smuggled, and his/her family (which usually guarantees or effectuates payment). However, unauthorized immigrants are violating immigration laws and human smugglers are profiting from enabling illegal immigration. Both human smuggling and its

  13. Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients

    Institute of Scientific and Technical Information of China (English)

    El(z)bieta KIMAK; Magdalena HA(L)ABI(S); Iwona BARANOWICZ-GA SZCZYK; Janusz SOLSKI; Andrzej KSIA(Z)EK

    2011-01-01

    Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle,oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy.HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-Ⅰ (apoA-Ⅰ) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C,apoA-Ⅰ/apoB, HDL-C/apoA-Ⅰ, TG/HDL) were atherogenic. The Spearman's rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=-0.306, P=0.012), LDL-C (R=-0.283, P=0.020), and non-HDL-C (R=-0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre

  14. Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients.

    Science.gov (United States)

    Kimak, Elżbieta; Hałabiś, Magdalena; Baranowicz-Gąszczyk, Iwona; Solski, Janusz; Książek, Andrzej

    2011-05-01

    Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I (apoA-I) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL) were atherogenic. The Spearman's rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=-0.306, P=0.012), LDL-C (R=-0.283, P=0.020), and non-HDL-C (R=-0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-β-HDL particles

  15. Analogues with fluorescent leaving groups for screening and selection of enzymes that efficiently hydrolyze organophosphorus nerve agents.

    Science.gov (United States)

    Briseño-Roa, Luis; Hill, Jim; Notman, Stuart; Sellers, David; Smith, Andy P; Timperley, Christopher M; Wetherell, Janet; Williams, Nichola H; Williams, Gareth R; Fersht, Alan R; Griffiths, Andrew D

    2006-01-12

    Enzymes that efficiently hydrolyze highly toxic organophosphorus nerve agents could potentially be used as medical countermeasures. As sufficiently active enzymes are currently unknown, we synthesized twelve fluorogenic analogues of organophosphorus nerve agents with the 3-chloro-7-oxy-4-methylcoumarin leaving group as probes for high-throughput enzyme screening. This set included analogues of the pesticides paraoxon, parathion, and dimefox, and the nerve agents DFP, tabun, sarin, cyclosarin, soman, VX, and Russian-VX. Data from inhibition of acetylcholinesterase, in vivo toxicity tests of a representative analogue (cyclosarin), and kinetic studies with phosphotriesterase (PTE) from Pseudomonas diminuta, and a mammalian serum paraoxonase (PON1), confirmed that the analogues mimic the parent nerve agents effectively. They are suitable tools for high-throughput screens for the directed evolution of efficient nerve agent organophosphatases.

  16. Human Rights/Human Needs.

    Science.gov (United States)

    Canning, Cynthia

    1978-01-01

    The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

  17. Study of the relationship between APOA-II -265T>C polymorphism and HDL function in response to weight loss in overweight and obese type 2 diabetic patients.

    Science.gov (United States)

    Moradi, Masoumeh; Mahmoudi, Maryam; Saedisomeolia, Ahmad; Mansournia, Mohammad Ali; Zahirihashemi, Roxana; Koohdani, Fariba

    2017-04-09

    It has been reported that people may respond differently to the same environmental changes because of genome variations. The main purpose of the present study is to determine gene-diet interactions between -265T>C apolipoprotein A-II polymorphisms and evaluate the effect of weight loss on parameters related to HDL function. In the present study, 56 overweight and obese type 2 diabetic patients were chosen from 697 genotype-specified subjects. After matching for gender, age and BMI, an equal number of patients were chosen for each genotype of APOA-II (TT/TC and CC group). After six-week calorie restriction programme, 44 patients completed the study. Serum paraoxonase-1 (PON1), paraoxonase-3 (PON3), pentraxin-3 (PTX3), and PTX3 gene expression in peripheral blood mononuclear cells were compared between two genotypes and also before and after the intervention separated in each genotype. The mean differences of PON enzymes and PTX3 between groups were not significant at the baseline. After weight loss, the mean weight, BMI and serum concentration of PON1 and PON3 decreased significantly and PTX3 increased in total population. Although, the mean differences of PON enzymes and PTX3 between two groups were not significant. However, in comparison of mean differences within the groups, decreased PON3 and increased PTX3 have been observed only in TT group. A comparison of the mean differences in PON3 and PTX3 within two genotype groups showed that T allele carriers are more sensitive to lifestyle modification, and serum PON3 and PTX3 levels significantly changed only in the TT/TC group. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  18. Digital Humanities

    DEFF Research Database (Denmark)

    Brügger, Niels

    2016-01-01

    the humanities for decades, starting with research fields such as humanities computing or computational linguistics in the 1950s, and later new media studies and internet studies. The historical development of digital humanities has been characterized by a focus on three successive, but co-existing types......Digital humanities is an umbrella term for theories, methodologies, and practices related to humanities scholarship that use the digital computer as an integrated and essential part of its research and teaching activities. The computer can be used for establishing, finding, collecting......, and preserving material to study, as an object of study in its own right, as an analytical tool, or for collaborating, and for disseminating results. The term "digital humanities" was coined around 2001, and gained currency within academia in the following years. However, computers had been used within...

  19. Human Rights, Human Needs, Human Development, Human Security - Relationships between four international human discourses.

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    markdownabstractAbstract: Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and

  20. Protective effects of ginseng extracts and common anti-aggregant drugs on ischaemia-reperfusion injury.

    Science.gov (United States)

    Caliskan, Ahmet; Karahan, Oguz; Yazici, Suleyman; Demirtas, Sinan; Guclu, Orkut; Tezcan, Orhan; Yavuz, Celal

    2015-01-01

    Ginseng is a traditional herbal medicinal product widely used for various types of diseases because of its cellular protective effects. Possible protective effects of ginseng were investigated in blood, cardiac and renal tissue samples and compared with common anti-aggregant agents in an animal ischaemia-reperfusion (I/R) model. Twenty rats were equally divided into four different groups as follows: control group (I/R-induced group without drug use), group I (acetylsalicylic acid-administered group), group II (clopidogrel bisulfate-administered group), group III (ginsenoside Rb1-administered group). For the groups assigned to a medication, peripheral I/R was induced by clamping the femoral artery one week after initiation of the specified medication. After reperfusion was initiated, cardiac and renal tissues and blood samples were obtained from each rat with subsequent analysis of nitrogen oxide (NOx), malondialdehyde (MDA), paraoxonase 1 (PON1) and prolidase. NOx levels were similar in each group. Significant decrements were observed in serum PON1 levels in each group when compared with the control (p ginseng extracts may have a potential beneficial effect in I/R injury. However, more comprehensive studies are required to clarify the hypothetical cardiac, renal and systemic protective effects in reperfusion-induced oxidative damage.

  1. The Oxidant and Antioxidant Status in Pityriasis Rosea

    Science.gov (United States)

    Emre, Selma; Akoglu, Gulsen; Metin, Ahmet; Demirseren, Duriye Deniz; Isikoglu, Semra; Oztekin, Aynure; Erel, Ozcan

    2016-01-01

    Background: Pityriasis rosea (PR) is usually an asymptomatic and self-limiting papulosquamous skin disease with acute onset. The etiology has not been clarified yet. Recently, increased oxidative stress was found to play a role in etiopathogenesis of multiple cutaneous diseases with T cell-mediated immune response. However, there are no studies demonstrating the oxidative stress status in PR. Aim: The aim of the study is to determine the status of oxidative stress (OS) and paraoxonase (PON) 1/arylesterase enzyme activities in PR. Materials and Methods: Study included 51 patients with active PR lesions, and 45 healthy volunteers. Serum levels of total oxidant status (TOS), total antioxidant status (TAS), and PON1/arylesterase (ARES) activity were determined and oxidative stress index (OSI) was calculated in all patients and controls. Results: TAS levels and ARES activities in the patient group were significantly lower than the control group. On the other hand, TOS and OSI levels were significantly higher in patients compared with controls. There was no significant correlation between the duration of disease and TAS, TOS, OSI levels, and ARES activities. Conclusion: A systemic oxidative stress exists in PR, which suggests that OS may be involved in the etiopathogenesis of disease. PMID:26955119

  2. The oxidant and antioxidant status in pityriasis rosea

    Directory of Open Access Journals (Sweden)

    Selma Emre

    2016-01-01

    Full Text Available Background: Pityriasis rosea (PR is usually an asymptomatic and self-limiting papulosquamous skin disease with acute onset. The etiology has not been clarified yet. Recently, increased oxidative stress was found to play a role in etiopathogenesis of multiple cutaneous diseases with T cell-mediated immune response. However, there are no studies demonstrating the oxidative stress status in PR. Aim: The aim of the study is to determine the status of oxidative stress (OS and paraoxonase (PON 1/arylesterase enzyme activities in PR. Materials and Methods: Study included 51 patients with active PR lesions, and 45 healthy volunteers. Serum levels of total oxidant status (TOS, total antioxidant status (TAS, and PON1/arylesterase (ARES activity were determined and oxidative stress index (OSI was calculated in all patients and controls. Results: TAS levels and ARES activities in the patient group were significantly lower than the control group. On the other hand, TOS and OSI levels were significantly higher in patients compared with controls. There was no significant correlation between the duration of disease and TAS, TOS, OSI levels, and ARES activities. Conclusion: A systemic oxidative stress exists in PR, which suggests that OS may be involved in the etiopathogenesis of disease.

  3. Effect of spermine on lipid profile and HDL functionality in the streptozotocin-induced diabetic rat model.

    Science.gov (United States)

    Jafarnejad, A; Bathaie, S Z; Nakhjavani, M; Hassan, M Z

    2008-01-30

    This study aimed to investigate the effect of spermine (Spm) as a chemical chaperone and glycation inhibitor on the lipid profile and HDL functionality in the short- and long-term treatment of the STZ-induced diabetic rats. Male Wistar rats were divided into 4 groups (control, n=7; diabetic, n=9). Two groups (named 2 and 3) were injected intraperitoneally with streptozotocin. Control rats (named 1 and 4) were injected with vehicle alone. The treatment of diabetic and control animals (groups 3 and 4) with 60 micromol/l of Spm in drinking water was begun. The study continued up to the end of the fifth month. The serum glucose and insulin level, AGE formation, lipid profile, paraoxonase 1 (PON1), and lecithin: cholesterol acyl transferase (LCAT) activities were measured. Significantly lower plasma PON1, and LCAT activities and higher serum AGE, TG, TC and LDL-c, and lower HDL-c were seen in diabetic rats as compared to control groups (Pdiabetic groups decreased gradually after receiving Spm. In addition, due to Spm administration, an increase in the HDL-c level was observed after the first month of the experiment (Pdiabetic group that received Spm was significant after the second and the forth month of the experiment, Pdiabetic rats. Spermine, despite a lack of significant changes on glucose metabolism and insulin secretion, was found to improve diabetes complications.

  4. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease

    Science.gov (United States)

    Besler, Christian; Heinrich, Kathrin; Rohrer, Lucia; Doerries, Carola; Riwanto, Meliana; Shih, Diana M.; Chroni, Angeliki; Yonekawa, Keiko; Stein, Sokrates; Schaefer, Nicola; Mueller, Maja; Akhmedov, Alexander; Daniil, Georgios; Manes, Costantina; Templin, Christian; Wyss, Christophe; Maier, Willibald; Tanner, Felix C.; Matter, Christian M.; Corti, Roberto; Furlong, Clement; Lusis, Aldons J.; von Eckardstein, Arnold; Fogelman, Alan M.; Lüscher, Thomas F.; Landmesser, Ulf

    2011-01-01

    Therapies that raise levels of HDL, which is thought to exert atheroprotective effects via effects on endothelium, are being examined for the treatment or prevention of coronary artery disease (CAD). However, the endothelial effects of HDL are highly heterogeneous, and the impact of HDL of patients with CAD on the activation of endothelial eNOS and eNOS-dependent pathways is unknown. Here we have demonstrated that, in contrast to HDL from healthy subjects, HDL from patients with stable CAD or an acute coronary syndrome (HDLCAD) does not have endothelial antiinflammatory effects and does not stimulate endothelial repair because it fails to induce endothelial NO production. Mechanistically, this was because HDLCAD activated endothelial lectin-like oxidized LDL receptor 1 (LOX-1), triggering endothelial PKCβII activation, which in turn inhibited eNOS-activating pathways and eNOS-dependent NO production. We then identified reduced HDL-associated paraoxonase 1 (PON1) activity as one molecular mechanism leading to the generation of HDL with endothelial PKCβII-activating properties, at least in part due to increased formation of malondialdehyde in HDL. Taken together, our data indicate that in patients with CAD, HDL gains endothelial LOX-1– and thereby PKCβII-activating properties due to reduced HDL-associated PON1 activity, and that this leads to inhibition of eNOS-activation and the subsequent loss of the endothelial antiinflammatory and endothelial repair–stimulating effects of HDL. PMID:21701070

  5. Molecular Evolution of Human PON to Design Enhanced Catalytic Efficiency for Hydrolysis of Nerve Agents

    Science.gov (United States)

    2011-12-01

    Sussman, J.L., Tawfik, D.S. The use of recombinant paraoxonases as bioscavengers for the pretreatment/treatment of organophosphate poisoning , 13th...2006). 10. Bird, S.B., Dawson, A. & Ollis, D. Enzymes and bioscavengers for prophylaxis and treatment of organophosphate poisoning . Front. Biosci...intercepting both existing and emerging organophosphate -based chemical warfare nerve agents (CWNA). The 5 years of performance under this project

  6. Citric acid effects on brain and liver oxidative stress in lipopolysaccharide-treated mice.

    Science.gov (United States)

    Abdel-Salam, Omar M E; Youness, Eman R; Mohammed, Nadia A; Morsy, Safaa M Youssef; Omara, Enayat A; Sleem, Amany A

    2014-05-01

    Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-α) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-α, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

  7. Human Rights and Human Nature

    Directory of Open Access Journals (Sweden)

    Vittorio Possenti

    2013-11-01

    Full Text Available There seems to be two different versions of human rights in Western tradition: say Rationalistic and Christian; the former adopted in revolutionary France, the latter highly developed in Renaissance Spain. Current relativistic criticisms attempt to deny the universality of human rights alleging that this theory has been created in Western countries or it has no strong justification, and therefore cannot have universal approach; but this objection can be dismissed with an alternative justification of human rights.

  8. Human kapital

    DEFF Research Database (Denmark)

    Grosen, Anders; Nielsen, Peder Harbjerg

    2007-01-01

    finansiel og human kapital. Den traditionelle rådgivnings snævre synsvinkel kan føre til forkerte investeringsråd. Der skal derfor opfordres til, at de finansielle virksomheder i tilrettelæggelsen af deres rådgivning af private kunder systematisk inddrager den humane kapitals størrelse og karakteristika i...

  9. Human trichuriasis

    DEFF Research Database (Denmark)

    Betson, Martha; Søe, Martin Jensen; Nejsum, Peter

    2015-01-01

    Human trichuriasis is a neglected tropical disease which affects hundreds of millions of people worldwide and is particularly prevalent among children living in areas where sanitation is poor. This review examines the current knowledge on the taxonomy, genetics and phylogeography of human Trichuris...

  10. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...... with the human-centered theory of communication advocated by integrationism....

  11. Human evolution

    DEFF Research Database (Denmark)

    Llamas, Bastien; Willerslev, Eske; Orlando, Ludovic Antoine Alexandre

    2017-01-01

    , and true population genomic studies of Bronze Age populations. Among the emerging areas of aDNA research, the analysis of past epigenomes is set to provide more new insights into human adaptation and disease susceptibility through time. Starting as a mere curiosity, ancient human genetics has become...

  12. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...... with the human-centered theory of communication advocated by integrationism....

  13. Teaching humanism.

    Science.gov (United States)

    Stern, David T; Cohen, Jordan J; Bruder, Ann; Packer, Barbara; Sole, Allison

    2008-01-01

    As the "passion that animates authentic professionalism," humanism must be infused into medical education and clinical care as a central feature of medicine's professionalism movement. In this article, we discuss a current definition of humanism in medicine. We will also provide detailed descriptions of educational programs intended to promote humanism at a number of medical schools in the United States (and beyond) and identify the key factors that make these programs effective. Common elements of programs that effectively teach humanism include: (1) opportunities for students to gain perspective in the lives of patients; (2) structured time for reflection on those experiences; and (3) focused mentoring to ensure that these events convert to positive, formative learning experiences. By describing educational experiences that both promote and sustain humanism in doctors, we hope to stimulate the thinking of other medical educators and to disseminate the impact of these innovative educational programs to help the profession meet its obligation to provide the public with humanistic physicians.

  14. Human Computation

    CERN Document Server

    CERN. Geneva

    2008-01-01

    What if people could play computer games and accomplish work without even realizing it? What if billions of people collaborated to solve important problems for humanity or generate training data for computers? My work aims at a general paradigm for doing exactly that: utilizing human processing power to solve computational problems in a distributed manner. In particular, I focus on harnessing human time and energy for addressing problems that computers cannot yet solve. Although computers have advanced dramatically in many respects over the last 50 years, they still do not possess the basic conceptual intelligence or perceptual capabilities...

  15. Practicing Humanities

    DEFF Research Database (Denmark)

    Gimmler, Antje

    2016-01-01

    In contemporary societies, the humanities are under constant pressure and have to justify their existence. In the ongoing debates, Humboldt’s ideals of ‘Bildung’ and ‘pure science’ are often used to justify the unique function of the humanities of ensuring free research and contributing to a vital...... philosophy. Contrary to Humboldt’s idea that the non-practical is the most practical in the long run, philosophical pragmatism recommends to the humanities to situate knowledge in practices and apply knowledge to practices....

  16. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  17. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    . The first section of this chapter outlines the complete cause-effect pathway, from emissions of toxic substances to intake by the population up to damages in terms of human health effects. Section 2 outlines the framework for assessing human toxicity in LCIA. Section 3 discusses the contributing substances......This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... – demonstrates the importance to account for both outdoor and indoor exposure, including consumer products. Analysing the variations in intake fraction (the fraction of the emitted or applied chemical that is taken in by the consumer and the general population), effect factor and characterisation factor across...

  18. Human influences

    NARCIS (Netherlands)

    Lanen, van H.A.J.; Kasparek, L.; Novicky, O.; Querner, E.P.; Fendeková, M.; Kupczyk, E.

    2004-01-01

    Human activities can cause drought, which was not previously reported (man-induced hydrological drought). Groundwater abstractions for domestic and industrial use are a well-known example of such an environmental change

  19. Human phantom

    CERN Multimedia

    CERN PhotoLab

    1973-01-01

    This human phantom has been received by CERN on loan from the State Committee of the USSR for the Utilization of Atomic Energy. It is used by the Health Physics Group to study personel radiation doses near the accelerators.

  20. Human expunction

    Science.gov (United States)

    Klee, Robert

    2017-10-01

    Thomas Nagel in `The Absurd' (Nagel 1971) mentions the future expunction of the human species as a `metaphor' for our ability to see our lives from the outside, which he claims is one source of our sense of life's absurdity. I argue that the future expunction (not to be confused with extinction) of everything human - indeed of everything biological in a terran sense - is not a mere metaphor but a physical certainty under the laws of nature. The causal processes by which human expunction will take place are presented in some empirical detail, so that philosophers cannot dismiss it as merely speculative. I also argue that appeals to anthropic principles or to forms of mystical cosmology are of no plausible avail in the face of human expunction under the laws of physics.

  1. Human babesiosis.

    Science.gov (United States)

    Rożej-Bielicka, Wioletta; Stypułkowska-Misiurewicz, Hanna; Gołąb, Elżbieta

    2015-01-01

    Babesiosis is an emerging parasitic, anthropo-zoonotic tick-borne disease, seldom diagnosed in humans. Caused by Protozoa, Babesia (also called Piroplasma) intraerytrocytic piriform microorganism. Infection of vertebrates is transmitted by ticks. Out of more than 100 Babesia species/genotypes described so far, only some were diagnosed in infected humans, mostly B. microti, B. divergens and B. venatorum (Babesia sp. EU1). Infection in humans is often asymptomatic or mild but is of a particular risk for asplenic individuals, those with congenital or acquired immunodeficiencies, and elderly. Infections transmitted with blood and blood products raise concerns in hemotherapy. Epidemiological situation of babesiosis varies around the world. In Europe, no increase in the number of cases was reported, but in the USA its prevalence is increasing and extension of endemic areas is observed. The aim of this publication is to describe the problems connected with the current epidemiological situation, diagnosis and treatment of human babesiosis with regard to clinical status of patients.

  2. Human energy

    OpenAIRE

    2010-01-01

    In the midst of big-oil record profits and growing debate on global warming, the Chevron Corporation launched its “Human Energy” public relations campaign. In television commercials and print advertisements, Chevron portrays itself as a compassionate entity striving to solve the planet’s energy crisis. Yet, the first term in this corporate oxymoron misleadingly reframes the significance of the second, suggesting that the corporation has a renewed focus. In depicting Chevron as a green/human o...

  3. Human Echolocation

    OpenAIRE

    Teng, Santani

    2013-01-01

    The use of active natural echolocation as a mobility aid for blind humans has received increased scientific and popular attention in recent years (Engber, 2006; Kreiser, 2006; NPR, 2011), in part due to a focus on several blind individuals who have developed remarkable expertise. However, perhaps surprisingly, the history of empirical human echolocation research is not much younger than the era of echolocation research (cf. Griffin, 1958). Nevertheless, compared to its bat and cetacean count...

  4. Human ehrlichiosis

    Directory of Open Access Journals (Sweden)

    Đokić Milomir

    2006-01-01

    Full Text Available Background. Human ehrlichiosis is a newly recognized disease. It is a tick-borne disease caused by several bacterial species of the genhus Erlichia. These are small gram-negative pleomorphic cocci, that are obligatory intracellular bacteria. Tick Ixodes is the principle vector in Europe, and Amblyomma americanum in the United States. Bacterial organisms replicate in a tick, and are transmited from infected cells in a vector to the blood cells of animals or humans. Human ehrlichiosis is a name for a group of diseases caused by different species of Ehrlichia. One of them is the disease named human monocytic ehrlichiosis, caused by Ehrlichia chaffeensis, and the other is a human granulocytic ehrlichiosis caused by Anaplasma phagocytophilia. Case report. We reported a 23-year-old patient admitted for the clinical treatment with the symptoms of high febrility (above 40 °C, headache, vomiting, general weakness and exhaustion, but without data on a tick bite. The patient was treated with trimetoprim-sulfamethoxazole for a week when Ehrlichia chaffeensis was confirmed by the immunofluoroscence test, and the therapy contimed with doxacyclin. Conclusion. Human ehrlichiosis is also present in our country, so this disease should be considered everyday, especially in infectology practice.

  5. [Human influenza].

    Science.gov (United States)

    Stock, Ingo

    2006-10-01

    Human influenza is one of the most common human infectious diseases, contributing to approximately one million deaths every year. In Germany, each year between 5.000 and 20.000 individuals die from severe influenza infections. In several countries, the morbidity and mortality of influenza is greatly underestimated. This is reflected by general low immunization rates. The emergence of avian influenza against the background of the scenario of a human influenza pandemic has revived public interest in the disease. According to the World Health Organisation, it is only the question on the beginning of a new influenza pandemic. The virus type of the new pandemic is still uncertain and it is also unclear, if a pandemic spread of the virus may be prevented by consistent controlling of avian influenza.

  6. [Humanized childbirth].

    Science.gov (United States)

    Kuo, Su-Chen

    2005-06-01

    Childbirth is a major event in a family. The expectant parent's perception of the childbirth experience influences his or her development as a parent. Making childbirth a positive and satisfying experience for women is the responsibility of health care providers. Women want to have physical and emotional privacy during labor and delivery, and to experience both in a friendly, comfortable environment. For women expected to undergo normal deliveries, humanized childbirth is one accessible approach. This article explores the definition and evolution of humanized childbirth and the care practice that it involves. It also explores birth plans and birth experiences, and the improvements necessary to routine labor practices to enable women to participate in decision making about their childbirth experiences. The author emphasizes that when health-care providers recognize the value of humanized childbirth and make changes accordingly, the dignity of women's childbirth experiences will be enhanced.

  7. Beyond Humanisms

    Directory of Open Access Journals (Sweden)

    Capurro, Rafael

    2012-01-01

    Full Text Available In the first part of this paper a short history of Western humanisms (Socrates, Pico della Mirandola, Descartes, Kant is presented. As far as these humanisms rest on a fixation of the ‘humanum’ they are metaphysical, although they might radically differ from each other. The second part deals with the present debate on trans- and posthumanism in the context of some breath-taking developments in science and technology.Angeletics, a theory of messengers and messages, intends to give an answer to the leading question of this paper, namely: ‘what does it mean to go beyond humanisms?’ The conclusion exposes briefly an ethics of hospitality and care from an angeletic perspective.

  8. 对氧磷酶1与多囊卵巢综合征的相关性研究%The Relationship between PON1 and Polycystic Ovary Syndrome

    Institute of Scientific and Technical Information of China (English)

    石溪

    2011-01-01

    对氧磷酶(PON)是一类能催化水解磷酸酯键的芳香酯酶,能够水解高密度脂蛋白和低密度脂蛋白分子中的氧化型磷脂,具有抗氧化作用.PON 活性异常与动脉粥样硬化发生密切相关,PON日益受到重视.随着临床和分子生物学的进展发现,PON的活性与多囊卵巢综合征及其并发症密切相关,但在国内尚未见报道.现就此研究进展作一综述.%Paraoxonase( PON )is a kind of aromatic esterase that can catalyze the hydrolysis of phosphate ester bond in high density lipoprotein and low density lipoprotein with antioxidant activity. Since a close relationship between PON activity and atherosclerosis was found,PON is receiving increasing attention. With the progress of clinical and molecular biology in recent years, foreign scholars have found that PON activity is closely related to polycystic ovary syndrome and its complications. However,no such report has been found in China. Here is to review related progress in this regard.

  9. Human Rights, Human Needs, Human Development, Human Security : Relationships between four international 'human' discourses

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    textabstractHuman rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each

  10. Nothing Human

    Science.gov (United States)

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  11. Human Trafficking

    Science.gov (United States)

    Wilson, David McKay

    2011-01-01

    The shadowy, criminal nature of human trafficking makes evaluating its nature and scope difficult. The U.S. State Department and anti-trafficking groups estimate that worldwide some 27 million people are caught in a form of forced servitude today. Public awareness of modern-day slavery is gaining momentum thanks to new abolitionist efforts. Among…

  12. Human waste

    NARCIS (Netherlands)

    Amin, Md Nurul; Kroeze, Carolien; Strokal, Maryna

    2017-01-01

    Many people practice open defecation in south Asia. As a result, lot of human waste containing nutrients such as nitrogen (N) and phosphorus (P) enter rivers. Rivers transport these nutrients to coastal waters, resulting in marine pollution. This source of nutrient pollution is, however, ignored in

  13. Nothing Human

    Science.gov (United States)

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  14. Practicing Humanities

    DEFF Research Database (Denmark)

    Gimmler, Antje

    2016-01-01

    and self-reflective democracy. Contemporary humanities have adopted a new orientation towards practices, and it is not clear how this fits with the ideals of ‘Bildung’ and ‘pure science’. A possible theoretical framework for this orientation towards practices could be found in John Dewey’s pragmatic...

  15. Human Rights in the Humanities

    Science.gov (United States)

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  16. Human Rights in the Humanities

    Science.gov (United States)

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  17. Digital Humanities

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørn

    2015-01-01

    Artiklen præsenterer først nogle generelle problemstillinger omkring Digital Humanities (DH) med det formål at undersøge dem nærmere i relation til konkrete eksempler på forskellige digitaliseringsmåder og ændringer i dokumentproduktion. I en nærmere afgrænsning vælger artiklen den tendens i DH...

  18. Human paleoneurology

    CERN Document Server

    2015-01-01

    The book presents an integrative review of paleoneurology, the study of endocranial morphology in fossil species. The main focus is on showing how computed methods can be used to support advances in evolutionary neuroanatomy, paleoanthropology and archaeology and how they have contributed to creating a completely new perspective in cognitive neuroscience. Moreover, thanks to its multidisciplinary approach, the book addresses students and researchers approaching human paleoneurology from different angles and for different purposes, such as biologists, physicians, anthropologists, archaeologists

  19. Digital Humanities

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørn

    2015-01-01

    Artiklen præsenterer først nogle generelle problemstillinger omkring Digital Humanities (DH) med det formål at undersøge dem nærmere i relation til konkrete eksempler på forskellige digitaliseringsmåder og ændringer i dokumentproduktion. I en nærmere afgrænsning vælger artiklen den tendens i DH...

  20. Human universe

    CERN Document Server

    Cox, Brian

    2014-01-01

    Human life is a staggeringly strange thing. On the surface of a ball of rock falling around a nuclear fireball in the blackness of a vacuum the laws of nature conspired to create a naked ape that can look up at the stars and wonder where it came from. What is a human being? Objectively, nothing of consequence. Particles of dust in an infinite arena, present for an instant in eternity. Clumps of atoms in a universe with more galaxies than people. And yet a human being is necessary for the question itself to exist, and the presence of a question in the universe - any question - is the most wonderful thing. Questions require minds, and minds bring meaning. What is meaning? I don't know, except that the universe and every pointless speck inside it means something to me. I am astonished by the existence of a single atom, and find my civilisation to be an outrageous imprint on reality. I don't understand it. Nobody does, but it makes me smile. This book asks questions about our origins, our destiny, and our place i...

  1. Human Capital, (Human) Capabilities and Higher Education

    Science.gov (United States)

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  2. Human Capital, (Human) Capabilities and Higher Education

    Science.gov (United States)

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  3. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  4. Human steroidogenesis

    DEFF Research Database (Denmark)

    Andersen, Claus Y; Ezcurra, Diego

    2014-01-01

    steroid concentrations cause alterations in endometrial development, affecting oocyte viability in assisted reproductive technology. Furthermore, it has been proposed that elevated progesterone levels have a negative effect on the reproductive outcome of COS. This may arise from an asynchrony between...... reviews current knowledge of the regulation of progesterone in the human ovary during the follicular phase and highlights areas where knowledge remains limited. In this review, we provide in-depth information outlining the regulation and function of gonadotropins in the complicated area of steroidogenesis...

  5. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  6. Human Toxocariasis

    Directory of Open Access Journals (Sweden)

    Mehmet Burak Selek

    2013-09-01

    Full Text Available Human toxocariasis is an parasitic infection caused by the ingestion of larvae of dog nematode Toxocara canis and less frequently of cat nematode T.cati. Toxocara eggs, shed to environment by infected dogs' and cats' droppings, become infective by embryonation. Humans, particularly children, can be infected by accidentally ingesting embryonated Toxocara eggs. Larvae hatch in the small intestine, penetrate the intestinal wall and migrate to other parts of body via the bloodstream. It is generally a benign, asymptomatic, and self-limiting disease, although migrating larvae can cause damage to tissues and organs, especially brain involvement can cause severe morbidity. The two main clinical presentations of toxocariasis are visceral larva migrans (VLM (a systemic disease caused by larval migration through major organs and ocular larva migrans (OLM (a disease limited to the eyes and optic nerves. There are also two less-severe syndromes which have recently been described, one mainly in children (covert toxocariasis and the other mainly in adults (common toxocariasis. Diagnosis is usually made by clinical signs/symptoms, epidemiological background of the patient and the use of immunological methods (ELISA or western-blot. On the other hand definitive diagnosis is much more challenging, since it requires the demonstration of larvae via biopsy or autopsy. Most cases of toxocariasis clear up without any treatment. VLM is primarily treated with antihelmintic drugs, such as; albendazole or mebendazole. Treatment of OLM is more difficult and usually consists of measures to prevent progressive damage to the eye like steroids. Laser photocoagulation and cryoretinopexy may also be used to treat severe cases. Since eradicating T.canis infection is difficult due to the complexity of its life cycle, prevention of toxocariasis is always preferred. Toxocara eggs have a strong protective layer which makes the eggs able to survive in the environment for months or

  7. NATO Human View Architecture and Human Networks

    Science.gov (United States)

    Handley, Holly A. H.; Houston, Nancy P.

    2010-01-01

    The NATO Human View is a system architectural viewpoint that focuses on the human as part of a system. Its purpose is to capture the human requirements and to inform on how the human impacts the system design. The viewpoint contains seven static models that include different aspects of the human element, such as roles, tasks, constraints, training and metrics. It also includes a Human Dynamics component to perform simulations of the human system under design. One of the static models, termed Human Networks, focuses on the human-to-human communication patterns that occur as a result of ad hoc or deliberate team formation, especially teams distributed across space and time. Parameters of human teams that effect system performance can be captured in this model. Human centered aspects of networks, such as differences in operational tempo (sense of urgency), priorities (common goal), and team history (knowledge of the other team members), can be incorporated. The information captured in the Human Network static model can then be included in the Human Dynamics component so that the impact of distributed teams is represented in the simulation. As the NATO militaries transform to a more networked force, the Human View architecture is an important tool that can be used to make recommendations on the proper mix of technological innovations and human interactions.

  8. [Human papillomaviruses].

    Science.gov (United States)

    Gross, G

    2003-10-01

    Human papillomaviruses (HPV) infect exclusively the basal cells of the skin and of mucosal epithelia adjacent to the skin such as the mouth, the upper respiratory tract, the lower genital tract and the anal canal. HPV does not lead to a viremia. Basically there are three different types of HPV infection: Clinically visible lesions, subclinical HPV infections and latent HPV infections. Distinct HPV types induce morphologically and prognostically different clinical pictures. The most common HPV associated benign tumor of the skin is the common wart. Infections of the urogenitoanal tract with specific HPV-types are recognised as the most frequent sexually transmitted viral infections. So-called "high-risk" HPV-types (HPV16, 18 and others) are regarded by the world health organisation as important risk-factors for the development of genital cancer (mainly cervical cancer), anal cancer and upper respiratory tract cancer in both genders. Antiviral substances with a specific anti-HPV effect are so far unknown. Conventional therapies of benign skin warts and of mucosal warts are mainly nonspecific. They comprise tissue-destroying therapies such as electrocautery, cryotherapy and laser. In addition cytotoxic substances such as podophyllotoxin and systemic therapy with retinoids are in use. Systemically and topically administered immunotherapies represent a new approach for treatment. Both interferons and particularly the recently developed imiquimod, an interferon-alpha and cytokine-inductor lead to better results and are better tolerated then conventional therapies. HPV-specific vaccines have been developed in the last 5 years and will be used in future for prevention and treatment of benign and malignant HPV-associated tumors of the genitoanal tract in both sexes.

  9. Human Development Report 1991: Financing Human Development

    OpenAIRE

    United Nations Development Programme, UNDP

    1991-01-01

    Lack of political commitment rather than financial resources is often the real barrier to human development. This is the main conclusion of Human Development Report 1991 - the second in a series of annual reports on the subject.

  10. The golden triangle of human dignity: human security, human development and human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2004-01-01

    The success or failure of processes of democratization cannot be detached from processes of development related to the aspirations of people at the grassroots. Human rights, in a more theoretical terminology, require human development in order to enhance human security.

  11. Human-machine interactions

    Science.gov (United States)

    Forsythe, J. Chris; Xavier, Patrick G.; Abbott, Robert G.; Brannon, Nathan G.; Bernard, Michael L.; Speed, Ann E.

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  12. Special Section: Human Rights

    Science.gov (United States)

    Frydenlund, Knut; And Others

    1978-01-01

    Eleven articles examine human rights in Europe. Topics include unemployment, human rights legislation, role of the Council of Europe in promoting human rights, labor unions, migrant workers, human dignity in industralized societies, and international violence. Journal available from Council of Europe, Directorate of Press and Information, 67006…

  13. Scalability of human models

    NARCIS (Netherlands)

    Rodarius, C.; Rooij, L. van; Lange, R. de

    2007-01-01

    The objective of this work was to create a scalable human occupant model that allows adaptation of human models with respect to size, weight and several mechanical parameters. Therefore, for the first time two scalable facet human models were developed in MADYMO. First, a scalable human male was

  14. Visualizing Humans by Computer.

    Science.gov (United States)

    Magnenat-Thalmann, Nadia

    1992-01-01

    Presents an overview of the problems and techniques involved in visualizing humans in a three-dimensional scene. Topics discussed include human shape modeling, including shape creation and deformation; human motion control, including facial animation and interaction with synthetic actors; and human rendering and clothing, including textures and…

  15. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation.

    Science.gov (United States)

    Aviram, Michael; Rosenblat, Mira; Gaitini, Diana; Nitecki, Samy; Hoffman, Aaron; Dornfeld, Leslie; Volkova, Nina; Presser, Dita; Attias, Judith; Liker, Harley; Hayek, Tony

    2004-06-01

    Dietary supplementation with polyphenolic antioxidants to animals was shown to be associated with inhibition of LDL oxidation and macrophage foam cell formation, and attenuation of atherosclerosis development. We investigated the effects of pomegranate juice (PJ, which contains potent tannins and anthocyanins) consumption by atherosclerotic patients with carotid artery stenosis (CAS) on the progression of carotid lesions and changes in oxidative stress and blood pressure. Ten patients were supplemented with PJ for 1 year and five of them continued for up to 3 years. Blood samples were collected before treatment and during PJ consumption. In the control group that did not consume PJ, common carotid intima-media thickness (IMT) increased by 9% during 1 year, whereas, PJ consumption resulted in a significant IMT reduction, by up to 30%, after 1 year. The patients' serum paraoxonase 1 (PON 1) activity was increased by 83%, whereas serum LDL basal oxidative state and LDL susceptibility to copper ion-induced oxidation were both significantly reduced, by 90% and 59%, respectively, after 12 months of PJ consumption, compared to values obtained before PJ consumption. Furthermore, serum levels of antibodies against oxidized LDL were decreased by 19%, and in parallel serum total antioxidant status (TAS) was increased by 130% after 1 year of PJ consumption. Systolic blood pressure was reduced after 1 year of PJ consumption by 12% [corrected] and was not further reduced along 3 years of PJ consumption. For all studied parameters, the maximal effects were observed after 1 year of PJ consumption. Further consumption of PJ, for up to 3 years, had no additional beneficial effects on IMT and serum PON1 activity, whereas serum lipid peroxidation was further reduced by up to 16% after 3 years of PJ consumption. The results of the present study thus suggest that PJ consumption by patients with CAS decreases carotid IMT and systolic blood pressure and these effects could be related to

  16. Atorvastatin and fenofibrate combination induces the predominance of the large HDL subclasses and increased apo AI fractional catabolic rates in New Zealand white rabbits with exogenous hypercholesterolemia.

    Science.gov (United States)

    Flores-Castillo, Cristobal; Zamora-Pérez, Juan Á; Carreón-Torres, Elizabeth; Arzola-Paniagua, Angélica; Aguilar-Salinas, Carlos; López-Olmos, Victoria; Fragoso, José M; Luna-Luna, María; Rodríguez-Pérez, José M; Franco, Martha; Vargas-Alarcón, Gilberto; Pérez-Méndez, Óscar

    2015-08-01

    The anti-atherogenic properties of high-density lipoproteins (HDLs) may be related to their structure and metabolism. The HDL physicochemical characteristics that determine their plasma clearance during treatment with statins and fibrates are not well understood. In this study, we analyzed HDL-apo AI fractional catabolic rates (FCRs), size distributions, and the lipid composition of the HDL subclasses in New Zealand white rabbits with exogenous dyslipidemia that received low doses of atorvastatin and fenofibrate. Hypercholesterolemia decreased only partially with the combination of both drugs. HDL size distribution shifted toward larger particles among the groups of rabbits that received atorvastatin, fenofibrate, or their combination, compared with both the control group and the dyslipidemic group. The HDL subclasses were significantly rich in cholesterol in each of the groups compared with controls. The structural changes noted in the HDL subclasses were not associated with impaired plasma paraoxonase-1 (PON1) activity. The groups receiving monotherapy and the drug combination group were all associated with a higher apo AI FCR value compared with both the dyslipidemic rabbits and the control group. In conclusion, the combination of atorvastatin and fenofibrate induced a more favorable HDL subclass profile than did the individual use of these drugs. Similarly, the apo AI FCR values were augmented in every group receiving drug treatment (either monotherapy or combination therapy) in the setting of hypercholesterolemia. The anti-atherogenic properties of HDLs, excluding their capacity to bind PON1, may be enhanced by the structural and metabolic modifications induced by the combination of atorvastatin and fenofibrate. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  17. The Dietary Supplement Protandim® Decreases Plasma Osteopontin and Improves Markers of Oxidative Stress in Muscular Dystrophy Mdx Mice

    Science.gov (United States)

    Qureshi, Muhammad Muddasir; McClure, Warren C.; Arevalo, Nicole L.; Rabon, Rick E.; Mohr, Benjamin; Bose, Swapan K.; McCord, Joe M.; Tseng, Brian S.

    2010-01-01

    Therapeutic options for Duchenne muscular dystrophy (DMD), the most common and lethal neuromuscular disorder in children, remain elusive. Oxidative damage is implicated as a pertinent factor involved in its pathogenesis. Protandim® is an over-the-counter supplement with the ability to induce antioxidant enzymes. In this study we investigated whether Protandim® provided benefit using surrogate markers and functional measures in the dystrophin-deficient (mdx)mouse model of DMD. Male 3-week-old mdx mice were randomized into two treatment groups: control (receiving standard rodent chow) and Protandim®-supplemented standard rodent chow. The diets were continued for 6-week and 6-month studies. The endpoints included the oxidative stress marker thiobarbituric acid-reactive substances (TBARS), plasma osteopontin (OPN), plasma paraoxonase (PON1) activity, H&E histology, gadolinium-enhanced magnetic resonance imaging (MRI) of leg muscle and motor functional measurements. The Protandim® chow diet in mdx mice for 6 months was safe and well tolerated. After 6 months of Protandim®, a 48% average decrease in plasma TBARS was seen; 0.92 nmol/mg protein in controls versus 0.48 nmol/mg protein in the Protandim® group (p = .006). At 6 months, plasma OPN was decreased by 57% (p = .001) in the Protandim®-treated mice. Protandim® increased the plasma antioxidant enzyme PON1 activity by 35% (p = .018). After 6 months, the mdx mice with Protandim® showed 38% less MRI signal abnormality (p = .07) than mice on control diet. In this 6-month mdx mouse study, Protandim® did not significantly alter motor function nor histological criteria. PMID:20740052

  18. The Dietary Supplement Protandim Decreases Plasma Osteopontin and Improves Markers of Oxidative Stress in Muscular Dystrophy Mdx Mice.

    Science.gov (United States)

    Qureshi, Muhammad Muddasir; McClure, Warren C; Arevalo, Nicole L; Rabon, Rick E; Mohr, Benjamin; Bose, Swapan K; McCord, Joe M; Tseng, Brian S

    2010-06-01

    Therapeutic options for Duchenne muscular dystrophy (DMD), the most common and lethal neuromuscular disorder in children, remain elusive. Oxidative damage is implicated as a pertinent factor involved in its pathogenesis. Protandim((R)) is an over-the-counter supplement with the ability to induce antioxidant enzymes. In this study we investigated whether Protandim((R)) provided benefit using surrogate markers and functional measures in the dystrophin-deficient (mdx)mouse model of DMD. Male 3-week-old mdx mice were randomized into two treatment groups: control (receiving standard rodent chow) and Protandim((R))-supplemented standard rodent chow. The diets were continued for 6-week and 6-month studies. The endpoints included the oxidative stress marker thiobarbituric acid-reactive substances (TBARS), plasma osteopontin (OPN), plasma paraoxonase (PON1) activity, H&E histology, gadolinium-enhanced magnetic resonance imaging (MRI) of leg muscle and motor functional measurements. The Protandim((R)) chow diet in mdx mice for 6 months was safe and well tolerated. After 6 months of Protandim((R)), a 48% average decrease in plasma TBARS was seen; 0.92 nmol/mg protein in controls versus 0.48 nmol/mg protein in the Protandim((R)) group (p = .006). At 6 months, plasma OPN was decreased by 57% (p = .001) in the Protandim((R))-treated mice. Protandim((R)) increased the plasma antioxidant enzyme PON1 activity by 35% (p = .018). After 6 months, the mdx mice with Protandim((R)) showed 38% less MRI signal abnormality (p = .07) than mice on control diet. In this 6-month mdx mouse study, Protandim((R)) did not significantly alter motor function nor histological criteria.

  19. Implication of low HDL-c levels in patients with average LDL-c levels: a focus on oxidized LDL, large HDL subpopulation, and adiponectin.

    Science.gov (United States)

    Mascarenhas-Melo, Filipa; Sereno, José; Teixeira-Lemos, Edite; Marado, Daniela; Palavra, Filipe; Pinto, Rui; Rocha-Pereira, Petronila; Teixeira, Frederico; Reis, Flávio

    2013-01-01

    To evaluate the impact of low levels of high density lipoprotein cholesterol (HDL-c) on patients with LDL-c average levels, focusing on oxidative, lipidic, and inflammatory profiles. Patients with cardiovascular risk factors (n = 169) and control subjects (n = 73) were divided into 2 subgroups, one of normal HDL-c and the other of low HDL-c levels. The following data was analyzed: BP, BMI, waist circumference and serum glucose Total-c, TGs, LDL-c, oxidized LDL, total HDL-c and subpopulations (small, intermediate, and large), paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF- α , adiponectin, VEGF, and iCAM1. In the control subgroup with low HDL-c levels, significantly higher values of BP and TGs and lower values of PON1 activity and adiponectin were found, versus control normal HDL-c subgroup. However, differences in patients' subgroups were clearly more pronounced. Indeed, low HDL-c subgroup presented increased HbA1c, TGs, non-HDL-c, Ox-LDL, hsCRP, VEGF, and small HDL-c and reduced adiponectin and large HDL. In addition, Ox-LDL, large-HDL-c, and adiponectin presented interesting correlations with classical and nonclassical markers, mainly in the normal HDL-c patients' subgroup. In conclusion, despite LDL-c average levels, low HDL-c concentrations seem to be associated with a poor cardiometabolic profile in a population with cardiovascular risk factors, which is better evidenced by traditional and nontraditional CV biomarkers, including Ox-LDL, large HDL-c, and adiponectin.

  20. Clinical implications of sleep disordered breathing in acute myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Doron Aronson

    Full Text Available BACKGROUND: Sleep disordered breathing (SDB, characterized by nightly intermittent hypoxia, is associated with multiple pathophysiologic alterations that may adversely affect patients with acute myocardial infarction (AMI. This prospective study investigated whether the metabolic perturbations associated with SDB are present when these patients develop AMI and if they affect clinical outcomes. METHODS: We prospectively enrolled 180 AMI patients. SDB was defined as oxygen desaturation index (ODI >5 events/hour based on a Watch Pat-100 sleep study. Blood samples were obtained for high-sensitivity C-reactive protein (hs-CRP and markers of oxidative stress (lipid peroxides [PD] and serum paraoxonase-1 [PON-1] (arylesterase activity. Echocardiography was performed to evaluate cardiac dimensions and pulmonary artery systolic pressure. RESULTS: SDB was present in 116 (64% patients. Hs-CRP levels, PD and PON-1 were similar in patients with and without SDB. Echocardiography revealed higher left atrial dimension (4.1 ± 0.5 vs 3.8 ± 0.5 cm; P = 0.003 and a significant positive correlation between ODI and pulmonary artery systolic pressure (r = 0.41, P<0.0001. After a median follow up of 68 months, no significant differences were observed between the study groups with regard to clinical outcomes, including death, heart failure, myocardial infarction and unstable angina. CONCLUSION: There is a high prevalence of previously undiagnosed SDB among patients with AMI. SDB in the setting of AMI is associated with higher pulmonary artery systolic pressure. SDB was not associated with adverse clinical outcomes.

  1. The Human/Machine Humanities: A Proposal

    Directory of Open Access Journals (Sweden)

    Ollivier Dyens

    2016-03-01

    Full Text Available What does it mean to be human in the 21st century? The pull of engineering on every aspect of our lives, the impact of machines on how we represent ourselves, the influence of computers on our understanding of free-will, individuality and species, and the effect of microorganisms on our behaviour are so great that one cannot discourse on humanity and humanities without considering their entanglement with technology and with the multiple new dimensions of reality that it opens up. The future of humanities should take into account AI, bacteria, software, viruses (both organic and inorganic, hardware, machine language, parasites, big data, monitors, pixels, swarms systems and the Internet. One cannot think of humanity and humanities as distinct from technology anymore.

  2. From Human Past to Human Future

    OpenAIRE

    Robert G. Bednarik

    2013-01-01

    This paper begins with a refutation of the orthodox model of final Pleistocene human evolution, presenting an alternative, better supported account of this crucial phase. According to this version, the transition from robust to gracile humans during that period is attributable to selective breeding rather than natural selection, rendered possible by the exponential rise of culturally guided volitional choices. The rapid human neotenization coincides with the development of numerous somatic an...

  3. ISS Payload Human Factors

    Science.gov (United States)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  4. Has Human Evolution Stopped?

    OpenAIRE

    TEMPLETON, Alan R

    2010-01-01

    It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important ...

  5. Preference for human eyes in human infants.

    Science.gov (United States)

    Dupierrix, Eve; de Boisferon, Anne Hillairet; Méary, David; Lee, Kang; Quinn, Paul C; Di Giorgio, Elisa; Simion, Francesca; Tomonaga, Masaki; Pascalis, Olivier

    2014-07-01

    Despite evidence supporting an early attraction to human faces, the nature of the face representation in neonates and its development during the first year after birth remain poorly understood. One suggestion is that an early preference for human faces reflects an attraction toward human eyes because human eyes are distinctive compared with other animals. In accord with this proposal, prior empirical studies have demonstrated the importance of the eye region in face processing in adults and infants. However, an attraction for the human eye has never been shown directly in infants. The current study aimed to investigate whether an attraction for human eyes would be present in newborns and older infants. With the use of a preferential looking time paradigm, newborns and 3-, 6-, 9-, and 12-month-olds were simultaneously presented with a pair of nonhuman primate faces (chimpanzees and Barbary macaques) that differed only by the eyes, thereby pairing a face with original nonhuman primate eyes with the same face in which the eyes were replaced by human eyes. Our results revealed that no preference was observed in newborns, but a preference for nonhuman primate faces with human eyes emerged from 3months of age and remained stable thereafter. The findings are discussed in terms of how a preference for human eyes may emerge during the first few months after birth.

  6. Economics of human trafficking.

    Science.gov (United States)

    Wheaton, Elizabeth M; Schauer, Edward J; Galli, Thomas V

    2010-01-01

    Because freedom of choice and economic gain are at the heart of productivity, human trafficking impedes national and international economic growth. Within the next 10 years, crime experts expect human trafficking to surpass drug and arms trafficking in its incidence, cost to human well-being, and profitability to criminals (Schauer and Wheaton, 2006: 164-165). The loss of agency from human trafficking as well as from modern slavery is the result of human vulnerability (Bales, 2000: 15). As people become vulnerable to exploitation and businesses continually seek the lowest-cost labour sources, trafficking human beings generates profit and a market for human trafficking is created. This paper presents an economic model of human trafficking that encompasses all known economic factors that affect human trafficking both across and within national borders. We envision human trafficking as a monopolistically competitive industry in which traffickers act as intermediaries between vulnerable individuals and employers by supplying differentiated products to employers. In the human trafficking market, the consumers are employers of trafficked labour and the products are human beings. Using a rational-choice framework of human trafficking we explain the social situations that shape relocation and working decisions of vulnerable populations leading to human trafficking, the impetus for being a trafficker, and the decisions by employers of trafficked individuals. The goal of this paper is to provide a common ground upon which policymakers and researchers can collaborate to decrease the incidence of trafficking in humans.

  7. Effect of simvastatin on anti-oxidation and anti-inflammation properties of HDL in apoE-/-mice

    Directory of Open Access Journals (Sweden)

    Di TIAN

    2013-03-01

    Full Text Available Objectives  To investigate the effect of simvastatin on anti-oxidation and anti-inflammation properties of high density lipoprotein (HDL in apoE-/-mice fed with high-fat diet. Methods  Eighteen 8-week old male C57BL/6J mice as blank control group were fed with normal diet, and thirty 8-week old male apoE-/-mice were fed with high-fat diet. Four weeks later, 6 mice in each group were sacrificed. The remaining 24 apoE-/-mice were randomly divided into two groups (12 each: atherosclerosis group (AS group and simvastatin group, while the remaining 12 C57BL/6J mice served as control group. The mice in both control and AS group were fed with the original diet, and the mice in simvastatin group were fed with the same high-fat diet plus simvastatin 5mg/ (kg.d. At the end of the 8th and 16th week, 6 mice were sacrificed in each group. Serum lipid levels, paraoxonase 1 (PON1 activity (arylesterase activity, serum myeloperoxidase (MPO activity, high-density lipoprotein inflammation index (HII and serum hs-CRP levels were determined. The atherosclerotic lesion formation in the aorta was manifested by oil red O staining. Results  At the end of the 8th week, no difference was found in the levels of serum low density lipoprotein cholesterol (LDL-C and high density lipoprotein cholesterol (HDL-C between simvastatin and AS group. At the end of 16th week, the levels of serum LDL-C decreased significantly (P<0.01 and HDL-C increased significantly (P<0.05 in simvastatin group compared with AS group. At the end of the 8th and 16th week, a significant enhancement of the serum PON1 activity but marked decrease in MPO activity, HII, and serum hs-CRP levels were found in simvastatin group compared with that in AS group. The percentage of plaque area (surface area of plaque/ surface area of whole intima in the aorta was significantly smaller in simvastatin group than that in AS group (P<0.05 or P<0.01. Conclusions In addition to lowering LDL-C and elevating HDL

  8. Cerebrolysin protects against rotenone-induced oxidative stress and neurodegeneration

    Directory of Open Access Journals (Sweden)

    Abdel-Salam OME

    2014-05-01

    Full Text Available Omar ME Abdel-Salam,1 Nadia A Mohammed,2 Eman R Youness,2 Yasser A Khadrawy,3 Enayat A Omara,4 Amany A Sleem51Department of Toxicology and Narcotics, 2Department of Medical Biochemistry, 3Department of Physiology, 4Department of Pathology, 5Department of Pharmacology, National Research Centre, Dokki, Cairo, EgyptAbstract: We investigated the effect of cerebrolysin, a peptide mixture used for promoting memory and recovery from cerebral stroke, on the development of oxidative stress and nigrostriatal cell injury induced by rotenone administration in rats. Rotenone 1.5 mg/kg was given subcutaneously three times weekly either alone or in combination with cerebrolysin at 21.5, 43, or 86 mg/kg. Rats were euthanized 14 days after starting the rotenone injection. Lipid peroxidation (malondialdehyde, reduced glutathione (GSH, nitric oxide (nitrite concentrations, paraoxonase 1 (PON1, and acetylcholinesterase (AChE activities – as well as the monocyte chemoattractant protein-1 (MCP-1 and the antiapoptotic protein Bcl-2 – were measured in the brain. Histopathology, tyrosine hydroxylase, inducible nitric oxide synthase (iNOS, tumor necrosis factor-α (TNF-α, and cleaved caspase-3 immunohistochemistry were also performed. Rotenone caused a significantly elevated oxidative stress and proinflammatory response in the different brain regions. Malondialdehyde and nitric oxide concentrations were significantly increased, while GSH markedly decreased in the cerebral cortex, striatum, hippocampus, and in the rest of the brain. PON1 and AChE activities significantly decreased with respect to the control levels after rotenone application. Striatal Bcl-2 was significantly decreased while MCP-1 increased following rotenone injection. Rotenone caused prominent iNOS, TNF-α, and caspase-3 immunostaining in the striatum and resulted in markedly decreased tyrosine hydroxylase immunoreactivity in the substantia nigra and striatum. Cerebrolysin coadministered with

  9. Biochemical Study of Oxidative Stress Markers in the Liver, Kidney and Heart of High Fat Diet Induced Obesity in Rats

    Directory of Open Access Journals (Sweden)

    Noeman Saad A

    2011-08-01

    Full Text Available Abstract Background Obesity has become a leading global health problem owing to its strong association with a high incidence of diseases. Aim To induce rat obesity using high fat diet (HFD and to estimate oxidative stress markers in their liver, heart and kidney tissues in order to shed the light on the effect of obesity on these organs. Materials and methods Sixty white albino rats weighing 150-200 g were randomly divided into two equal groups; group I: received high fat diet for 16 weeks, and group II (control group: received only normal diet (rat chow for 16 weeks. Blood samples were taken for measurement of lipid profile, tissue samples from liver, heart and kidney were taken for determination of malondialdehyde (MDA, protein carbonyl (PCO, reduced glutathione (GSH levels, and the activities of glutathione S- transferase (GST glutathione peroxidase (GPx, catalase (CAT and paraoxonase1 (PON1 enzymes. Results Data showed that feeding HFD diet significantly increased final body weight and induced a state of dyslipideamia. Also our results showed a significant increase MDA and PCO levels in the hepatic, heart and renal tissues of obese rats, as well as a significant decrease in the activity of GST, GPx and PON 1 enzymes. On the other hand CAT enzyme activity showed significant decrease only in renal tissues of obese rats with non significant difference in hepatic and heart tissues. GSH levels showed significant decrease in both renal and hepatic tissues of obese animals and significant increase in their heart tissues. Correlation studies in obese animals showed a negative correlation between MDA and PCO tissue levels and the activities of GPx, GST and PON1 in all tissues and also with CAT enzyme activity in renal tissues. Also a negative correlation was detected between MDA & PCO tissues levels and GSH levels in both hepatic and renal tissues. While positive correlation was found between them and GSH levels in heart tissues. Conclusion High fat

  10. Human assisted robotic exploration

    Science.gov (United States)

    Files, B. T.; Canady, J.; Warnell, G.; Stump, E.; Nothwang, W. D.; Marathe, A. R.

    2016-05-01

    In support of achieving better performance on autonomous mapping and exploration tasks by incorporating human input, we seek here to first characterize humans' ability to recognize locations from limited visual information. Such a characterization is critical to the design of a human-in-the-loop system faced with deciding whether and when human input is useful. In this work, we develop a novel and practical place-recognition task that presents humans with video clips captured by a navigating ground robot. Using this task, we find experimentally that human performance does not seem to depend on factors such as clip length or familiarity with the scene and also that there is significant variability across subjects. Moreover, we find that humans significantly outperform a state-of-the-art computational solution to this problem, suggesting the utility of incorporating human input in autonomous mapping and exploration techniques.

  11. Human Use Index (Future)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  12. Human Papillomavirus (HPV) Vaccines

    Science.gov (United States)

    ... Directory Cancer Prevention Overview Research Human Papillomavirus (HPV) Vaccines On This Page What are human papillomaviruses? Which ... infections? Can HPV infections be prevented? What HPV vaccines are available? Who should get the HPV vaccines? ...

  13. Human Use Index

    Data.gov (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  14. Telling the Human Story.

    Science.gov (United States)

    Richardson, Miles

    1987-01-01

    Proposes that one of the fundamental human attributes is telling stories. Explores the debate on whether Neanderthals possessed language ability. Discusses the role of the "human story" in teaching anthropology. (DH)

  15. Human Services Offices

    Data.gov (United States)

    Fairfax County, Virginia — This data contains point features representing the human services offices within Fairfax County.“HS_Region” is the office for each human services region, “DFS_Area”...

  16. Human Resource Accounting System

    Science.gov (United States)

    Cerullo, Michael J.

    1974-01-01

    Main objectives of human resource accounting systems are to satisfy the informational demands made by investors and by operating managers. The paper's main concern is with the internal uses of a human asset system. (Author)

  17. The Growing Human Population.

    Science.gov (United States)

    Keyfitz, Nathan

    1989-01-01

    Discusses the issue of human population. Illustrates the projections of the growing human population in terms of developed and less developed countries. Describes the family planning programs in several countries. Lists three references for further reading. (YP)

  18. Human bites (image)

    Science.gov (United States)

    Human bites present a high risk of infection. Besides the bacteria which can cause infection, there is ... the wound extends below the skin. Anytime a human bite has broken the skin, seek medical attention.

  19. Monogenic human obesity syndromes

    National Research Council Canada - National Science Library

    Farooqi, I S; O'Rahilly, S

    2004-01-01

    .... This chapter will consider the human monogenic obesity syndromes that have been characterized to date and discuss how far such observations support the physiological role of these molecules in the regulation of human body weight and neuroendocrine function.

  20. Skin and the non-human human

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2013-01-01

    The article puts forward an aesthetic and psychoanalytic analysis of Titian's painting, The Flaying of Marsyas, arguing that the painting is a reflection on the human subject as a being constituted by skin and by a core of non-humanity. The analysis is partly an answer to Melanie Hart's (2007......) article 'Visualizing the mind: Looking at Titian's Flaying of Marsyas', addressing features of the painting not commented on by Hart, and supplementing Hart's (Kleinian) theoretical frame by involving Didier Anzieu's 'skin ego', Slavoj Zizek's concept of the 'non-human', Giorgio Agamben's term...

  1. Human productivity program definition

    Science.gov (United States)

    Cramer, D. B.

    1985-01-01

    The optimization of human productivity on the space station within the existing resources and operational constraints is the aim of the Human Productivity Program. The conceptual objectives of the program are as follows: (1) to identify long lead technology; (2) to identify responsibility for work elements; (3) to coordinate the development of crew facilities and activities; and (4) to lay the foundation for a cost effective approach to improving human productivity. Human productivity work elements are also described and examples are presented.

  2. Human Resource Management System

    OpenAIRE

    Navaz, A. S. Syed; Fiaz, A. S. Syed; Prabhadevi, C.; V.Sangeetha; Gopalakrishnan,S.

    2013-01-01

    The paper titled HUMAN RESOURCE MANAGEMENT SYSTEM is basically concerned with managing the Administrator of HUMAN RESOURCE Department in a company. A Human Resource Management System, refers to the systems and processes at the intersection between human resource management and information technology. It merges HRM as a discipline and in particular its basic HR activities and processes with the information technology field, whereas the programming of data processing systems evolved into standa...

  3. Human nature and enhancement.

    Science.gov (United States)

    Buchanan, Allen

    2009-03-01

    Appeals to the idea of human nature are frequent in the voluminous literature on the ethics of enhancing human beings through biotechnology. Two chief concerns about the impact of enhancements on human nature have been voiced. The first is that enhancement may alter or destroy human nature. The second is that if enhancement alters or destroys human nature, this will undercut our ability to ascertain the good because, for us, the good is determined by our nature. The first concern assumes that altering or destroying human nature is in itself a bad thing. The second concern assumes that human nature provides a standard without which we cannot make coherent, defensible judgments about what is good. I will argue (1) that there is nothing wrong, per se, with altering or destroying human nature, because, on a plausible understanding of what human nature is, it contains bad as well as good characteristics and there is no reason to believe that eliminating some of the bad would so imperil the good as to make the elimination of the bad impermissible, and (2) that altering or destroying human nature need not result in the loss of our ability to make judgments about the good, because we possess a conception of the good by which we can and do evaluate human nature. I will argue that appeals to human nature tend to obscure rather than illuminate the debate over the ethics of enhancement and can be eliminated in favor of more cogent considerations.

  4. Human Document Project

    NARCIS (Netherlands)

    Vries, de J.; Abelmann, L.; Manz, A.; Elwenspoek, M.C.

    2012-01-01

    “The Human Document Project” is a project which tries to answer all of the questions related to preserving information about the human race for tens of generations of humans to come or maybe even for a future intelligence which can emerge in the coming thousands of years. This document mainly focuss

  5. Has Human Evolution Stopped?

    Directory of Open Access Journals (Sweden)

    Alan R. Templeton

    2010-07-01

    Full Text Available It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  6. Has human evolution stopped?

    Science.gov (United States)

    Templeton, Alan R

    2010-07-01

    It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  7. (Human) Resourcing For CI

    DEFF Research Database (Denmark)

    Jørgensen, Frances; S., Jacob; Kofoed, Lise Busk

    2005-01-01

    More and more, the ability to compete in today’s market is viewed as being dependent on human capital. One of the most challenging aspects of human resource management involves supplying the organization with the human capital necessary to fulfill its objectives. This task becomes especially...

  8. Human Machine Learning Symbiosis

    Science.gov (United States)

    Walsh, Kenneth R.; Hoque, Md Tamjidul; Williams, Kim H.

    2017-01-01

    Human Machine Learning Symbiosis is a cooperative system where both the human learner and the machine learner learn from each other to create an effective and efficient learning environment adapted to the needs of the human learner. Such a system can be used in online learning modules so that the modules adapt to each learner's learning state both…

  9. Monogenic human obesity.

    Science.gov (United States)

    Farooqi, I Sadaf

    2008-01-01

    We and others have identified several single gene defects that disrupt the molecules in the leptinmelanocortin pathway causing severe obesity in humans. In this review, we consider these human monogenic obesity syndromes and discuss how far the characterisation of these patients has informed our understanding of the physiological role of leptin and the melanocortins in the regulation of human body weight and neuroendocrine function.

  10. Investigation of Evolved Paraoxonase-1 Variants for Prevention of Organophosphorous Pesticide Compound Intoxication

    Science.gov (United States)

    2014-04-04

    were determined by Michaelis - Menten steady state kinetics using Prism Graphpad (Irvine, CA). Kinetic data for CMP hydrolysis was used as a metric to...against CMP, paraoxon and phenyl acetate versus G3C9 expression in E. coli (Table 1). A closer examination of the Michaelis - Menten parameters reveals...0.05% BSA 1.09 ± 0.06 45 ± 9 24 ± 5 Table 2. Michaelis - Menten parameters for G3C9 CMP hydrolysis. G3C9 expressed in mammalian cells displayed

  11. Maintenance of Paraoxonase 2 Activity as a Strategy to Attenuate P. Aeruginosa Virulence

    Science.gov (United States)

    2014-10-01

    anesthetized mice were filled through the trachea with 2 ml of 500 µM of 3OC12 in the micellar solution and left for 1 hour before harvesting. Control...factor-induced release of endogenous fatty acids analyzed by a highly sensitive high-performance liquid chromatography method. J. Lipid Res. 38, 1913-1922...S. (2000) A novel and sensitive method for the quantification of N-3-oxoacyl homoserine lactones using gas chromatography -mass spectrometry

  12. Maintenance of Paraoxonase 2 Activity as a Strategy to Attenuate P. Aeruginosa Virulence

    Science.gov (United States)

    2013-10-01

    µM 3OC12 (previously shown to inactivate > 90% of PON2 activity) and PON2 immunoprecipitated (IP). The IP PON2 was run on an SDS- PAGE gel and the...protein coupled taste receptor T2R38 in sinonasal epithelial cells, mediating direct antibacterial effects(10). These diverse responses suggest that

  13. Preparative Production of Acetylcholinesterase and Paraoxonase in Procaryotic and Eucaryotic Expression in Systems

    Science.gov (United States)

    2006-01-01

    agar and screened with the target substrate. Positive colonies (as determined by the appearance of a colored or fluorescent product) were transferred...natural amino acids, with the exception of L-methionine, 40µg/ml of seleno-L-methionine, 1µg/ml of vitamins ( Riboflavin , Niacinamide, Pyridoxine

  14. From Human Past to Human Future

    Directory of Open Access Journals (Sweden)

    Robert G. Bednarik

    2013-01-01

    Full Text Available This paper begins with a refutation of the orthodox model of final Pleistocene human evolution, presenting an alternative, better supported account of this crucial phase. According to this version, the transition from robust to gracile humans during that period is attributable to selective breeding rather than natural selection, rendered possible by the exponential rise of culturally guided volitional choices. The rapid human neotenization coincides with the development of numerous somatic and neural detriments and pathologies. Uniformitarian reasoning based on ontogenic homology suggests that the cognitive abilities of hominins are consistently underrated in the unstable orthodoxies of Pleistocene archaeology. A scientifically guided review establishes developmental trajectories defining recent changes in the human genome and its expressions, which then form the basis of attempts to extrapolate from them into the future. It is suggested that continuing and perhaps accelerating unfavorable genetic changes to the human species, rather than existential threats such as massive disasters, pandemics, or astrophysical events, may become the ultimate peril of humanity.

  15. Humanity at the Edge

    DEFF Research Database (Denmark)

    Svendsen, Mette N.; Gjødsbøl, Iben M.; Dam, Mie S.

    2017-01-01

    At the heart of anthropology and the social sciences lies a notion of human existence according to which humans and animals share the basic need for food, but only humans have the capacity for morality. Based on fieldwork in a pig laboratory, a neonatal intensive care unit (NICU), and a dementia ...... human and animal value and agency with approaches that focus on human experience and virtue ethics, we argue that ‘the human’ at stake in the moral laboratory of feeding precarious lives puts ‘the human’ in anthropology at disposal for moral experimentation....

  16. Jordan Adjusted Human Development

    OpenAIRE

    Ababsa, Myriam

    2014-01-01

    Jordan Human Development Index (HDI) and Adjusted Human Development Index (IHDI) In 1990, the United Nations Development Programme designed a Human Development Index composed of life expectancy at birth, level of education and gross domestic product (GDP) per capita. In 2011, the UNDP ranked Jordan 95th out of 187 countries with a human development index of 0.698, up from 0.591 in 1990, making it the leading medium-range country for human development (fig. VIII.1). In 2010, the inequality adj...

  17. Human Beings And Water

    OpenAIRE

    2016-01-01

    The writer of this paper on this writing is talking about the human beings and water. Water is one of the very fundamentally things that human beings need to keep their lives. Human beings sometimes do not realise that the water is very important for them because they actually cannot live their lives without the present of water. Human beings can keep their lives without rice, but cannot without water. For instances the use of water for human beings are domestic use, cooking, washing, bathing...

  18. Human rights and bioethics.

    Science.gov (United States)

    Barilan, Y M; Brusa, M

    2008-05-01

    In the first part of this article we survey the concept of human rights from a philosophical perspective and especially in relation to the "right to healthcare". It is argued that regardless of meta-ethical debates on the nature of rights, the ethos and language of moral deliberation associated with human rights is indispensable to any ethics that places the victim and the sufferer in its centre. In the second part we discuss the rise of the "right to privacy", particularly in the USA, as an attempt to make the element of personal free will dominate over the element of basic human interest within the structure of rights and when different rights seem to conflict. We conclude by discussing the relationship of human rights with moral values beyond the realm of rights, mainly human dignity, free will, human rationality and response to basic human needs.

  19. Human Milk Banking.

    Science.gov (United States)

    Haiden, Nadja; Ziegler, Ekhard E

    2016-01-01

    Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula.

  20. Human Capital and Sustainability

    Directory of Open Access Journals (Sweden)

    Garry Jacobs

    2011-01-01

    Full Text Available A study of sustainability needs to consider the role of all forms of capital—natural, biological, social, technological, financial, cultural—and the complex ways in which they interact. All forms of capital derive their value, utility and application from human mental awareness, creativity and social innovation. This makes human capital, including social capital, the central determinant of resource productivity and sustainability. Humanity has entered the Anthropocene Epoch in which human changes have become the predominant factor in evolution. Humanity is itself evolving from animal physicality to social vitality to mental individuality. This transition has profound bearing on human productive capabilities, adaptability, creativity and values, the organization of economy, public policy, social awareness and life styles that determine sustainability. This article examines the linkages between population, economic development, employment, education, health, social equity, cultural values, energy intensity and sustainability in the context of evolving human consciousness. It concludes that development of human capital is the critical determinant of long-term sustainability and that efforts to accelerate the evolution of human consciousness and emergence of mentally self-conscious individuals will be the most effective approach for ensuring a sustainable future. Education is the primary lever. Human choice matters.

  1. Integrated Environmental Modelling: human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  2. Human organ markets and inherent human dignity.

    Science.gov (United States)

    MacKellar, Calum

    2014-01-01

    It has been suggested that human organs should be bought and sold on a regulated market as any other material property belongingto an individual. This would have the advantage of both addressing the grave shortage of organs available for transplantation and respecting the freedom of individuals to choose to do whatever they want with their body parts. The old arguments against such a market in human organs are, therefore, being brought back into question. The article examines the different arguments both in favour and against the sale of human organs. It concludes that the body and any of its elements is a full expression of the whole person. As such, they cannot have a price if the individual is to retain his or her full inherent dignity and if society is to retain and protect this very important concept.

  3. Chimeras and human dignity.

    Science.gov (United States)

    de Melo-Martín, Inmaculada

    2008-12-01

    Discussions about whether new biomedical technologies threaten or violate human dignity are now common. Indeed, appeals to human dignity have played a central role in national and international debates about whether to allow particular kinds of biomedical investigations. The focus of this paper is on chimera research. I argue here that both those who claim that particular types of human-nonhuman chimera research threaten human dignity and those who argue that such threat does not exist fail to make their case. I first introduce some of the arguments that have been offered supporting the claim that the creation of certain sorts of chimeras threatens or violates human dignity. I next present opponents' assessments of such arguments. Finally I critically analyze both the critics' and the supporters' claims about whether chimera research threatens human dignity.

  4. Human Performance in Space

    Science.gov (United States)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    Human factors is a critical discipline for human spaceflight. Nearly every human factors research area is relevant to space exploration -- from the ergonomics of hand tools used by astronauts, to the displays and controls of a spacecraft cockpit or mission control workstation, to levels of automation designed into rovers on Mars, to organizational issues of communication between crew and ground. This chapter focuses more on the ways in which the space environment (especially altered gravity and the isolated and confined nature of long-duration spaceflight) affects crew performance, and thus has specific novel implications for human factors research and practice. We focus on four aspects of human performance: neurovestibular integration, motor control and musculo-skeletal effects, cognitive effects, and behavioral health. We also provide a sampler of recent human factors studies from NASA.

  5. Developing human technology curriculum

    Directory of Open Access Journals (Sweden)

    Teija Vainio

    2012-10-01

    Full Text Available During the past ten years expertise in human-computer interaction has shifted from humans interacting with desktop computers to individual human beings or groups of human beings interacting with embedded or mobile technology. Thus, humans are not only interacting with computers but with technology. Obviously, this shift should be reflected in how we educate human-technology interaction (HTI experts today and in the future. We tackle this educational challenge first by analysing current Master’s-level education in collaboration with two universities and second, discussing postgraduate education in the international context. As a result, we identified core studies that should be included in the HTI curriculum. Furthermore, we discuss some practical challenges and new directions for international HTI education.

  6. Humanities, Digital Humanities, Media studies, Internet studies

    DEFF Research Database (Denmark)

    Brügger, Niels

    the interplay between four areas which until now to a certain extent have been separated: Traditional Hu- manities, Digital Humanities, Media studies, and Internet studies. The vision is followed by an outline of how it can be unfolded in concrete activities, in the form of research projects, research......Todays expanding digital landscape constitutes an important research object as well as the research environment for the Humanities at the beginning of the 21st century. Taking this state of affairs as a starting point this inaugural lecture presents a vision for how the digital affects...

  7. Advancing Human Rights

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The National Human Rights Action Plan of China (2012-2015) was initiated after the successful conclusion of the National Human Rights Action Plan of China (2009-2010).The Chinese government in late July published an assessment report on the implementation of the plan,elaborating on the full implementation of China's first-ever national program on human rights development,which was drafted in April 2009.

  8. Human hemoglobin genetics

    Energy Technology Data Exchange (ETDEWEB)

    Honig, G.R.; Adams, J.G.

    1986-01-01

    This book contains the following 10 chapters: Introduction; The Human Hemoglobins; The Human Globin Genes; Hemoglobin Synthesis and Globin Gene Expression; The Globin Gene Mutations - A. Mechanisms and Classification; The Globin Gene Mutations - B. Their Phenotypes and Clinical Expression; The Genetics of the Human Globin Gene Loci: Formal Genetics and Gene Linkage; The Geographic Distribution of Globin Gene Variation; Labortory Identification, Screening, Education, and Counseling for Abnormal Hemoglobins and Thalassemias; and Approaches to the Treatment of the Hemoglobin Disorders.

  9. Modern Human Capital Management

    OpenAIRE

    Feldberger, Madita

    2008-01-01

    Title: Modern Human Capital Management Seminar date: 30th of May 2008 Course: Master thesis in Business Administration, 15 ECTS Authors: Madita Feldberger Supervisor: Lars Svensson Keywords: Human capital, SWOT Analysis, Strategic Map, Balanced Scorecard Research Problem: Despite of the success of Human Capital Management (HCM) in research it did not arrive yet in the HR departments of many companies. Numerous firms even have problems to set their strategic goals with focus on HR. The HR Bala...

  10. Robotics for Human Exploration

    Science.gov (United States)

    Fong, Terrence; Deans, Mathew; Bualat, Maria

    2013-01-01

    Robots can do a variety of work to increase the productivity of human explorers. Robots can perform tasks that are tedious, highly repetitive or long-duration. Robots can perform precursor tasks, such as reconnaissance, which help prepare for future human activity. Robots can work in support of astronauts, assisting or performing tasks in parallel. Robots can also perform "follow-up" work, completing tasks designated or started by humans. In this paper, we summarize the development and testing of robots designed to improve future human exploration of space.

  11. [Human physiology: kidney].

    Science.gov (United States)

    Natochin, Iu V

    2010-01-01

    The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

  12. Human Performance Research Center

    Data.gov (United States)

    Federal Laboratory Consortium — Biochemistry:Improvements in energy metabolism, muscular strength and endurance capacity have a basis in biochemical and molecular adaptations within the human body....

  13. Extraterritorial Human Rights Obligations

    DEFF Research Database (Denmark)

    Amsinck Boie, Hans Nikolaj; Torp, Kristian

    adequately be addressed without including the approach to the problem taken in practice; Corporate Social Responsibility, CSR. The book therefore draws upon the concept of CSR and the approaches developed here and discusses whether states may utilize the CSR-based concept of human rights due diligence...... to fulfil their possible obligations to protect against human rights violations by corporations.......The book addresses the issue of corporate respect for human rights by examining if and how states are obligated to ensure that corporations originating from their jurisdiction respect human rights when they operate abroad. The existence of such a duty is much debated by academics at national...

  14. The psychology of humanness.

    Science.gov (United States)

    Haslam, Nick; Loughnan, Steve; Holland, Elise

    2013-01-01

    This chapter explores the ways in which the concept of "humanness" illuminates a wide and fascinating variety of psychological phenomena. After introducing the concept--everyday understandings of what it is to be human--we present a model of the diverse ways in which humanness can be denied to people. According to this model people may be perceived as lacking uniquely human characteristics, and thus likened to animals, or as lacking human nature, and thus likened to inanimate objects. Both of these forms of dehumanization occur with varying degrees of subtlety, from the explicit uses of derogatory animal metaphors, to stereotypes that ascribe lesser humanness or simpler minds to particular groups, to nonconscious associations between certain humans and nonhumans. After reviewing research on dehumanization through the lens of our model we examine additional topics that the psychology of humanness clarifies, notably the perception of nonhuman animals and the objectification of women. Humanness emerges as a concept that runs an integrating thread through a variety of research literatures.

  15. The Human Toolmaker

    OpenAIRE

    Kassuba, Tanja; Kastner, Sabine

    2014-01-01

    Do you enjoy building airplanes, cars, houses, or robots with Lego blocks? Humans are the only animal species that can create complicated constructions from simple Lego blocks – our Lego building ability is “human-specific,” since it is only found in human beings. What would our closest relatives, apes or monkeys, do with a box of Lego blocks? They would probably chew on them, and lose interest when they find out that they are not edible! Why are humans the only Lego builders in the animal ki...

  16. Photography after the Human

    OpenAIRE

    Zylinska, Joanna

    2016-01-01

    How can we visualise and subsequently reimagine the abstraction that is the extinction of human species while there is still time? The article addresses this question by considering the existence of images – and, in particular, light-induced mechanical images known as photographs – after the human. The “after the human” designation does not just refer to the material disappearance of the human in some kind of distant future, but also to the present imagining of the disappearance of the human ...

  17. Refractoriness in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Jespersen, Thomas; Christ, Torsten

    2016-01-01

    drugs. Cardiomyocyte excitability depends on availability of sodium channels, which involves both time- and voltage-dependent recovery from inactivation. This study therefore aims to characterise how sodium channel inactivation affects refractoriness in human atria. METHODS AND RESULTS: Steady......-state activation and inactivation parameters of sodium channels measured in vitro in isolated human atrial cardiomyocytes were used to parameterise a mathematical human atrial cell model. Action potential data were acquired from human atrial trabeculae of patients in either sinus rhythm or chronic atrial...... in pharmacological management of chronic atrial fibrillation....

  18. Humanities, Digital Humanities, Media studies, Internet studies

    DEFF Research Database (Denmark)

    Brügger, Niels

    the interplay between four areas which until now to a certain extent have been separated: Traditional Hu- manities, Digital Humanities, Media studies, and Internet studies. The vision is followed by an outline of how it can be unfolded in concrete activities, in the form of research projects, research...

  19. Developing Human Resources through Actualizing Human Potential

    Science.gov (United States)

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  20. Human Rights, History of

    NARCIS (Netherlands)

    de Baets, Antoon; Wright, James

    2015-01-01

    In this article, six basic debates about human rights are clarified from a historical perspective: the origin of human rights as moral rights connected to the natural law doctrine and opposed to positive rights; the wave of criticism of their abstract and absolute character by nineteenth-century

  1. Introduction to human factors

    Energy Technology Data Exchange (ETDEWEB)

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  2. Human Capital and Retirement

    NARCIS (Netherlands)

    P. Alders

    1999-01-01

    textabstractThis paper investigates the relation between human capital and retirement when the age of retirement is endogenous. This relation is examined in a life-cycle earnings model. An employee works full time until retirement. The worker accumulates human capital by training- on-the-job and by

  3. Cohabitation: Humans & Agriculture

    NARCIS (Netherlands)

    Woodington, W.

    2012-01-01

    This "designers' manual" is made during the TIDO-course AR0531 Smart & Bioclimatic Design. Cohabitation of humans and agriculture can be used to improve building climate, human health and the state of the world. It affects building design and requires new building components. This manual explains w

  4. Manage "Human Capital" Strategically

    Science.gov (United States)

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  5. Human Resource Accounting

    Science.gov (United States)

    Woodruff, Robert L., Jr.

    1973-01-01

    An interview is reported which discussed the implications for the hiring, recruiting, screening and development of employees in the light of human resource accounting, here defined as the identification, accumulation and dissemination of information about human resources in dollar terms. (SA)

  6. Hooking Kids with Humanities.

    Science.gov (United States)

    Anstead, Neil L.

    1993-01-01

    Humanitas is part of Collaboratives for Humanities and Arts Teaching (CHART), a nationwide network funded primarily by the Rockefeller Foundation. In 11 large school districts and numerous rural districts, high school teachers, academics, artists, and business and community leaders are cooperating to promote teaching of the arts and humanities.…

  7. The Human Technology

    DEFF Research Database (Denmark)

    Fausing, Bent

    with fundamental human values like intuition, vision and sensing; all the qualities the technology, the industrialisation and rationalisation, or in short modernity, has been criticized for having taken away from human existence. What technology has taken away now comes back through new technology as an aid...

  8. Manage "Human Capital" Strategically

    Science.gov (United States)

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  9. Translating the human microbiome

    NARCIS (Netherlands)

    Brown, J.; Vos, de W.M.; Distefano, P.S.; Doré, J.; Huttenhower, C.; Knight, R.; Lawley, T.D.; Raes, J.; Turnbaugh, P.

    2013-01-01

    Over the past decade, an explosion of descriptive analyses from initiatives, such as the Human Microbiome Project (HMP) and the MetaHIT project, have begun to delineate the human microbiome. Inhabitants of the intestinal tract, nasal passages, oral cavities, skin, gastrointestinal tract and urogenit

  10. Human Rights Guaranteed

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Report says China’s human rights plan successfully implemented According to a detailed assessment report published by China’s State Council Information Office (SCIO),all the measures outlined in the National Human Rights Action Plan of China (2009-10) had been successfully put into place by the end of 2010.

  11. Defects in Human Nature

    Institute of Scientific and Technical Information of China (English)

    黄靓

    2008-01-01

    By tracing the defects of society back to the defects of human nature, humanity's essence is proved to be inherent evil. Man's natural tendency to do evil remain harnessed through the controls and conventions imposed by civilization, however, when rules or civilization are weakened, man' s dark side is unleashed.

  12. Humanism within Globalization

    Science.gov (United States)

    Weber, Jennifer E.

    2014-01-01

    The complexity of adult learning connects it to almost all other facets of human endeavor. Consequently, the future of adult education depends, to a large extent on who participates and the quality of such participation. Quality participation, when teamed with environments committed to a concern for humanity, launches opportunities for varied…

  13. Report Details Human Resources

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China issues its first white paper on human resources The Chinese Government issued a white paper on its human resources on September 10, highlighting the country’s policies to cope with employment pressures and a lack of "high-level innovative talents.

  14. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    2008-01-01

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a Colo

  15. Humanism within Globalization

    Science.gov (United States)

    Weber, Jennifer E.

    2014-01-01

    The complexity of adult learning connects it to almost all other facets of human endeavor. Consequently, the future of adult education depends, to a large extent on who participates and the quality of such participation. Quality participation, when teamed with environments committed to a concern for humanity, launches opportunities for varied…

  16. Damping Effect of Humans

    DEFF Research Database (Denmark)

    Pedersen, Lars

    Passive humans (sitting or standing) might well be present on flooring-systems, footbridges or other structures that carry humans. An active croud of people might generate structural vibrations, and these might be problematic. The passive crowd of people, however, will interact with the structural...

  17. Human Mind Maps

    Science.gov (United States)

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  18. Translating the human microbiome

    NARCIS (Netherlands)

    Brown, J.; Vos, de W.M.; Distefano, P.S.; Doré, J.; Huttenhower, C.; Knight, R.; Lawley, T.D.; Raes, J.; Turnbaugh, P.

    2013-01-01

    Over the past decade, an explosion of descriptive analyses from initiatives, such as the Human Microbiome Project (HMP) and the MetaHIT project, have begun to delineate the human microbiome. Inhabitants of the intestinal tract, nasal passages, oral cavities, skin, gastrointestinal tract and urogenit

  19. Human Resource Construction

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Centering on strategic objective of reform and development,CIAE formulated its objectives in human resource construction for the 13th Five-year Plan period,and achieved new apparent progress in human resource construction in 2015.1 Implementation of"LONGMA Project"

  20. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  1. Human Rights Improving

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China issues a white paper on its human rights,highlighting freedom of speech on the Interne The Chinese Government released a white paper on its human rights in 2009 on September 26,highlighting the role of Internet freedom and the country’s efforts in safeguarding citizens’legitimate civil and political rights.

  2. Human Rights, History of

    NARCIS (Netherlands)

    de Baets, Antoon; Wright, James

    2015-01-01

    In this article, six basic debates about human rights are clarified from a historical perspective: the origin of human rights as moral rights connected to the natural law doctrine and opposed to positive rights; the wave of criticism of their abstract and absolute character by nineteenth-century lib

  3. Designing Human Technologies

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    and the design process, in ethical and society-related concerns, and in evaluating how designs fulfill needs and solve problems. Designing Human Technologies subscribes to a broad technology concept including information and communication, mobile, environmental/sustainable and energy technologies......, the Humanities, and Social Science. The initiative broadens the perspective of IS and recognize reflections on aesthetics, ethics, values, connections to politics, and strategies for enabling a better future as legitimate parts of the research agenda. Designing Human Technologies is a design-oriented Strategic...... a shared interdisciplinary research and educational collaboration. As a creative research initiative it focuses on change and innovative thinking. The innovativeness is a result of the strongly interdisciplinary perspective which is at the heart of Designing Human Technologies. Designing Human Technologies...

  4. Human Relations-skolen

    DEFF Research Database (Denmark)

    Scheuer, Steen

    2014-01-01

    Human Relations-skolen er en samlebetegnelse for to forskningsretninger, som tilsammen bidrog som nogle af de første til at indkredse og belyse de mellemmenneskelige relationers betydning for motivation og trivsel i arbejdslivet, og som skulle få stor ind"ydelse ikke bare på organisationsteorien......, som formulerede en række teorier og modeller om menneskets motivation, trivsel og behov i arbejdslivet. Selvom de ikke nødvendigvis relaterede sig til hinandens arbejde, er de forskellige bidragsydere i dag kendt som repræsentanter for den paradigmatiske betegnelse Human Relations. Undertiden skelnes...... der mellem Human Relations (Hawthorne-eksperimenter ne) og Neo-Human Relations (behovsteorierne), men i denne fremstilling bruges Human Relations som en samlebetegnelse for begge disse – noget forskellige – forskningstraditioner. De har i dag opnået stor udbredelse og er praktisk talt obligatorisk...

  5. Pomegranate for your cardiovascular health.

    Science.gov (United States)

    Aviram, Michael; Rosenblat, Mira

    2013-04-01

    Pomegranate is a source of some very potent antioxidants (tannins, anthocyanins) which are considered to be also potent anti-atherogenic agents. The combination of the above unique various types of pomegranate polyphenols provides a much wider spectrum of action against several types of free radicals. Indeed, pomegranate is superior in comparison to other antioxidants in protecting low-density lipoprotein (LDL, "the bad cholesterol") and high-density lipoprotein (HDL, "the good cholesterol") from oxidation, and as a result it attenuates atherosclerosis development and its consequent cardiovascular events. Pomegranate antioxidants are not free, but are attached to the pomegranate sugars, and hence were shown to be beneficial even in diabetic patients. Furthermore, pomegranate antioxidants are unique in their ability to increase the activity of the HDL-associated paraoxonase 1 (PON1), which breaks down harmful oxidized lipids in lipoproteins, in macrophages, and in atherosclerotic plaques. Finally, unique pomegranate antioxidants beneficially decrease blood pressure. All the above beneficial characteristics make the pomegranate a uniquely healthy fruit.

  6. Oxidative stress and DNA damage in horses naturally infected with Theileria equi.

    Science.gov (United States)

    Radakovic, M; Davitkov, D; Borozan, S; Stojanovic, S; Stevanovic, J; Krstic, V; Stanimirovic, Z

    2016-11-01

    The aim of this study was to determine the concentrations of oxidative stress parameters and DNA damage in horses infected by Theileria equi. Initial screening of 110 horses with duplex PCR enabled the selection of 30 infected horses with T. equi and 30 free of infection (control). Specimens from the 60 horses were further analysed by determining the following oxidative stress parameters: extent of haemolysis (EH), plasma free haemoglobin (PHb), catalase (CAT), Cu,Zn superoxide dismutase (SOD1), paraoxonase (PON1), nitrite (NO2(-)), total nitrate and nitrite (NOx), malondialdehyde (MDA) and free thiol groups (-SH). In addition, relative distribution of lactate dehydrogenase (LDH1-LDH5) activity and the DNA-damaging effects of T. equi infection were evaluated. Compared to control horses, horses infected with T. equi had significantly higher SOD1 activities (P horses had significantly increased LDH5 isoenzyme activities (P horses, which resulted in changes in osmotic fragility, damage to lipids, proteins and DNA, haemolysis and hepatocellular damage. Oxidative stress in horses naturally infected with T. equi could contribute to the pathogenesis of the infection.

  7. Oxidative stress in the pathophysiology of metabolic syndrome: which mechanisms are involved?

    Directory of Open Access Journals (Sweden)

    Thalia M. T. Avelar

    2015-08-01

    Full Text Available ABSTRACTMetabolic syndrome (MS is a combination of cardiometabolic risk factors, including obesity, hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension. Several studies report that oxidative condition caused by overproduction of reactive oxygen species (ROS plays an important role in the development of MS. Our body has natural antioxidant system to reduce oxidative stress, which consists of numerous endogenous and exogenous components and antioxidants enzymes that are able to inactivate ROS. The main antioxidant defense enzymes that contribute to reduce oxidative stress are superoxide dismutase (SOD, catalase (CAT and gluthatione peroxidase (GPx. The high-density lipoprotein cholesterol (HDL-c is also associated with oxidative stress because it presents antioxidant and anti-inflammatory properties. HDL-c antioxidant activity may be attributed at least in part, to serum paraoxonase 1 (PON1 activity. Furthermore, derivatives of reactive oxygen metabolites (d-ROMs also stand out as acting in cardiovascular disease and diabetes, by the imbalance in ROS production, and close relationship with inflammation. Recent reports have indicated the gamma-glutamyl transferase (GGT as a promising biomarker for diagnosis of MS, because it is related to oxidative stress, since it plays an important role in the metabolism of extracellular glutathione. Based on this, several studies have searched for better markers for oxidative stress involved in development of MS.

  8. Highly specific changes in antioxidant levels and lipid peroxidation in Parkinson's disease and its progression: Disease and staging biomarkers and new drug targets.

    Science.gov (United States)

    de Farias, Carine Coneglian; Maes, Michael; Bonifácio, Kamila Landucci; Bortolasci, Chiara Cristina; de Souza Nogueira, André; Brinholi, Francis Fregonesi; Matsumoto, Andressa Keiko; do Nascimento, Matheus Amarante; de Melo, Lúcio Baena; Nixdorf, Suzana Lucy; Lavado, Edson Lopes; Moreira, Estefânia Gastaldello; Barbosa, Décio Sabbatini

    2016-03-23

    There is evidence that immune-inflammatory, stress of reactive oxygen and nitrogen species (IO&NS) processes play a role in the neurodegenerative processes observed in Parkinson's disease (PD). The aim of the present study was to investigate peripheral IO&NS biomarkers in PD. We included 56 healthy individuals and 56 PD patients divided in two groups: early PD stage and late PD stage. Plasma lipid hydroperoxides (LOOH), malondialdehyde (MDA), nitric oxide metabolites (NOx), sulfhydryl (SH) groups, catalase (CAT) activity, superoxide dismutase (SOD) activity, paraoxonase (PON)1 activity, total radical trapping antioxidant parameter (TRAP) and C-reactive protein (CRP) were measured. PD is characterized by increased LOOH, MDA and SOD activity and lowered CAT activity. A combination of five O&NS biomarkers highly significantly predicts PD with a sensitivity of 94.5% and a specificity of 86.8% (i.e., MDA, SOD activity, TRAP, SH-groups and CAT activity). The single best biomarker of PD is MDA, while LOOH and SOD activity are significantly associated with late PD stage, but not early PD stage. Antiparkinson drugs did not affect O&NS biomarkers, but levodopa+carbidopa significantly increased CRP. It is suggested that MDA may serve as a disease biomarker, while LOOH and SOD activity are associated with late PD stage characteristic. New treatments for PD should not only target dopamine but also lipid peroxidation.

  9. Dietary flaxseed oil and fish oil modulates expression of antioxidant and inflammatory genes with alleviation of protein glycation status and inflammation in liver of streptozotocin-nicotinamide induced diabetic rats.

    Science.gov (United States)

    Jangale, Nivedita M; Devarshi, Prasad P; Dubal, Aarti A; Ghule, Arvindkumar E; Koppikar, Soumya J; Bodhankar, Subhash L; Chougale, Ashok D; Kulkarni, Mahesh J; Harsulkar, Abhay M

    2013-11-01

    Beneficial effects of dietary flaxseed oil or fish oil on streptozotocin-nicotinamide induced diabetic rats were investigated. Rats were divided into three diabetic and three non-diabetic groups and received control, flaxseed oil or fish oil diets (10%w/w). Both diets reduced blood glucose, TBARS and hepatic NO. The extent of glycation measured in terms of glycated albumin and hemoglobin was reduced significantly with both diets. Flaxseed oil diet up-regulated hepatic catalase (CAT) (activity and expression), superoxide dismutase (SOD) (activity and expression) and glutathione peroxidase (GPx) expression. Fish oil diet up-regulated hepatic CAT (activity and expression), paraoxonase-1 (PON-1) expression and down-regulated heme oxygenase-1 (HO-1) expression. Furthermore, both diets down-regulated the expression of hepatic inflammatory genes TNF-α, IL-6, MCP-1, INF-γ and NF-κB. These results were supported by histopathological observations which showed better tissue preservation in both the diets. Thus, both the diets proved to be beneficial in preventing tissue injury and alleviating diabetic insults in the livers of STZ-NIC diabetic rats.

  10. Supplementation with imuno-2865® in gilthead sea bream (Sparus aurata Linnaeus, 1758): Effects on hematological and antioxidant parameters.

    Science.gov (United States)

    Župan, Ivan; Tkalčić, Suzana; Šarić, Tomislav; Čož-Rakovac, Rozalindra; Strunjak-Perović, Ivančica; Topić-Popović, Natalija; Kardum, Matko; Kanski, Danijel; Ljubić, Blanka Beer; Matijatko, Vesna; Poljičak-Milas, Nina

    2015-11-01

    The aim of this study was to evaluate the effects of IMUNO-2865(®) on hematological and antioxidative parameters in sea bream. Total of 640 sea bream were fed with diets containing 0 (Group 1), 1 (Group 2), 10 (Group 3) and 25 (Group 4) g of IMUNO-2865(®) kg(-1) feed during 90 days. Samples were taken each month and three months after the supplementation. A significant heterophils increase was observed in group 4 compared to group 1 after two months, and an increase in monocytes number was observed in group 4 compared to the other groups after one month. Glutathione peroxidase (GSH-Px) and paraoxonase-1 (PON1) were significantly increased in groups 3 and 4 compared to the control group three months into the experiment. Superoxide dismutase (SOD) was increased in group 4 compared to the control group from day 60 until the end of the experiment, and in groups 2 and 3 compared to the control after three months. Based on the differences in the cellular immunity and oxidative stress parameters, with an overall absence of mortality, the results of this study suggest that the use of IMUNO-2865(®) in aquaculture is safe and possess a cumulative immunostimulatory effect on sea bream.

  11. The influence of maternal smoking habits before pregnancy and antioxidative supplementation during pregnancy on oxidative stress status in a non-complicated pregnancy.

    Science.gov (United States)

    Ardalić, Daniela; Stefanović, Aleksandra; Kotur-Stevuljević, Jelena; Vujović, Ana; Spasić, Slavica; Spasojević-Kaliomanvska, Vesna; Jelić-Ivanović, Zorana; Mandić-Marković, Vesna; Miković, Zeljko; Cerović, Nikola

    2014-01-01

    As a physiological condition closely linked with increased susceptibility to oxidative stress, pregnancy can be further compromised by cigarette smoking. Inadequate nutrition and reduced intake of antioxidants can also disrupt the prooxidant/antioxidant relationship and contribute to oxidative stress. Increased oxidative stress during pregnancy may be involved in several complications of pregnancy, such as preterm labor, fetal growth restriction, preeclampsia and miscarriage. The aim of this study was to investigate the influence of maternal smoking habits before pregnancy on the parameters of oxidative stress and the antioxidative defense system, lipid profile parameters and paraoxonase-1 (PON1) activity during the third trimester of uncomplicated pregnancies. Healthy pregnant women (n = 86) were divided into non-smoking and smoking groups, and into groups taking vitamin supplements and not taking them. Oxidative damage was measured through the levels of thiobarbituric acid-reacting substances (TBARS) and plasma antioxidant status was evaluated by measuring total antioxidant capacity (TAC). TBARS concetration was significantly higher (p pregnancy is associated with increased oxidative stress. Vitamin supplementation has no effect on the oxidative stress status of healthy pregnant women.

  12. Altered Activities of Antioxidant Enzymes in Patients with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Lucie Vávrová

    2013-02-01

    Full Text Available Objective: In the pathogenesis of the metabolic syndrome (MetS, an increase of oxidative stress could play an important role which is closely linked with insulin resistance, endothelial dysfunction, and chronic inflammation. The aim of our study was to assess several parameters of the antioxidant status in MetS. Methods: 40 subjects with MetS and 40 age- and sex-matched volunteers without MetS were examined for activities of superoxide dismutase (CuZnSOD, catalase (CAT, glutathione peroxidase 1 (GPX1, glutathione reductase (GR, paraoxonase1 (PON1, concentrations of reduced glutathione (GSH, and conjugated dienes in low-density lipoprotein (CD-LDL. Results: Subjects with MetS had higher activities of CuZnSOD (p Conclusions: Our results implicated an increased oxidative stress in MetS and a decreased antioxidative defense that correlated with some laboratory (triglycerides, high-density lipoprotein cholesterol (HDL-C and clinical (waist circumference, blood pressure components of MetS.

  13. Anti-inflammatory and antioxidant functions of high-density lipoprotein subclasses in patients with acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Ying TAN

    2013-02-01

    Full Text Available Objective  To assess the anti-inflammatory and antioxidant functions of high-density lipoprotein (HDL subclasses (HDL2 and HDL3 in patients with acute coronary syndrome (ACS, and to elucidate whether incapacitation of HDL subclasses occurred in ACS patients. Methods  Forty ACS patients hospitalized in Nanfang Hospital from Jan. 2011 to Jan. 2012 (ACS group, and 40 subjects simultaneously receiving health examination (control group were enrolled in present study. Plasma lipid and hypersensitive C reactive protein (hs-CRP levels, HDL subclasses inflammatory index (HII, paraoxonase-1 (PON1 activity and lipid hydroperoxide (LOOH levels in both groups were measured. Results  The low-density lipoprotein cholesterol (LDL-C and hs-CRP levels were higher in ACS group than in control group (P0.05. Conclusions  The incapacitation of HDL subclasses may occur in ACS patients, with an attenuated antioxidant ability and accentuated proinflammatory function. Mature HDL2 possesses better anti-inflammatory and antioxidant function than HDL3, thus playing a better cardioprotective effect.

  14. The Effects of Levetiracetam on Cerebrospinal Fluid and Plasma NPY and GAL, and on the Components of Stress Response System, hs-CRP, and S100B Protein in Serum of Patients with Refractory Epilepsy.

    Science.gov (United States)

    Chen, Wenzhen; Tan, Yan; Ge, Yuxing; Chen, Yujuan; Liu, Xueyuan

    2015-11-01

    Our objective is to explore the effects of levetiracetam on the levels of neuropeptides, serum activity and concentrations of oxidative stress and inflammatory response proteins, and levels of brain injury marker in patients with refractory epilepsy. Seventy-two patients with refractory epilepsy received levetiracetam treatment. Neuropeptides galanin (GAL) and neuropeptide Y (NPY) in plasma and cerebrospinal fluid (CSF) were detected using double-antibody sandwich immunoassay and radioimmunoassay, respectively. Enzyme-linked immunosorbent assay was used to detect serum activity of paraoxonase (PON1) and serum concentrations of oxidized low-density lipoprotein (ox-LDL) and S100B. Arylesterase (ARE) activity was measured by colorimetric assay, and immune scatter turbidimetry was used to detect a high-sensitivity C-reactive protein (hs-CRP). After treatment, NPY and GAL in plasma and CSF of the patients were significantly decreased as compared to concentrations before treatment (P hs-CRP and S100B protein were significantly lower after levetiracetam administrations than before treatment (P hs-CRP, and S100B. Levetiracetam therefore may be considered a drug of choice for treating refractory epilepsy.

  15. Surgery-induced changes in red blood cell and plasma lipid peroxidation, enzymatic and non-enzymatic antioxidants, and blood hematology of female rats: protective role of methylene blue and vitamin E.

    Science.gov (United States)

    Yildiz, Hamit; Durmus, Ali Said; Simsek, Halil

    2011-03-01

    The aim was to determine the effects on red blood cell (RBC) and plasma lipid peroxidation, antioxidants and blood hematology of intraperitoneally administered vitamin E (VE) and 1% methylene blue (MB) solutions for prevention of adhesions in rats. Thirty-seven female Sprague-Dawley rats were randomized into four groups. An adhesion model was constituted on the left uterine horn in three of the groups. They were then given intraperitoneally 0.9% saline (C group), 10 mg VE (VE group) and 1% MB (MB group) solutions, respectively. A sham group (Sh group), on which laparotomy was performed, received 2 ml of 0.9% saline solution. In the C group, the adhesion scores were significantly higher than in the VE (pblood lymphocyte count (pblood white blood cell (WBC) counts (pblood WBC counts (p<0.01), plasma paraoxonase (PON1) (p<0.001) and NO (p<0.01), and RBC glutathione peroxidase (GPx) activity (p<0.05) and MDA levels (p<0.01). Intraperitoneal administration of MB and VE is significantly effective in preventing intraabdominal adhesion formation in a rat model. Further investigations are necessary, however, to better understand the underlying biochemical mechanisms on lipid peroxidation and antioxidants of MB. Published by Elsevier Ireland Ltd.

  16. Oxidative stress, HDL functionality and effects of intravenous iron administration in women with iron deficiency anemia.

    Science.gov (United States)

    Meroño, Tomás; Dauteuille, Carolane; Tetzlaff, Walter; Martín, Maximiliano; Botta, Eliana; Lhomme, Marie; Saez, María Soledad; Sorroche, Patricia; Boero, Laura; Arbelbide, Jorge; Chapman, M John; Kontush, Anatol; Brites, Fernando

    2017-04-01

    Iron deficiency anemia (IDA) affects around 20-30% of adults worldwide. An association between IDA and cardiovascular disease (CVD) has been reported. Oxidative stress, inflammation and low concentration of high-density lipoproteins (HDL) were implicated on endothelial dysfunction and CVD in IDA. We studied the effects of iron deficiency and of an intravenous iron administration on oxidative stress and HDL characteristics in IDA women. Two studies in IDA women are presented: a case-control study, including 18 patients and 18 age-matched healthy women, and a follow-up study 72hr after the administration of intravenous iron (n = 16). Lipids, malondialdehyde, cholesteryl ester transfer protein (CETP), paraoxonase-1 (PON-1) and HDL chemical composition and functionality (cholesterol efflux and antioxidative activity) were measured. Cell cholesterol efflux from iron-deficient macrophages to a reference HDL was also evaluated. IDA patients showed higher triglycerides and CETP activity and lower HDL-C than controls (all p HDL particles from IDA patients showed higher triglyceride content (+30%,p HDL-mediated cholesterol efflux was similar between the patients and controls, iron deficiency provoked a significant reduction in macrophage cholesterol efflux (-25%,p HDL particles. It remains to be determined if such alterations suffice to impair endothelial function in IDA. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  17. Human to Human Transmission of Brucella Melitensis

    Directory of Open Access Journals (Sweden)

    Patrice Vigeant

    1995-01-01

    Full Text Available Human brucellosis is acquired mainly through contact with infected animal tissues, ingestion of unpasteurized dairy products or infected aerosols. Person to person transmission is still considered uncertain. The case of a woman diagnosed with proven brucellosis after her husband suffered a relapse of bacteremia with Brucella melitensis biotype 3, which was originally acquired abroad by eating goat cheese, is described. It was postulated that person to person spread of brucellosis is a likely mode of transmission in this case.

  18. Human to Human Transmission of Brucella Melitensis

    OpenAIRE

    Patrice Vigeant; Jack Mendelson; Miller, Mark A.

    1995-01-01

    Human brucellosis is acquired mainly through contact with infected animal tissues, ingestion of unpasteurized dairy products or infected aerosols. Person to person transmission is still considered uncertain. The case of a woman diagnosed with proven brucellosis after her husband suffered a relapse of bacteremia with Brucella melitensis biotype 3, which was originally acquired abroad by eating goat cheese, is described. It was postulated that person to person spread of brucellosis is a likely ...

  19. Archaea on human skin.

    Directory of Open Access Journals (Sweden)

    Alexander J Probst

    Full Text Available The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin microbiome. Most of the gene signatures analyzed belonged to the Thaumarchaeota, a group of Archaea we also found in hospitals and clean room facilities. The metabolic potential for ammonia oxidation of the skin-associated Archaea was supported by the successful detection of thaumarchaeal amoA genes in human skin samples. However, the activity and possible interaction with human epithelial cells of these associated Archaea remains an open question. Nevertheless, in this study we provide evidence that Archaea are part of the human skin microbiome and discuss their potential for ammonia turnover on human skin.

  20. Human Power Empirically Explored

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, A.J.

    2011-01-18

    Harvesting energy from the users' muscular power to convert this into electricity is a relatively unknown way to power consumer products. It nevertheless offers surprising opportunities for product designers; human-powered products function independently from regular power infrastructure, are convenient and can be environmentally and economically beneficial. This work provides insight into the knowledge required to design human-powered energy systems in consumer products from a scientific perspective. It shows the developments of human-powered products from the first introduction of the BayGen Freeplay radio in 1995 till current products and provides an overview and analysis of 211 human-powered products currently on the market. Although human power is generally perceived as beneficial for the environment, this thesis shows that achieving environmental benefit is only feasible when the environmental impact of additional materials in the energy conversion system is well balanced with the energy demands of the products functionality. User testing with existing products showed a preference for speeds in the range of 70 to 190 rpm for crank lengths from 32 to 95 mm. The muscular input power varied from 5 to 21 W. The analysis of twenty graduation projects from the Faculty of Industrial Design Engineering in the field of human-powered products, offers an interesting set of additional practice based design recommendations. The knowledge based approach of human power is very powerful to support the design of human-powered products. There is substantial potential for improvements in the domains energy conversion, ergonomics and environment. This makes that human power, when applied properly, is environmentally and economically competitive over a wider range of applications than thought previously.

  1. Human pancreas development.

    Science.gov (United States)

    Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

    2015-09-15

    A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes.

  2. Enhancing human capacities

    CERN Document Server

    Savulescu, Julian; Kahane, Guy

    2011-01-01

    Enhancing Human Capacities is the first to review the very latest scientific developments in human enhancement. It is unique in its examination of the ethical and policy implications of these technologies from a broad range of perspectives. Presents a rich range of perspectives on enhancement from world leading ethicists and scientists from Europe and North America The most comprehensive volume yet on the science and ethics of human enhancement Unique in providing a detailed overview of current and expected scientific advances in this area Discusses both general conceptual and ethical issues

  3. Aluminium in human sweat.

    Science.gov (United States)

    Minshall, Clare; Nadal, Jodie; Exley, Christopher

    2014-01-01

    It is of burgeoning importance that the human body burden of aluminium is understood and is measured. There are surprisingly few data to describe human excretion of systemic aluminium and almost no reliable data which relate to aluminium in sweat. We have measured the aluminium content of sweat in 20 healthy volunteers following mild exercise. The concentration of aluminium ranged from 329 to 5329μg/L. These data equate to a daily excretion of between 234 and 7192μg aluminium and they strongly suggest that perspiration is the major route of excretion of systemic aluminium in humans. Copyright © 2013 Elsevier GmbH. All rights reserved.

  4. Human exposure to aluminium.

    Science.gov (United States)

    Exley, Christopher

    2013-10-01

    Human activities have circumvented the efficient geochemical cycling of aluminium within the lithosphere and therewith opened a door, which was previously only ajar, onto the biotic cycle to instigate and promote the accumulation of aluminium in biota and especially humans. Neither these relatively recent activities nor the entry of aluminium into the living cycle are showing any signs of abating and it is thus now imperative that we understand as fully as possible how humans are exposed to aluminium and the future consequences of a burgeoning exposure and body burden. The aluminium age is upon us and there is now an urgent need to understand how to live safely and effectively with aluminium.

  5. Human dignity and bioethics

    Directory of Open Access Journals (Sweden)

    Marjanović Miloš

    2013-01-01

    Full Text Available By opening the field of bioethics followed a new wave of intense debate on the theological, philosophical and legal significance of the concept of human dignity . Exactly ten years ago (December 2003 American bioethicist Ruth Maclin has proposed to divest ourselves of the concept of human dignity because it is vague, useless and redundant and that, without any loss, we can replace it by the ethical principle of personal autonomy. Her article was followed by harsh reactions and opposite views. What is this term in so broad, almost inflationary and opposite use is not a reason to deprive him, but, on the contrary, it shows how important it is and that it should be determined at least outline. As universal values and general concept, the human dignity has no pre-defined and narrow, precise meaning. It is more an evaluation horizon, the guiding principle and regulatory ideas that must constantly define and codify by many guaranted human rights and fundamental freedoms. As generic notion of each reasonable law, it is their foundation and a common denominator, legitimising basis of natural but also of positive law. As intrinsic and static value which means the humaneness, the humanity it is absolute, inherent to every human being without distinction and conditioning, as a unique and unrepeatable creation. In this meaning, the dignity is the obligation and limitation of the state, society and each of us. As an ethical and dynamic category, it is not given to us, but it is assign to us, and it is not in us, but always before us, as a guide of our actions in accordance with virtues, to treat ourselves, each other and the nature in a human way. The century in which we live is named the century of molecular biology and genetic engineering because of the enormous potential but also risks to human dignity. Because of that human dignity has become a central principle in all international documents relating to the human genome, genetics and bioethics, adopted

  6. Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, W. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Fortson, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Joyce, G. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Kimble, H. J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Max, C. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Prince, T. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, P. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Woodin, W. H. [The MITRE Corporation, McLean, VA (US). JASON Program Office

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  7. Human Capital Tracking Tool -

    Data.gov (United States)

    Department of Transportation — AVS is now required to collect, track, and report on data from the following Flight, Business and Workforce Plan. The Human Resource Management’s Performance Target...

  8. Human Research Program

    Data.gov (United States)

    National Aeronautics and Space Administration — Strategically, the HRP conducts research and technology development that: 1) enables the development or modification of Agency-level human health and performance...

  9. Human Papillomavirus (HPV)

    Science.gov (United States)

    ... Español Text Size Email Print Share Human Papillomavirus (HPV) Page Content Article Body According to the Centers ... and how to prevent it. How to Prevent HPV: There are 3 types of HPV vaccine: Cervarix , ...

  10. Human Reliability Program Overview

    Energy Technology Data Exchange (ETDEWEB)

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  11. Human Emotion Recognition System

    Directory of Open Access Journals (Sweden)

    Dilbag Singh

    2012-08-01

    Full Text Available This paper discusses the application of feature extraction of facial expressions with combination of neural network for the recognition of different facial emotions (happy, sad, angry, fear, surprised, neutral etc... Humans are capable of producing thousands of facial actions during communication that vary in complexity, intensity, and meaning. This paper analyses the limitations with existing system Emotion recognition using brain activity. In this paper by using an existing simulator I have achieved 97 percent accurate results and it is easy and simplest way than Emotion recognition using brain activity system. Purposed system depends upon human face as we know face also reflects the human brain activities or emotions. In this paper neural network has been used for better results. In the end of paper comparisons of existing Human Emotion Recognition System has been made with new one.

  12. Humanism vs. Behaviorism

    Science.gov (United States)

    Hunter, Madeline

    1977-01-01

    Author argues that humanism and behaviorism are not necessarily exclusive of one another, and that principles of behaviorism, when thoughtfully applied, can lead to the achievement of humanistic goals. (RW)

  13. Bridging Humanism and Behaviorism.

    Science.gov (United States)

    Chu, Lily

    1980-01-01

    Humanistic behaviorism may provide the necessary bridge between behaviorism and humanism. Perhaps the most humanistic approach to teaching is to learn how certain changes will help students and how these changes can be accomplished. (Author/MLF)

  14. BIOETHICS AND HUMAN CLONING

    Directory of Open Access Journals (Sweden)

    Željko Kaluđerović

    2011-12-01

    Full Text Available In this paper the authors analyze the process of negotiating and beginning of the United Nations Declaration on Human Cloning as well as the paragraphs of the very Declaration. The negotiation was originally conceived as a clear bioethical debate that should have led to a general agreement to ban human cloning. However, more often it had been discussed about human rights, cultural, civil and religious differences between people and about priorities in case of eventual conflicts between different value systems. In the end, a non-binding Declaration on Human Cloning had been adopted, full of numerous compromises and ambiguous formulations, that relativized the original intention of proposer states. According to authors, it would have been better if bioethical discussion and eventual regulations on cloning mentioned in the following text had been left over to certain professional bodies, and only after the public had been fully informed about it should relevant supranational organizations have taken that into consideration.

  15. Human Resource Planning

    Science.gov (United States)

    Hoffman, W. H.; Wyatt, L. L.

    1977-01-01

    By using the total resource approach, we have focused attention on the need to integrate human resource planning with other business plans and highlighted the importance of a productivity strategy. (Author)

  16. Viruses and human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gallo, R.C.; Haseltine, W.; Klein, G.; Zur Hausen, H.

    1987-01-01

    This book contains papers on the following topics: Immunology and Epidemiology, Biology and Pathogenesis, Models of Pathogenesis and Treatment, Simian and Bovine Retroviruses, Human Papilloma Viruses, EBV and Herpesvirus, and Hepatitis B Virus.

  17. CHINESE OF HUMANITY

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Humanism Education in Language Class,Innovative model university English teaching,Analysis on Information Literacy of College English Teachers Based On Net Environment,Cultural Differences between E-C Idioms and Teaching of English Idioms

  18. Human Factors Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  19. Will Technology Humanize Us?

    Science.gov (United States)

    Snider, Robert C.

    1972-01-01

    The author considers the question of whether technology will cause humanization or dehumanization in the schools. He concludes that we can not stop tecchnology; we can only give it direction and purpose. (Author/MS)

  20. Report Details Human Resources

    Institute of Scientific and Technical Information of China (English)

    YIN PUMIN

    2010-01-01

    @@ The Chinese Government issued a white paper on its human resources on September I0, highlighting the coun-try's policies to cope with employ-ment pressures and a lack of "high-level innovative talents."

  1. Statement on Human Cloning

    Science.gov (United States)

    ... ban on efforts to implant a human cloned embryo for the purpose of reproduction. The scientific evidence ... stem cell research, including the use of nuclear transplantation techniques (also known as research or therapeutic cloning), ...

  2. Science and Humanism

    Science.gov (United States)

    Auger, Pierre

    1971-01-01

    Science and humanism are separated so completely as to bring about the creation of two cultures quite distinct from each other within contemporary civilization. Pragmatic, rational attitudes are needed on both sides to bring them together. (DF)

  3. Human Assisted Assembly Processes

    Energy Technology Data Exchange (ETDEWEB)

    CALTON,TERRI L.; PETERS,RALPH R.

    2000-01-01

    Automatic assembly sequencing and visualization tools are valuable in determining the best assembly sequences, but without Human Factors and Figure Models (HFFMs) it is difficult to evaluate or visualize human interaction. In industry, accelerating technological advances and shorter market windows have forced companies to turn to an agile manufacturing paradigm. This trend has promoted computerized automation of product design and manufacturing processes, such as automated assembly planning. However, all automated assembly planning software tools assume that the individual components fly into their assembled configuration and generate what appear to be a perfectly valid operations, but in reality the operations cannot physically be carried out by a human. Similarly, human figure modeling algorithms may indicate that assembly operations are not feasible and consequently force design modifications; however, if they had the capability to quickly generate alternative assembly sequences, they might have identified a feasible solution. To solve this problem HFFMs must be integrated with automated assembly planning to allow engineers to verify that assembly operations are possible and to see ways to make the designs even better. Factories will very likely put humans and robots together in cooperative environments to meet the demands for customized products, for purposes including robotic and automated assembly. For robots to work harmoniously within an integrated environment with humans the robots must have cooperative operational skills. For example, in a human only environment, humans may tolerate collisions with one another if they did not cause much pain. This level of tolerance may or may not apply to robot-human environments. Humans expect that robots will be able to operate and navigate in their environments without collisions or interference. The ability to accomplish this is linked to the sensing capabilities available. Current work in the field of cooperative

  4. [Demography and human ecology].

    Science.gov (United States)

    Nazareth, J M

    1993-01-01

    At the end of the 19th century the German biologist Ernest Haekel was the first scientist to use the term ecology, which was defined as the study of relationships of organisms or groups of organisms with the environment and indicated the interdependence of the living world, including plants, animals, and humans. This concept also indicates a continuous process of adaptation of organisms to their external environment. The basic concepts of scientific ecology, which developed at the end of the 19th century, can be attributed to Darwin: the relationships between living beings and the notion of the process of adaptation to their environment. The term human ecology appeared in the early 1920s. Human ecology embodies fundamental ideas: biotype, habitat, community, biocenosis, ecosystem, biomass, interchange and equilibrium, and circulation of energy. The accumulated knowledge about human ecology is broken down using the criteria of topography (ecology of humid forests, deserts, lakes, etc.); followed by the appearance of species; and the variants of classical division: auto ecology (influence of external factors on living beings) and sinecology (the study of groups of associated organisms, i.e., natural, animal, and vegetation communities). The species are considered on the basis of equality or sinecology (all of them have the same interests), while in human ecology a species is determined by its relation to a reference group--autoecology or anthropocentric ecology. In 1911, J. Thompson bridged the gap between biological knowledge and social sciences; in 1921, H. Barrows identified human ecology as a component of geography; in 1925, L. Bernard presented the classification of ecosystems; and in 1936, Ezra Park published his work, Human Ecology, followed in 1945 by the emergence of the Chicago school. Demography and human ecology are intimately connected because population is the result of natural and migratory movements, therefore the two sciences require a methodology

  5. Human Resources Accounting

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The 21 st century will be the epoch of knowled ge economy. Knowledge economy is to develop economy on the basis of knowledge will surely become the major resources of economy development. Therefore, human resources accounting which provides such information as the ebb and follow of hu man resources investment, the size of the human resources employment, will bec ome the main stream of accounting the time of knowledge economy. To face China 's reality, to develop economy, and to flourish enterprise...

  6. Human motricity and health

    Directory of Open Access Journals (Sweden)

    Manuel Sérgio Vieira e Cunha

    2008-06-01

    Full Text Available If human motricity science intends to study motor conduct (or actions in which the human being pursues transcendence (or surmounting, it inevitably relates to the large realm of health. What are the aspects it evinces? Transdisciplinarity, solidarity among the various knowledge types (including poetical, complexity, (where the physical is integrated but surmounted and the firm belief that to be healthy is to have in ourselves, alive and working, the capacity for surmounting anything.

  7. Human Happiness Is Sensuous

    Institute of Scientific and Technical Information of China (English)

    吕静

    2003-01-01

    All human happiness is biological happiness. That is strictly scientific. At the risk of being misunderstood. I must make it clearer: all human happiness is sensuous happiness. The spiritualists will misunderstand me. I am sure; the spiritualists and materialists must forever misunderstand each other, because they don’t talk the same language, or mean by the same word different things. Are we, too, in this problem

  8. Evolution and human sexuality.

    Science.gov (United States)

    Gray, Peter B

    2013-12-01

    The aim of this review is to put core features of human sexuality in an evolutionary light. Toward that end, I address five topics concerning the evolution of human sexuality. First, I address theoretical foundations, including recent critiques and developments. While much traces back to Darwin and his view of sexual selection, more recent work helps refine the theoretical bases to sex differences and life history allocations to mating effort. Second, I consider central models attempting to specify the phylogenetic details regarding how hominin sexuality might have changed, with most of those models honing in on transitions from a possible chimpanzee-like ancestor to the slightly polygynous and long-term bonded sociosexual partnerships observed among most recently studied hunter-gatherers. Third, I address recent genetic and physiological data contributing to a refined understanding of human sexuality. As examples, the availability of rapidly increasing genomic information aids comparative approaches to discern signals of selection in sexuality-related phenotypes, and neuroendocrine studies of human responses to sexual stimuli provide insight into homologous and derived mechanisms. Fourth, I consider some of the most recent, large, and rigorous studies of human sexuality. These provide insights into sexual behavior across other national samples and on the Internet. Fifth, I discuss the relevance of a life course perspective to understanding the evolution of human sexuality. Most research on the evolution of human sexuality focuses on young adults. Yet humans are sexual beings from gestation to death, albeit in different ways across the life course, and in ways that can be theoretically couched within life history theory.

  9. Meeting human needs

    Science.gov (United States)

    Nicogossian, Arnauld E.

    1992-01-01

    The degree of autonomy of future long duration manned missions will emphasize interactions between human operators and automated systems aimed at the most effective allocations of tasks between humans and machines. Knowledge of crewmembers' physical status, encompassing both capabilities and limitations, will also be critical during EVA and planetary roving missions; psychological evaluation and support, with a view to both individual health and group cohesion and productivity, may become a critical consideration. Attention is here given to crewmembers' medical and psychological vulnerabilities.

  10. Human bites - self-care

    Science.gov (United States)

    Bites - human - self-care ... Human bites can occur in 2 ways: If someone bites you If your hand comes into contact ... bite to express anger or other negative feelings. Human bites may be more dangerous than animal bites. ...

  11. Testing for Human Immunodeficiency Virus

    Science.gov (United States)

    ... education Fact Sheet PFS005: Testing for Human Immunodeficiency Virus AUGUST 2015 • Reasons for Getting Tested • Who Should ... For More Information • Glossary Testing for Human Immunodeficiency Virus Human immunodeficiency virus (HIV) is the virus that ...

  12. A WORLD BEYOND HUMAN

    Directory of Open Access Journals (Sweden)

    David Abram

    2013-12-01

    Full Text Available From an initial project to investigate the relationship between magic and traditional medicine as practiced by shamans in Southern rural Asia, the focus of attention gradually shifted to an awareness of the negotiation traditional medicine people or shamans exert between the human community and the larger community of beings. This attentiveness to a more-than-human world does not occur at a supernatural domain above nature or inside her personal self but is the result of the shaman’s special ability to project her consciousness horizontally to other forms of sensibility with which human existence is interwoven. The ecological function of the shaman is to maintain a constant balance between what is taken and what is given from the human community to the larger community. The spirits of indigenous cultures are not defined in opposition to materiality but are essentially those modes of intelligence or awareness that do not possess a human form. By exploring different landscapes, and the sensibility living in them, a new sensitivity is awoken that allows for communication with those intelligences. However, the drowning of these other voices in Western culture, which reduces otherness to an object, creates an uneasiness that is hardly perceived except as an inability to interact with anything more-than-human and its dire consequences in the form of “civilization’s” destructive behavior.

  13. Genomics of human longevity.

    Science.gov (United States)

    Slagboom, P E; Beekman, M; Passtoors, W M; Deelen, J; Vaarhorst, A A M; Boer, J M; van den Akker, E B; van Heemst, D; de Craen, A J M; Maier, A B; Rozing, M; Mooijaart, S P; Heijmans, B T; Westendorp, R G J

    2011-01-12

    In animal models, single-gene mutations in genes involved in insulin/IGF and target of rapamycin signalling pathways extend lifespan to a considerable extent. The genetic, genomic and epigenetic influences on human longevity are expected to be much more complex. Strikingly however, beneficial metabolic and cellular features of long-lived families resemble those in animals for whom the lifespan is extended by applying genetic manipulation and, especially, dietary restriction. Candidate gene studies in humans support the notion that human orthologues from longevity genes identified in lower species do contribute to longevity but that the influence of the genetic variants involved is small. Here we discuss how an integration of novel study designs, labour-intensive biobanking, deep phenotyping and genomic research may provide insights into the mechanisms that drive human longevity and healthy ageing, beyond the associations usually provided by molecular and genetic epidemiology. Although prospective studies of humans from the cradle to the grave have never been performed, it is feasible to extract life histories from different cohorts jointly covering the molecular changes that occur with age from early development all the way up to the age at death. By the integration of research in different study cohorts, and with research in animal models, biological research into human longevity is thus making considerable progress.

  14. Human Milk Fortification.

    Science.gov (United States)

    Simmer, Karen

    2015-01-01

    Human milk is the feed of choice for preterm infants. However, human milk does not provide enough nutrition, especially protein, for preterm infants to achieve target growth rates similar to those in utero (15-20 g/kg per day). Fortifiers for human milk, manufactured from bovine milk, are commercially available and routinely used for patients born milk fortifier that is manufactured from donor human milk is available in some developed countries and may confer some clinical benefits, including a reduction in necrotizing enterocolitis. Fortification can be added in a standardized protocol as per manufacturers' instructions. Human milk composition can be analyzed and fortification individualized to take into account the large variation from mother to mother. Alternatively, fortification can be increased in a stepwise manner based on assumed composition while monitoring blood urea levels for safety. The current aim is to prevent preterm infants dropping percentiles and falling below the 10th percentile at 36 weeks' corrected gestational age or discharge home. More data are required on how best to fortify human milk for preterm infants to achieve optimal growth, development and health outcomes in the long term. There is an urgent need for well-designed and informed randomized clinical trials in this vulnerable preterm population.

  15. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  16. Philosophical foundations of human rights

    CERN Document Server

    Liao, Matthew S

    2015-01-01

    What makes something a human right? What is the relationship between the moral foundations of human rights and human rights law? What are the difficulties of appealing to human rights? This book offers the first comprehensive survey of current thinking on the philosophical foundations of human rights. Divided into four parts, this book focusses firstly on the moral grounds of human rights, for example in our dignity, agency, interests or needs. 'Secondly, it looks at the implications that different moral perspectives on human rights bear for human rights law and politics. Thirdly, it discusses specific and topical human rights including freedom of expression and religion, security, health and more controversial rights such as a human right to subsistence. The final part discusses nuanced critical and reformative views on human rights from feminist, Kantian and relativist perspectives among others. The essays represent new and canonical research by leading scholars in the field. Each part is comprised of a set...

  17. Why Geo-Humanities

    Science.gov (United States)

    Graells, Robert Casals i.; Sibilla, Anna; Bohle, Martin

    2016-04-01

    Anthropogenic global change is a composite process. It consists of societal processes (in the 'noosphere') and natural processes (in the 'bio-geosphere'). The 'noosphere' is the ensemble of social, cultural or political insights ('shared subjective mental concepts') of people. Understanding the composite of societal and natural processes ('human geo-biosphere intersections'), which shapes the features of anthropogenic global change, would benefit from a description that draws equally on natural sciences, social sciences and humanities. To that end it is suggested to develop a concept of 'geo-humanities': This essay presents some aspects of its scope, discussing "knowledge that is to manage", "intentions that are to shape", "choices that are to justify" and "complexity that is to handle". Managing knowledge: That people understand anthropogenic global change requires their insights into how 'human geosphere intersections' function. Insights are formed ('processed') in the noosphere by means of interactions between people. Understanding how 'human geosphere intersections' functions combines scientific, engineering and economic studies with studies of the dynamics of the noosphere. Shaping intentions: During the last century anthropogenic global change developed as the collateral outcome of humankind's accumulated actions. It is caused by the number of people, the patterns of their consumption of resources, and the alterations of their environments. Nowadays, anthropogenic global chance is either an intentional negligence or a conscious act. Justifying choices: Humanity has alternatives how to alter Earth at planetary scale consciously. For example, there is a choice to alter the geo-biosphere or to adjust the noosphere. Whatever the choice, it will depend on people's world-views, cultures and preferences. Thus beyond issues whether science and technology are 'sound' overarching societal issues are to tackle, such as: (i) how to appropriate and distribute natural

  18. [Human ehrlichiosis. Review].

    Science.gov (United States)

    Arraga-Alvarado, C

    1994-12-01

    Human ehrlichiosis is a newly recognized tick-borne disease. Since 1935 Ehrlichia canis has been known as a cause of illness in dogs and other canine species, and for a few years it was related with human disease. In 1990, Ehrlichia chaffeensis was isolated from a man suspected of having ehrlichiosis. Partial sequencing of the rRNAS from the human isolate and E. canis, indicated that they are 98.7% related. More recently (May 1994) an "human granulocytic ehrlichiosis" have been reported in USA. PCR amplification and sequence of 16S rDNA, showed that the human isolate was virtually identical to those reported for E. phagocytophila y E. equi, organisms that cause ehrlichiosis in rumiant and in horses. Most patients shows fever, headache, malaise, nausea or vomiting, anorexia and in a minority of cases rash is present. Some of them have complications such as pulmonary infiltrates, gastrointestinal problems, renal dysfunction or failure, hepatoesplenomegaly, neurologic abnormalities, DIC and some times death. Leucopenia, thrombocytopenia and elevated liver enzyme values have been common findings. Tetracycline and cloramphenicol have been using in adults and children as especific theraphy.

  19. The human serum metabolome.

    Directory of Open Access Journals (Sweden)

    Nikolaos Psychogios

    Full Text Available Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca.

  20. Humanity and Sustainability

    Directory of Open Access Journals (Sweden)

    Shu-Kun Lin

    2011-09-01

    Full Text Available So far our open access publishing company MDPI (Multidisciplinary Digital Publishing Institute has published mainly science, medicine and technology journals. To become a multidisciplinary publisher, we launched the journal Sustainability [1]. More recently, we started to run several social science journals, including Societies [2], Religions [3], Administrative Sciences [4] and Behavioral Sciences [5]. Today we published the first paper [6] of the inaugural issue of Humanities (ISSN 2076-0787. This will be an international open access journal, publishing scholarly papers of high quality across all humanities disciplines. As a publisher, I would like to publish journals surrounding the topics of sustainability and I believe the humanities as a discipline of academic studies are very important. As a scientist, I believed science and technology will only benefit human beings. I was raised in a small village, living a very primitive life in a peasant family: no electricity, no machines, of course no TV and no refrigerator. Now, the life of my children is completely different. Even my own life has completely changed. I have witnessed very rapid changes: more and more machines are used to consume mineral resources and energy and to pollute the environment, in order to produce more and more powerful machines (we are also launching a journal titled Machines, in which the relationship between Man and machine should be an interesting topic.. Machines are more and more like human individuals consuming resources themselves (we are launching a journal titled Resources. [...