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Sample records for human paraoxonase pon1

  1. Relationship between human paraoxonase-1 activity and PON1 polymorphisms in Mexican workers exposed to organophosphate pesticides.

    Science.gov (United States)

    López-Flores, I; Lacasaña, M; Blanco-Muñoz, J; Aguilar-Garduño, C; Sanchez-Villegas, P; Pérez-Méndez, O A; Gamboa-Avila, R

    2009-07-24

    Paraoxonase-1 (PON1) is a serum enzyme which catalyzes the hydrolysis of organophosphate pesticides. In this study we conducted a cross-sectional study and reported on the distribution of three common genetic polymorphisms of the PON1 gene in a population of floriculture workers from Mexico as well as the association between those polymorphisms and other predictors with serum PON1 activity on paraoxon, diazoxon and phenylacetate. The genotype frequencies at position PON1(55) were 89% (LL), 10% (LM) and 0.6% (MM), at position PON1(192) they were 16% (QQ), 47% (QR) and 37% (RR), and 26% (TT), 42% (TC) and 32% (CC) at position PON1(-108). Thus, the frequencies of alleles L, Q and T were 0.94, 0.40 and 0.47, respectively. The PON1(55) polymorphism had no significant effect on serum PON1 activity on any substrate. We found a significant association between the PON1(192) polymorphism and PON1 activity towards paraoxon and diazoxon, which increased in genotypes as follows: 192RR>192QR>192QQ for paraoxonase activity and, inversely, 192QQ>192QR>192RR for diazoxonase activity. The PON1(-108) polymorphism also had a significant effect on PON1 activity level towards paraoxon in the following order among the genotype groups: -108CC>-108TC>-108TT. Serum PON1 activity towards diazoxon was not associated with the PON1(-108) polymorphism but it was influenced by the intensity exposure to pesticides at the floriculture industry and the years of the occupational exposure to pesticides. No polymorphism significantly influenced serum PON1 activity on phenylacetate.

  2. Paraoxonase 1 (PON1) status and substrate hydrolysis

    International Nuclear Information System (INIS)

    Richter, Rebecca J.; Jarvik, Gail P.; Furlong, Clement E.

    2009-01-01

    Paraoxonase 1 (PON1) hydrolyzes a number of organophosphorus (OP) compounds including insecticides and nerve agents. The in vivo efficacy of PON1 to protect against a specific OP exposure depends on the catalytic efficiency of hydrolysis. The Q192R polymorphism affects the catalytic efficiency of hydrolysis of some substrates and not others. While PON1 R192 hydrolyzes paraoxon approximately 9-times as efficiently as PON1 Q192 , the efficiency is insufficient to provide in vivo protection against paraoxon/parathion exposure. The two PON1 192 alloforms have nearly equivalent but higher catalytic efficiencies for hydrolyzing diazoxon (DZO) and provide equivalent in vivo protection against DZO exposures. On the other hand, PON1 R192 is significantly more efficient in hydrolyzing chlorpyrifos oxon (CPO) than PON1 Q192 and provides better protection against CPO exposure. Thus, for some exposures it is only the level of plasma PON1 that is important, whereas for others it is both plasma level and the PON1 192 alloform(s) present in plasma that are important. In no case is the plasma level of PON1 unimportant, provided that the catalytic efficiency is sufficient to protect against the exposure. Two-substrate enzyme assay/analysis protocols that reveal both PON1 plasma levels and PON1 192 phenotype (QQ; QR; RR) are designed to optimize the separation of PON1 192 phenotypes; however, they have not been optimized for evaluating in vivo rates of OP detoxication. This study describes the adaptation of a non-OP, two-substrate determination of PON1 status to the conversion of the PON1 status data to physiologically relevant rates of DZO and CPO detoxication. Conversion factors were generated for rates of hydrolysis of different substrates

  3. [Preparation and preliminary application of rabbit anti-human PON2 antibodies(paraoxonase-2)].

    Science.gov (United States)

    Chen, Miao; Yang, Jin-Ju; Li, Shu-Zhen; Liu, Xiao-Lan; Liu, Ying; Zhang, Lin-Jie; Gao, Jian-En; Sun, Qi-Hong

    2008-07-01

    To preparation and characterize the rabbit polyclonal antibodies against human PON2 (paraoxonase-2). A fragment of human PON2 gene which was of low homology with rabbits but of higher hydrophilicity and immunogenicity was selected for recombinant expression in prokaryotic expression system. The rabbits were immunized with the purified GST fusion protein 3 times. The specificity and sensitivity of the anti-human PON2 polyclonal antibodies were detected by Western blot and indirect immunofluorescence. The GST-PON2 fusion protein was highly expressed in Ecoli with a molecular weight of 46 kDa. Western blot analysis proved the rabbit polyclonal antibodies could specifically recognize 39 kDa native PON2 protein expressed in several cells and tissues, such as HeLa cells, U937 cells, and human liver tissue. Indirect immunofluorescence analysis confirmed that PON2 protein was located in the cytoplasm of SY5Y cells. The rabbit polyclonal antibodies against human PON2 can specifically recognize natural protein expressed in human cells and tissues, Which can be used for further study and clinical detection of human PON2.

  4. 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.

  5. Effect of moxifloxacin on oxidative stress, paraoxonase-1 (PON1 ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of moxifloxacin on paraoxonase-1 (PON1) activity, and serum oxidative stress in patients with multiple drug-resistant tuberculosis (MDR-TB). Methods: A total ofof 130 MDR-TB patients who were treated with moxifloxacin from October 2014 to October 2010 in Eastern Medical District of Linyi ...

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

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    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.

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

    International Nuclear Information System (INIS)

    Androutsopoulos, Vasilis P.; Kanavouras, Konstantinos; Tsatsakis, Aristidis M.

    2011-01-01

    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. 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.

  9. 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.

  10. 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.

  11. 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....

  12. Paraoxonase (PON)-1 activity in overweight and obese children and adolescents: association with obesity-related inflammation and oxidative stress

    NARCIS (Netherlands)

    Krzystek-Korpacka, Małgorzata; Patryn, Eliza; Hotowy, Katarzyna; Czapińska, Elżbieta; Majda, Jacek; Kustrzeba-Wójcicka, Irena; Noczyńska, Anna; Gamian, Andrzej

    2013-01-01

    Paraoxonase-1 (PON1) is a HDL-attached extracellular esterase which is believed to contribute to the anti-atherogenic and anti-inflammatory properties of HDL. A decrease in PON1 is a risk factor for cardiovascular disease and has recently been found to be associated with juvenile obesity. The issue

  13. Paraoxonase 1 192 and 55 polymorphisms in osteosarcoma.

    Science.gov (United States)

    Ergen, Arzu; Kılıcoglu, Onder; Ozger, Harzem; Agachan, Bedia; Isbir, Turgay

    2011-08-01

    Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stres. Previous studies suggested that involved an amino acid substitution at position 192 gives rise to two alloenzymes with a low activity (Q allele) and a high activity (R allele) towards paraoxon. There also exists a second polymorphism of the human PON1 gene affecting amino acid 55, giving rise to a leucine (L-allele) substitution for methionine (M-allele). PON1 gene polymorphisms were studied in 50 patients with osteosarcoma and 50 healthy controls. Paraoxonase genotypes were determined by PCR-RFLP. We found a reduction in the frequency of PON1 192 R allele in patients (P=0.015). Besides, PON1 192 wild type QQ genotype (P=0.015) and PON1 55 wild type L allele (P=0.001) were higher in patients compared to healthy controls. PON1 192 QQ genotype was associated with osteosarcoma in multivariate logistic regression analysis. Our findings have suggested that PON1 192 wild type genotypes may be associated with a risk of developing osteosarcoma.

  14. Toxicity of chlorpyrifos and chlorpyrifos oxon in a transgenic mouse model of the human paraoxonase (PON1) Q192R polymorphism

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

    2005-08-01

    The Q192R polymorphism of paraoxonase (PON1) has been shown to affect hydrolysis of organophosphorus compounds. The Q192 and R192 alloforms exhibit equivalent catalytic efficiencies of hydrolysis for diazoxon, the oxon form of the pesticide (DZ). However, the R192 alloform has a higher catalytic efficiency of hydrolysis than does the Q192 alloform for chlorpyrifos oxon (CPO), the oxon form of the pesticide chlorpyrifos (CPS). The current study examined the relevance of these observations for in-vivo exposures to chlorpyrifos and chlorpyrifos oxon. Methods Using a transgenic mouse model we examined the relevance of the Q192R polymorphism for exposure to CPS and CPO in vivo. Transgenic mice were generated that expressed either human PON1Q192 or PON1R192 at equivalent levels, in the absence of endogenous mouse PON1. Dose-response and time course experiments were performed on adult mice exposed dermally to CPS or CPO. Morbidity and acetylcholinesterase (AChE) activity in the brain and diaphragm were determined in the first 24 h following exposure. Results Mice expressing PON1Q192 were significantly more sensitive to CPO, and to a lesser extent CPS, than were mice expressing PON1R192. The time course of inhibition following exposure to 1.2 mg/kg CPO revealed maximum inhibition of brain AChE at 6?12 h, with PON1R192, PON1Q192, and PON1? /? mice exhibiting 40, 70 and 85% inhibition, respectively, relative to control mice. The effect of PON1 removal on the dose?response curve for CPS exposure was remarkably consistent with a PBPK/PD model of CPS exposure. Conclusion These results indicate that individuals expressing only the PON1Q192 allele would be more sensitive to the adverse effects of CPO or CPS exposure, especially if they are expressing a low level of plasma PON1Q192.

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

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    Aneta Otocka-Kmiecik

    2009-12-01

    Full Text Available Paraoxonase 1 ([i]PON1[/i] is a member of a three-gene family ([i]PON1, PON2[/i], and [i]PON3[/i]. 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 [i]PON1[/i] blood concentration and activity are modified by environmental and lifestyle factors as well as [i]PON1[/i] polymorphism.

  16. Repeated Gestational Exposure of Mice to Chlorpyrifos Oxon Is Associated with Paraoxonase 1 (PON1) Modulated Effects in Maternal and Fetal Tissues

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    Co, Aila L.; Hay, Ariel M.; MacDonald, James W.; Bammler, Theo K.; Farin, Federico M.; Costa, Lucio G.; Furlong, Clement E.

    2014-01-01

    Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP) insecticide chlorpyrifos, causes developmental neurotoxicity in humans and rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by PON1 levels and the human Q192R polymorphism. To examine how the Q192R polymorphism influences fetal toxicity associated with gestational CPO exposure, we measured enzyme inhibition and fetal-brain gene expression in wild-type (PON1+/+), PON1-knockout (PON1−/−), and tgHuPON1R192 and tgHuPON1Q192 transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75, or 0.85 mg/kg/d CPO from gestational day (GD) 6 through 17 were sacrificed on GD18. Biomarkers of CPO exposure inhibited in maternal tissues included brain acetylcholinesterase (AChE), red blood cell acylpeptide hydrolase (APH), and plasma butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was inhibited in PON1−/− and tgHuPON1Q192, but not PON1+/+ or tgHuPON1R192 mice. Fetal brain AChE and plasma CES were inhibited in PON1−/− mice, but not in other genotypes. Weighted gene co-expression network analysis identified five gene modules based on clustering of the correlations among their fetal-brain expression values, allowing for correlation of module membership with the phenotypic data on enzyme inhibition. One module that correlated highly with maternal brain AChE activity had a large representation of homeobox genes. Gene set enrichment analysis revealed multiple gene sets affected by gestational CPO exposure in tgHuPON1Q192 but not tgHuPON1R192 mice, including gene sets involved in protein export, lipid metabolism, and neurotransmission. These data indicate that maternal PON1 status modulates the effects of repeated gestational CPO exposure on fetal-brain gene expression and on inhibition of both maternal and fetal biomarker enzymes. PMID:25070982

  17. Paraoxonase 1 activity and genotyping in systemic lupus ...

    African Journals Online (AJOL)

    Introduction: Systemic lupus erythematosus (SLE) is characterized by an enhanced risk of atherosclerosis and cardiovascular diseases (CVD). Human serum paraoxonase 1 (PON1), an antioxidant enzyme closely associated with high density lipoprotein (HDL), has been implicated in the prevention of low density ...

  18. Purification of PON1 from human serum and assessment of enzyme kinetics against metal toxicity.

    Science.gov (United States)

    Ekinci, Deniz; Beydemir, Sükrü

    2010-06-01

    Paraoxonase-1 (PON1) is an organophosphate hydrolyser enzyme which has also antioxidant properties in metabolism. Due to its crucial functions, inhibition of the enzyme is undesirable and very dangerous. PON1 enzyme activity should not be altered in any case. Inhibitory investigations of this enzyme are therefore important and useful. Metal toxicology of enzymes has become popular in the recent years. Here, we report the in vitro inhibitory effects of some metal ions, including Pb(+2), Cr(+2), Fe(+2), and Zn(+2), on the activity of human serum PON1 (hPON1; EC 3.1.8.1.). For this purpose, we purified the enzyme from human serum and analyzed the alterations in the enzyme activity in the presence of metal ions. The results show that metal ions exhibit inhibitory effects on hPON1 at low concentrations with IC (50) values ranging from 0.838 to 7.410 mM. Metal ions showed different inhibition mechanisms: lead and iron were competitive, chrome was noncompetitive, and zinc was uncompetitive. Lead was determined to be the most effective inhibitor.

  19. Pig PON1

    DEFF Research Database (Denmark)

    Larsen, Knud Erik; Farajzadeh, Leila; Kristensen, Kaja Kjaer

    2018-01-01

    Atherosclerosis is an inflammatory disease promoted by oxidized low density lipoprotein (LDL). High density lipoprotein (HDL) is an important antioxidant, protecting LDL and itself from oxidation and by detoxifying the hydroperoxides from oxidized LDL. Paraoxonase, encoded by the PON1 gene......, is an enzyme involved in oxidant defense by hydrolyzing oxidized lipids, including oxLDL, and in detoxification of organophosphate pesticides. Aging is the major risk factor for developing atherosclerosis and as paraoxonase is responsible for the antioxidant effect of HDL, aging might be accompanied...

  20. Serum paraoxonase-1 gene polymorphism and enzyme activity in patients with urolithiasis.

    Science.gov (United States)

    Atar, Arda; Gedikbasi, Asuman; Sonmezay, Erkan; Kiraz, Zeynep Kusku; Abbasoglu, Semra; Tasci, Ali Ihsan; Tugcu, Volkan

    2016-01-01

    Paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. PON1 has two genetic polymorphisms both due to amino acid substitution, one involving glutamine and arginine at position 192 and the other leucine and methionine at position 55. Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. Our study aimed to compare the effects of PON1 192, PON1 55 polymorphisms, and PON1 activity in patients with urolithiasis and controls. PON1's arylesterase/paraoxonase activities and phenotype were determined in 158 stone forming cases (Group 1) and 138 non-stone forming controls (Group 2). The PON1 192 and PON1 55 polymorphisms were studied by polymerase chain reaction/restriction fragment length polymorphism. Paraoxonase activity was significantly lower in Group 1 than Group 2 (112 ± 31.8 vs. 208 ± 53.1 IU/L) (p < 0.001). The PON1 L55M polymorphism was significantly higher in Group 1. The "M" allele coding for PON1 was higher in Group 1 (p < 0.001). PON1 192 RR homozygotes had significantly higher PON1 activity than QR and QQ genotypes among all the patients (p < 0.001). The results of our study demonstrate that the PON1 55 gene "M" allele is associated with renal stone disease. Individuals possessing the "M" allele have a higher incidence of urolithiasis. The results of this study provide genetic evidence that the PON1 gene may play a role in stone formation. PON1 genotype determination may provide a tool to identify individuals who are at risk of urolithiasis.

  1. Paraoxonase 1 Activity in Endocrine Diseases

    OpenAIRE

    Özlem Tarçın; Dilek Gogas Yavuz

    2011-01-01

    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 ...

  2. Oxidative status and serum PON1 activity in beta-thalassemia minor.

    Science.gov (United States)

    Selek, Sahbettin; Aslan, Mehmet; Horoz, Mehmet; Gur, Mustafa; Erel, Ozcan

    2007-03-01

    Paraoxonase-1 (PON1) deficiency is related to increased susceptibility to low density lipoprotein oxidation and development of atherosclerosis. The aim of this study was to investigate paraoxonase and arylesterase activities along with oxidative status parameters, and to find out if there is any increased susceptibility to atherogenesis, which might be reflected with increased oxidative stress and decreased serum PON1 activity in beta-thalassemia minor (BTM) subjects. Thirty-two subjects with BTM and 28 healthy subjects as control were enrolled in the study. Serum paraoxonase and arylesterase activities, lipid hydroperoxide (LOOH) levels, total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined. Serum TAC, paraoxonase and arylesterase activities were significantly lower in BTM subjects than controls (for all p<0.001), while TOS, LOOH levels and OSI were significantly higher (p<0.001, p<0.05 and p<0.001; respectively). In BTM subjects, OSI, TOS, LOOH levels and TAC were significantly correlated with serum paraoxonase (r=-0.245, p<0.05; r=-0.231, p<0.05; r=-0.264, p<0.05 and, r=0.342, p<0.05, respectively) and arylesterase activities (r=-0.332, p<0.05, r=-0.308, p<0.05; r=-0.320, p<0.05 and r=0.443, p<0.05). Additionally, hemoglobin level was also correlated with serum paraoxonase (r=0.501, p<0.001) and arylesterase activities (r=0.501, p<0.001), TAC (r=0.402, p<0.05), TOS (r=-0.274, p<0.05) and OSI (r=-0.352, p<0.05). Oxidative stress is increased, while serum PON1 activity is decreased in BTM subjects. Decrease in PON1 activity seems to be associated with both the degree of oxidative stress and anemia. BTM subjects may be more prone to development of atherogenesis due to low serum PON1 activity.

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

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    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.

  4. Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS?

    Science.gov (United States)

    Dursun, Polat; Demirtaş, Ezgi; Bayrak, Ahmet; Yarali, Hakan

    2006-01-01

    Patients with polycystic ovary syndrome (PCOS) may have an increased risk for the development of hypertension and atherosclerotic heart disease (AHD), the pathophysiological mechanisms of which are not clear. Paraoxonase1 (PON1) is a high-density lipoprotein-associated enzyme that prevents oxidative modification of low-density lipoprotein. The aim of this study was to measure the serum levels of PON1 activity in patients with PCOS and to compare with those of regularly cycling controls. Serum lipid parameters, malondialdehyde (MDA) levels and PON1 activity, were measured in PCOS patients (n = 23) and regularly cycling, age-, body mass index- and smoking status-matched controls (n = 23). All patients had normal glucose tolerance test as assessed by a 75 g oral glucose tolerance test. None of the patients had clinically evident hypertension or AHD. Apart from the mean serum PON1 activity, all parameters in the lipid profile including serum MDA levels were comparable between the two groups. There were no significant differences in respect to fasting glucose (4.64 +/- 0.5 versus 4.43 +/- 0.83 mmol/l) and fasting glucose insulin ratio (11.06 +/- 8.26 versus 11.49 +/- 4.90) among the two groups (P > 0.05). However, HOMA insulin resistance index was significantly higher in patients with PCOS compared with the controls (2.06 +/- 0.86 versus 1.51 +/- 0.49; P = 0.01). Also, mean serum PON1 activity was significantly lower in the PCOS group compared with the controls (151.2 +/- 90.8 versus 217.7 +/- 101.6, respectively; P = 0.027). Reduced serum PON1 activity might contribute to the increased susceptibility for the development of AHD in women with PCOS.

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

    International Nuclear Information System (INIS)

    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

    2011-01-01

    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 ± 42.32 nmol/min/ml in controls) and phenylacetate (112.74 ± 17.37 vs. 134.28 ± 25.49 μmol/min/ml in controls) was significantly lower in workers than in control subjects (p 192 QR (Gln/Arg) and PON1 55 LM (Leu/Met) in workers and control subjects (p > 0.05). 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 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

  6. The Q192R polymorphism of the paraoxonase-1 (PON1) gene is associated with susceptibility to gestational diabetes mellitus in the Greek population.

    Science.gov (United States)

    Pappa, Kalliopi I; Gazouli, Maria; Anastasiou, Eleni; Loutradis, Dimitrios; Anagnou, Nicholas P

    2017-08-01

    A key factor protecting from oxidative stress in gestational diabetes mellitus (GDM) and in type 2 diabetes (T2D) is paraoxonase-1 (PON1). Inconclusive and limited data exist regarding the effect of a coding polymorphism (Q192R) of the PON1 gene in conferring susceptibility to both states. In the present study, we investigated the association between the PON1 gene and the risk for GDM in the Greek population and assessed for the first time its transcriptional efficiency. We studied 185 women with GDM and 104 non-diabetic controls for the PON1 polymorphism. For PON1 mRNA expression, peripheral leucocytes were harvested from 20 GDM and 20 control women, harboring different genotypes for the polymorphism, using real-time quantitative PCR. The RR genotype and the R allele of the PON1 Q192R polymorphism were significantly associated with an increased risk for GDM (p = 0.012 and p < 0.0001, respectively). Furthermore, there was no statistical correlation between the individual metabolic parameters tested and the three genotypes. Finally, the expression levels of PON1 mRNA in GDM patients did not exhibit any statistical difference compared with normal controls (p = 0.138). These data independently document that the Q192R polymorphism is closely associated with GDM susceptibility, while the PON1 gene expression is not impaired in GDM.

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

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    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.

  8. 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

    2017-08-01

    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.

  9. 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.

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

    International Nuclear Information System (INIS)

    Giordano, Gennaro; Cole, Toby B.; Furlong, Clement E.; Costa, Lucio G.

    2011-01-01

    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 −/− ] 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 2 O 2 ) was higher in cells from PON2 −/− 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.

  11. Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus

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    Manzi Susan

    2011-01-01

    Full Text Available Abstract Background Low serum paraoxonase (PON activity is associated with the risk of coronary artery disease, diabetes and systemic lupus erythematosus (SLE. Our prior studies have shown that the PON1/rs662 (p.Gln192Arg, PON1/rs854560 (p.Leu55Met, PON3/rs17884563 and PON3/rs740264 SNPs (single nucleotide polymorphisms significantly affect serum PON activity. Since PON1, PON2 and PON3 share high degree of structural and functional properties, in this study, we examined the role of PON2 genetic variation on serum PON activity, risk of SLE and SLE-related clinical manifestations in a Caucasian case-control sample. Methods PON2 SNPs were selected from HapMap and SeattleSNPs databases by including at least one tagSNP from each bin defined in these resources. A total of nineteen PON2 SNPs were successfully genotyped in 411 SLE cases and 511 healthy controls using pyrosequencing, restriction fragment length polymorphism (RFLP or TaqMan allelic discrimination methods. Results Our pair-wise linkage disequilibrium (LD analysis, using an r2 cutoff of 0.7, identified 14 PON2 tagSNPs that captured all 19 PON2 variants in our sample, 12 of which were not in high LD with known PON1 and PON3 SNP modifiers of PON activity. Stepwise regression analysis of PON activity, including the known modifiers, identified five PON2 SNPs [rs6954345 (p.Ser311Cys, rs13306702, rs987539, rs11982486, and rs4729189; P = 0.005 to 2.1 × 10-6] that were significantly associated with PON activity. We found no association of PON2 SNPs with SLE risk but modest associations were observed with lupus nephritis (rs11981433, rs17876205, rs17876183 and immunologic disorder (rs11981433 in SLE patients (P = 0.013 to 0.042. Conclusions Our data indicate that PON2 genetic variants significantly affect variation in serum PON activity and have modest effects on risk of lupus nephritis and SLE-related immunologic disorder.

  12. 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.

  13. 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

  14. Low Serum Paraoxonase-1 Lactonase and Arylesterase Activities in Obese Children and Adolescents

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    Sandor Raluca

    2015-12-01

    Full Text Available Serum paraoxonase-1 (PON1 binds mainly to high density lipoproteins (HDLs and protects low density lipoproteins (LDLs against oxidation. While paraoxonase and arylesterase activities are traditionally assayed, lactonase activity, accounting for protection against LDL oxidation, was less investigated in obese children and adolescents. Therefore, we aimed to measure lactonase, paraoxonase and arylesterase activities, oxidized LDL (ox-LDL and malondialdehyde (MDA levels in obese children and adolescents.

  15. Human Paraoxonase1 Hydrolysis of Nanomolar Chlorpyrifos-oxon Concentrations is Unaffected by Phenotype or Q192R Genotype

    Science.gov (United States)

    Coombes, R. Hunter; Meek, Edward C.; Dail, Mary Beth; Chambers, Howard W.; Chambers, Janice E.

    2016-01-01

    The organophosphorus insecticide chlorpyrifos has been widely used. Its active metabolite chlorpyrifos-oxon (CPO) is a potent anticholinesterase and is detoxified by paraoxonase-1 (PON1). PON1 activity is influenced by numerous factors including a Q192R polymorphism. Using forty human blood samples bearing homozygous genotypes and either high or low activity phenotypes (as determined by high concentration assays of paraoxon and diazoxon hydrolysis) the serum PON1 hydrolysis of high (320 μM) and low (178 nM) CPO concentrations was assessed using direct or indirect spectrophotometric methods, respectively. PON1 activity at high CPO concentration reflected the phenotype and genotype differences; subjects with the high activity phenotype and homozygous for the PON1R192 alloform hydrolyzed significantly more CPO than subjects with the low activity phenotype and/or PON1Q192 alloform (High RR=11023±722, Low RR=9467±798, High QQ=8809±672, Low QQ=6030±1015 μmoles CPO hydrolyzed/min/L serum). However, PON1 hydrolysis of CPO at the lower, more environmentally relevant concentration showed no significant differences between the PON1192 genotypes and/or between high and low activity phenotypes (High RR=231±27, Low RR=219±52, High QQ=193±59, Low QQ=185±43 nmoles CPO/min/L serum). Low CPO concentrations were probably not saturating, so PON1 did not display maximal velocity and the PON1 genotype/phenotype might not influence the extent of metabolism at environmental exposures. PMID:25093614

  16. Paraoxonase 1 Q192R (PON1-192) polymorphism is associated with reduced lipid peroxidation in healthy young men on a low-carotenoid diet supplemented with tomato juice.

    Science.gov (United States)

    Bub, Achim; Barth, Stephan W; Watzl, Bernhard; Briviba, Karlis; Rechkemmer, Gerhard

    2005-03-01

    The HDL-bound enzyme paraoxonase (PON) protects LDL from oxidation and may therefore attenuate the development of atherosclerosis. We examined the effect of tomato and carrot juice consumption on PON1 activity and lipid peroxidation in healthy young volunteers with different PON1-192 genotypes (Q/R substitution at position 192). In this randomized cross-over study twenty-two healthy, non-smoking men on a low-carotenoid diet received 330 ml/d tomato juice (37.0 mg lycopene, 1.6 mg beta-carotene) or carrot juice (27.1 mg beta-carotene, 13.1 mg alpha-carotene) for 2 weeks. Intervention periods were preceded by 2-week low-carotenoid intake. We determined the PON1-192 genotype by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) and measured ex vivo LDL oxidation (lag time), plasma malondialdehyde and PON1 activity at the beginning and end of each intervention period. At baseline, lag time was higher (Pjuice consumption had significant effects on PON1 activity. However, tomato juice consumption reduced (Pjuice had no significant effect on malondialdehyde irrespective of the PON1-192 genotype. Male volunteers with the QR/RR genotype showed an increased lipid peroxidation at baseline. Although tomato and carrot juice fail to affect PON1 activity, tomato juice intake reduced lipid peroxidation in healthy volunteers carrying the R-allele of the PON1-192 genotype and could thus contribute to CVD risk reduction in these individuals.

  17. Paraoxonase-2 and paraoxonase-3: comparison of mRNA expressions in the placentae of unexplained intrauterine growth restricted and noncomplicated pregnancies.

    Science.gov (United States)

    Dikbas, Levent; Yapca, Omer Erkan; Dikbas, Neslihan; Gundogdu, Cemal

    2017-05-01

    Recent evidence suggests that oxidative stress is involved in the pathophysiology of many human diseases. It has been demonstrated that oxidative stress is associated with intrauterine growth restriction (IUGR), and the depletion of placental antioxidant systems has been suggested as a key factor in this disease. Our aims were to explore the possible role of antioxidant paraoxonase-2 (PON2) and paraoxonase-3 (PON3) in the pathophysiology of unexplained IUGR. We have studied the expression of mRNA for PON2, PON3 in placental tissues by using RT-qPCR. Two groups, consisting of normal (n = 18) and unexplained IUGR pregnancies (n = 20) were compared. Our results demonstrated that there were no significant differences in the mRNA expressions of PON2, PON3 between the two groups (p = 0.28, p = 0.90, respectively). PON2 and PON3 were down-regulated in IUGR. Antenatal steroid therapy had no effect on the expression mRNA in placentae of unexplained IUGR pregnancies compared to non-treated group. These results suggest that PON2, PON3 mRNA levels were not changed significantly in placentae of IUGR when compared to normal pregnant women.

  18. Paraoxonase 1 Phenotype and Mass in South Asian versus Caucasian Renal Transplant Recipients

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    Philip W. Connelly

    2012-01-01

    Full Text Available South Asian renal transplant recipients have a higher incidence of cardiovascular disease compared with Caucasian renal transplant recipients. We carried out a study to determine whether paraoxonase 1, a novel biomarker for cardiovascular risk, was decreased in South Asian compared with Caucasian renal transplant recipients. Subjects were matched two to one on the basis of age and sex for a total of 129 subjects. Paraoxonase 1 was measured by mass, arylesterase activity, and two-substrate phenotype assay. Comparisons were made by using a matched design. The frequency of PON1 QQ, QR and RR phenotype was 56%, 37%, and 7% for Caucasian subjects versus 35%, 44%, and 21% for South Asian subjects (χ2=7.72, P=0.02. PON1 mass and arylesterase activity were not significantly different between South Asian and Caucasian subjects. PON1 mass was significantly associated with PON1 phenotype (P=0.0001, HDL cholesterol (P=0.009, LDL cholesterol (P=0.02, and diabetes status (P<0.05. Arylesterase activity was only associated with HDL cholesterol (P=0.003. Thus the frequency of the PON1 RR phenotype was higher and that of the QQ phenotype was lower in South Asian versus Caucasian renal transplant recipients. However, ethnicity was not a significant factor as a determinant of PON1 mass or arylesterase activity, with or without analysis including PON1 phenotype. The two-substrate method for determining PON1 phenotype may be of value for future studies of cardiovascular complications in renal transplant recipients.

  19. Paraoxonase 1 Phenotype and Mass in South Asian versus Caucasian Renal Transplant Recipients.

    Science.gov (United States)

    Connelly, Philip W; Maguire, Graham F; Nash, Michelle M; Rapi, Lindita; Yan, Andrew T; Prasad, G V Ramesh

    2012-01-01

    South Asian renal transplant recipients have a higher incidence of cardiovascular disease compared with Caucasian renal transplant recipients. We carried out a study to determine whether paraoxonase 1, a novel biomarker for cardiovascular risk, was decreased in South Asian compared with Caucasian renal transplant recipients. Subjects were matched two to one on the basis of age and sex for a total of 129 subjects. Paraoxonase 1 was measured by mass, arylesterase activity, and two-substrate phenotype assay. Comparisons were made by using a matched design. The frequency of PON1 QQ, QR and RR phenotype was 56%, 37%, and 7% for Caucasian subjects versus 35%, 44%, and 21% for South Asian subjects (χ(2) = 7.72, P = 0.02). PON1 mass and arylesterase activity were not significantly different between South Asian and Caucasian subjects. PON1 mass was significantly associated with PON1 phenotype (P = 0.0001), HDL cholesterol (P = 0.009), LDL cholesterol (P = 0.02), and diabetes status (P < 0.05). Arylesterase activity was only associated with HDL cholesterol (P = 0.003). Thus the frequency of the PON1 RR phenotype was higher and that of the QQ phenotype was lower in South Asian versus Caucasian renal transplant recipients. However, ethnicity was not a significant factor as a determinant of PON1 mass or arylesterase activity, with or without analysis including PON1 phenotype. The two-substrate method for determining PON1 phenotype may be of value for future studies of cardiovascular complications in renal transplant recipients.

  20. 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.

  1. Genetic polymorphisms and activity of PON1 in a Mexican population

    International Nuclear Information System (INIS)

    Rojas-Garcia, A.E.; Solis-Heredia, M.J.; Pina-Guzman, B.; Vega, L.; Lopez-Carrillo, L.; Quintanilla-Vega, B.

    2005-01-01

    Human paraoxonase (PON1) plays a role in detoxification of organophosphorus (OP) compounds by hydrolyzing the bioactive oxons, and in reducing oxidative low-density lipoproteins, which may protect against atherosclerosis. Some PON1 polymorphisms have been found to be responsible for variations in catalytic activity and expression and have been associated with susceptibility to OP poisoning and vascular diseases. Both situations are of public health relevance in Mexico. Therefore, the aim of this study was to evaluate PON1 phenotype and the frequencies of polymorphisms PON1 -162, -108, 55, and 192 in a Mexican population. The studied population consisted of unrelated individuals (n = 214) of either gender, 18-52 years old. Serum PON1 activity was assayed using phenylacetate and paraoxon as substrates. PON1 variants, -162, 55, and 192, were determined by real-time PCR using the TaqMan System, and PON1 -108 genotype by PCR-RFLP. We found a wide interindividual variability of PON1 activity with a unimodal distribution; the range of enzymatic activity toward phenylacetate was 84.72 to 422.0 U/mL, and 88.37 to 1645.6 U/L toward paraoxon. All four PON1 polymorphisms showed strong linkage disequilibrium (D% >90). PON1 polymorphisms -108, 55, and 192 were independently associated with arylesterase activity; whereas the activity toward paraoxon was related only with PON1 192 polymorphism, suggesting that this polymorphism is determinant to infer PON1 activity. A better understanding of the phenotype and genotypes of PON1 in Mexican populations will facilitate further epidemiological studies involving PON1 variability in OP poisoning and in the development of atherosclerosis

  2. Paraoxonase Enzyme Protects Retinal Pigment Epithelium from Chlorpyrifos Insult

    Science.gov (United States)

    Jasna, Jagan Mohan; Anandbabu, Kannadasan; Bharathi, Subramaniam Rajesh; Angayarkanni, Narayanasamy

    2014-01-01

    Retinal pigment epithelium (RPE) provides nourishment and protection to the eye. RPE dysfunction due to oxidative stress and inflammation is one of the major reason for many of the retinal disorders. Organophosphorus pesticides are widely used in the agricultural, industrial and household activities in India. However, their effects on the eye in the context of RPE has not been studied. In this study the defense of the ARPE19 cells exposed to Chlorpyrifos (1 nM to 100 µM) in terms of the enzyme paraoxonase (PON) was studied at 24 hr and 9 days of treatment. Chlorpyrifos was found to induce oxidative stress in the ARPE19 cells as seen by significant increase in ROS and decrease in glutathione (GSH) levels without causing cell death. Tissue resident Paraoxonase 2 (PON2) mRNA expression was elevated with chlorpyrifos exposure. The three enzymatic activities of PON namely, paraoxonase (PONase), arylesterase (PON AREase) and thiolactonase (PON HCTLase) were also found to be significantly altered to detoxify and as an antioxidant defense. Among the transcription factors regulating PON2 expression, SP1 was significantly increased with chlorpyrifos exposure. PON2 expression was found to be crucial as ARPE19 cells showed a significant loss in their ability to withstand oxidative stress when the cells were subjected to chlorpyrifos after silencing PON2 expression. Treatment with N-acetyl cysteine positively regulated the PON 2 expression, thus promoting the antioxidant defense put up by the cells in response to chlorpyrifos. PMID:24979751

  3. PON1 and Mediterranean Diet

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    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.

  4. PON1 polymorphisms are associated with polycystic ovary syndrome susceptibility, related traits, and PON1 activity in Indian women with the syndrome.

    Science.gov (United States)

    Dadachanji, Roshan; Shaikh, Nuzhat; Khavale, Sushma; Patil, Anushree; Shah, Nalini; Mukherjee, Srabani

    2015-07-01

    To investigate the association of paraoxonase 1 (PON1) polymorphisms (L55M and Q192R) with polycystic ovary syndrome (PCOS) susceptibility and its related traits in Indian women. Case-control study. Academic research institute, infertility, and endocrinology clinics. Controls (n = 326), women with PCOS (n = 482). None. Genotypic and allelic frequency distribution, genotype-phenotype association, different PON1 activities (lactonase, arylesterase, and paraoxonase). The genotypic and allelic frequency distributions of the L55M polymorphism were significantly different between lean controls and lean women with PCOS, and this polymorphism reduced the risk of PCOS development in lean but not in obese Indian women. Furthermore, this polymorphism was significantly associated with decreased 2-hour glucose, apolipoprotein B, free and bioavailable T, and free androgen index concurrent with increased sex hormone-binding globulin (SHBG) and FSH levels only in lean women with PCOS. However, Q192R polymorphism showed comparable genotypic frequency distribution between controls and women with PCOS. PON1 lactonase and arylesterase activities were significantly decreased in women with PCOS compared with controls. PON1 polymorphisms were shown to influence its activities. Our study showed that L55M, but not Q192R, polymorphism is significantly associated with reduced PCOS susceptibility only in lean women and also impacts glucose metabolism, lipid parameters, and hyperandrogenemia in them. Our study therefore suggests the possibility of differential genetic pathophysiology of PCOS between lean and obese women. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Interaction between organophosphate pesticide exposure and PON1 activity on thyroid function

    International Nuclear Information System (INIS)

    Lacasana, Marina; Lopez-Flores, Inmaculada; Rodriguez-Barranco, Miguel; Aguilar-Garduno, Clemente; Blanco-Munoz, Julia; Perez-Mendez, Oscar; Gamboa, Ricardo; Gonzalez-Alzaga, Beatriz; Bassol, Susana; Cebrian, Mariano E.

    2010-01-01

    Organophosphate pesticides are widely used in agricultural purposes. Recently, a few studies have demonstrated the ability of these chemicals to alter the function of the thyroid gland in human. Moreover, the paraoxonase-1 enzyme (PON1) plays an important role in the toxicity of some organophosphate pesticides, with low PON1 activity being associated with higher pesticide sensitivity. This study evaluates the interaction between exposure to organophosphate compounds and PON1 enzyme activity on serum levels of TSH and thyroid hormones in a population of workers occupationally exposed to pesticides. A longitudinal study was conducted on a population of floriculture workers from Mexico, during two periods of high and low-intensity levels of pesticide application. A structured questionnaire was completed by workers containing questions on sociodemographic characteristics and other variables of interest. Urine and blood samples were taken, and biomarkers of exposure (dialkylphosphates), susceptibility (PON1 polymorphisms and activity) and effect (thyroid hormone levels) were determined. Interaction between dialkylphosphates and PON1 polymorphisms or PON1 activity on hormone levels was evaluated by generalized estimating equation (GEE) models. A significant interaction was found between serum diazoxonase activity and total dialkylphosphates (ΣDAP) on TSH levels. Thus, when PON1 activity was increased we observed a decrease in the percentage of variation of TSH level for each increment in one logarithmic unit of the ΣDAP levels. This interaction was also observed with the PON1 192 RR genotype. These results suggest a stronger association between organophosphate pesticides and thyroid function in individuals with lower PON1 activity.

  6. Serum paraoxonase-1 as biomarker for improved diagnosis of fatty liver in dairy cows.

    Science.gov (United States)

    Farid, Ayman Samir; Honkawa, Kazuyuki; Fath, Eman Mohamed; Nonaka, Nariaki; Horii, Yoichiro

    2013-04-11

    Fatty liver is a major metabolic disorder in dairy cows and is believed to result in major economic losses in dairy farming due to decreased health status, reproductive performance and fertility. Currently, the definitive means for diagnosing fatty liver is determining the fat content of hepatic tissue by liver biopsy, which is an invasive and costly procedure, making it poorly suited to dairy farms. Therefore, the key aim of this study was to investigate the measurement of serum paraoxonase-1 (PON1), an enzyme exclusively synthesized by the liver, as a sensitive noninvasive biomarker for diagnosis of fatty liver in dairy cows. A comparative cohort study using serum specimens from Holstein-Friesian dairy cows (46 healthy and 46 fatty liver cases) was conducted. Serum PON1 (paraoxonase, lactonase and arylesterase) activity and other biochemical and hematological parameters were measured. We found that serum PON1 activity was lower (Pratio (+LR), negative likelihood ratio (-LR), diagnostic odd ratio (DOR) and overall diagnostic accuracy in diagnosing fatty liver. The present results indicate that addition of serum PON1 activity measurement to the biochemical profile could improve the diagnosis of fatty liver in dairy cows, which would have a considerable clinical impact and lead to greater profitability in the dairy industry.

  7. Longitudinal changes in PON1 enzymatic activities in Mexican-American mothers and children with different genotypes and haplotypes

    International Nuclear Information System (INIS)

    Huen, Karen; Harley, Kim; Bradman, Asa; Eskenazi, Brenda; Holland, Nina

    2010-01-01

    The paraoxonase 1 (PON1) enzyme prevents low-density lipoprotein oxidation and also detoxifies the oxon derivatives of certain neurotoxic organophosphate (OP) pesticides. PON1 activity in infants is low compared to adults, rendering them with lower metabolic and antioxidant capacities. We made a longitudinal comparison of the role of genetic variability on control of PON1 phenotypes in Mexican-American mothers and their children at the time of delivery (n = 388 and 338, respectively) and again 7 years later (n = 280 and 281, respectively) using generalized estimating equations models. At age 7, children's mean PON1 activities were still lower than those of mothers. This difference was larger in children with genotypes associated with low PON1 activities (PON1 -108TT , PON1 192QQ , and PON1 -909CC ). In mothers, PON1 activities were elevated at delivery and during pregnancy compared to 7 years later when they were not pregnant (p < 0.001). In non-pregnant mothers, PON1 polymorphisms and haplotypes accounted for almost 2-fold more variation of arylesterase (AREase) and chlorpyrifos-oxonase (CPOase) activity than in mothers at delivery. In both mothers and children, the five PON1 polymorphisms (192, 55, -108, -909, -162) explained a noticeably larger proportion of variance of paraoxonase activity (62-78%) than AREase activity (12.3-26.6%). Genetic control of PON1 enzymatic activity varies in children compared to adults and is also affected by pregnancy status. In addition to known PON1 polymorphisms, unidentified environmental, genetic, or epigenetic factors may also influence variability of PON1 expression and therefore susceptibility to OPs and oxidative stress.

  8. ASSOCIATION BETWEEN THE SEVERITY OF ANGIOGRAPHIC CORONARY ARTERY DISEASE AND PARAOXONASE-1 PROMOTER GENE POLYMORPHISM T(-107C IN IRANIAN POPULATION

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    A. Jalilian

    2008-06-01

    Full Text Available The oxidation of low-density lipoproteins and cell membrane lipids is believed to play an integral role in the development of fatty streak lesions, an initial step in coronary artery disease (CAD. Paraoxonase-1 (PON1 is an enzyme associated with the high-density lipoprotein (HDL particle. PON1 protects LDL from oxidative modification by hydrolyzing lipid peroxides, suggestive of a role for PON1 in the development of CAD. The present study tested the hypothesis that Paraoxonase-1 promoter polymorphism T(-107C could be a risk factor for severity of CAD in Iranian population. Paraoxonase-1 promoter genotypes were determined in 300 consecutive subjects (> 40 years old who underwent coronary angiography (150 subjects with >50% stenosis served as cases [CAD+] and 150 subjects with < 20% stenosis served as controls [CAD-]. PON1 promoter genotypes were determined by PCR and BSTU1 restriction enzyme digestion. CAD+ Subjects did not show any significant differences in the distribution of PON1 promoter genotypes as compared to CAD- Subjects (P = 0.075. However the analysis of PON1 promoter genotypes distribution showed a higher percentage of (-107 TT among CAD+ compared with CAD- (P = 0.027. After controlling for other risk factors, the T(-107C polymorphism had interaction with age (P = 0.012, but did not show any interaction with other risk factors such as BMI ,gender, smoking, diabetes, level of HDL-C, LDL-C, triglyceride and Total cholesterol. These data suggest that the TT genotype may represent a genetic risk factor for Coronary artery disease in Iranian population.

  9. Paraoxonase1 Genetic Polymorphisms in a Mixed Ancestry African Population

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    M. Macharia

    2014-01-01

    Full Text Available Paraoxonase 1 (PON1 activity is markedly influenced by coding polymorphisms, Q/R at position 192 and M/L at position 55 of the PON1 gene. We investigated the frequencies of these polymorphisms and their effects on PON1 and antioxidant activities in 844 South African mixed ancestry individuals. Genotyping was done using allele-specific TaqMan technology, PON1 activities were measured using paraoxon and phenylacetate, oxidative status was determined by measuring the antioxidant activities of ferric reducing antioxidant power and trolox equivalent antioxidant capacity, and lipid peroxidation markers included malondialdehyde and oxidized LDL. The frequencies of Q192R and L55M were 47.6% and 28.8%, respectively, and the most common corresponding alleles were 192R (60.4% and 55M (82.6%. The Q192 was significantly associated with 5.8 units’ increase in PON1 concentration and 15.4 units’ decrease in PONase activity after adjustment for age, sex, BMI, and diabetes, with suggestion of differential effects by diabetes status. The PON1 L55 variant was associated with none of the measured indices. In conclusion, we have shown that the Q192R polymorphism is a determinant of both PON1 concentration and activity and this association appeared to be enhanced in subjects with diabetes.

  10. Effect of rosuvastatin versus atorvastatin treatment on paraoxonase-1 activity in men with established cardiovascular disease and a low HDL-cholesterol

    NARCIS (Netherlands)

    Bergheanu, S. C.; van Tol, A.; Dallinga-Thie, G. M.; Liem, A.; Dunselman, P. H. J.; Van Der Bom, J. G.; Jukema, J. W.

    Objective: Paraoxonase-1 (PON-1) is a highdensity lipoprotein (HDL) associated enzyme involved in the protective mechanisms of HDL. Our aim was to compare the effect of treatment with rosuvastatin and atorvastatin on serum PON-1 activity. Methods: We performed a prespecif ied prospective study in 68

  11. Paraoxonase-1 L55M polymorphism with fatty acid composition of phospholipids in high-density lipoproteins

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    Ghatreh Samani K

    2012-04-01

    Conclusion: Allele (L from L55M polymorphism had a higher frequency in patients with higher LDL-C concentrations. PON1 genotypes seemed to have a modifying role on paraoxonase-1 activity after lovastatin therapy.

  12. Effect of rosuvastatin versus atorvastatin treatment on paraoxonase-1 activity in men with established cardiovascular disease and a low HDL-cholesterol

    NARCIS (Netherlands)

    Bergheanu, S. C.; van Tol, A.; Dallinga-Thie, G. M.; Liem, A.; Dunselman, P. H. J.; van der Bom, J. G.; Jukema, J. W.

    2007-01-01

    Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL) associated enzyme involved in the protective mechanisms of HDL. Our aim was to compare the effect of treatment with rosuvastatin and atorvastatin on serum PON-1 activity. We performed a prespecified prospective study in 68 patients, part of a

  13. 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...

  14. Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3 Protein Levels in Human-Derived Liver (HepG2) Cells.

    Science.gov (United States)

    Sayılan Özgün, Gülben; Özgün, Eray; Tabakçıoğlu, Kıymet; Süer Gökmen, Selma; Eskiocak, Sevgi; Çakır, Erol

    2017-12-01

    Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 are antioxidant and anti-atherosclerotic structural high-density lipoprotein proteins that are mainly synthesized by the liver. No study has ever been performed to specifically examine the effects of caffeine on paraoxonase enzymes and on liver apolipoprotein A-1 protein levels. To investigate the dose-dependent effects of caffeine on liver apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels. In vitro experimental study. HepG2 cells were incubated with 0 (control), 10, 50 and 200 μM of caffeine for 24 hours. Cell viability was evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels were measured by western blotting. We observed a significant increase on apolipoprotein A-1 and paraoxonase-1 protein levels in the cells incubated with 50 µM of caffeine and a significant increase on paraoxonase-1 protein level in the cells incubated with 200 µM of caffeine. Our study showed that caffeine does not change paraoxonase-3 protein level, but the higher doses used in our study do cause an increase in both apolipoprotein A-1 and paraoxonase-1 protein levels in liver cells.

  15. Paraoxonase lactonase activity (PON-HTLase), asymmetric dimethylarginine (ADMA) and platelet activating factor-acetylhydrolase (PAF-AH) activity in non-obese women with PCOS.

    Science.gov (United States)

    Bayrak, Tulin; Dursun, Polat; Bayrak, Ahmet; Gültekin, Murat; Kolusarı, Ali; Cakır, Erdinç; Ozyurt, Merve; Zeyneloğlu, Hulusi B

    2012-11-01

    Paraoxonase1 (PON1), exhibits both esterase activity (PON1-AREase) and homocysteine thiolactonase activity (PON1-HTLase) which respectively prevent LDL oxidation and detoxify homocysteine thiolactone (HTL). Platelet-activating factor-acetylhydrolase (PAF-AH) is an antioxidant enzyme preventing LDL oxidation by hydrolysis of oxidized phospholipids. Both of these enzymes exhibit a proatherogenic role. ADMA is an endogenous inhibitor of nitric oxide (NO) synthesis causing endothelial dysfunction. The aim was to compare non-obese PCOS patients with a BMI matched control group using the following characteristics: serum PON1-HTLase, ADMA, PAF-AH, and lipid and hormonal parameters. 77 women with PCOS and 25 healthy subject were recruited for this study, The controls were non-obese BMI and age matched with the patients. There were no significant differences with respect to age, BMI, FSH, free testosterone, DHEA, androstenadion, total cholesterol, triglycerides, HDL, LDL, VLDL, fasting glucose/insulin ratio and HOMA-IR among the groups (p > 0.05). However, total testosterone and fasting glucose levels were significantly higher in the PCOS group (p PCOS group while ADMA levels (1.14 ± 0.6 vs. 3.37 ± 6.4, p = 0.004) were significantly higher in the PCOS group. However, there was no significant difference in PAF-AH activity among the groups. Decreased PON1-HTLase and increased ADMA levels might be a relevant marker for the development of future atherosclerotic heart disease (AHD) in non-obese PCOS patients. Further studies are needed to confirm our results.

  16. 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.

  17. Serum paraoxonase 1 activity is associated with fatty acid composition of high density lipoprotein.

    Science.gov (United States)

    Boshtam, Maryam; Razavi, Amirnader Emami; Pourfarzam, Morteza; Ani, Mohsen; Naderi, Gholam Ali; Basati, Gholam; Mansourian, Marjan; Dinani, Narges Jafari; Asgary, Seddigheh; Abdi, Soheila

    2013-01-01

    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. 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. 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 ω 6 fatty acids of HDL. 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.

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

    International Nuclear Information System (INIS)

    Ellison, Corie A.; Crane, Alice L.; Bonner, Matthew R.; Knaak, James B.; Browne, Richard W.; Lein, Pamela J.; Olson, James R.

    2012-01-01

    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.

  19. 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.

  20. The relationship between serum paraoxonase levels and carotid atherosclerotic plaque formation in Alzheimer's patients.

    Science.gov (United States)

    Arslan, Ayşe; Tüzün, Fatma Aykan; Arslan, Harun; Demir, Halit; Tamer, Sibel; Demir, Canan; Tasin, Muhterem

    Low paraoxonase 1 (PON1) activity and carotid atherosclerosis have been suggested to be important risk factors for dementia. However, the studies to date could not fully clarify the relationship between PON1, carotid atherosclerosis and dementia. The present study aimed to measure carotid atherosclerosis and PON1 activity in Alzheimer's Disease and to evaluate the relationship between them. The study included 25 Alzheimer's patients and 25 control subjects, for a total of 50 individuals. The study measured the serum PON1 activity and other biochemical parameters and carotid atherosclerotic plaque values of the participants. The mean paraoxonase activity (31.06±2.31U/L) was significantly lower in the Alzheimer's group compared to the control group (59.05±7.05U/L) (Phomocystein level was higher in the patient group (22.15±7.05) compared to the control group (13.30±3.32). In conclusion, our findings show inverse association between PON1 activity and carotid atherosclerosis in Alzheimer patients: the lower the PON1 activity the more progressed the atherosclerotic process in AD. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Distribution of PON1 polymorphisms PON1Q192R and PON1L55M among Chinese, Malay and Indian males in Singapore and possible susceptibility to organophosphate exposure.

    Science.gov (United States)

    Chia, Sin Eng; Mohamed Ali, Safiyya; Yap, Peng Huat Eric; Gan, Linda; Ong, Yeong Bing; Chia, Kee Seng

    2009-03-01

    Organophosphate (OP)-containing pesticides are widely used worldwide for domestic and industrial purposes. Studies on acute and chronic exposure to OPs have revealed numerous health effects attributed mainly to acetylcholinesterase (AChE) inhibition. The enzyme human serum paraoxonase (PON1) is involved in the detoxification of OP compounds. PON1 polymorphisms have been shown to affect susceptibility to OP exposure. We studied the effect of OP exposure on pest control workers and assessed the distribution of two common PON1 polymorphisms in our local population. The exposed group consisted of 103 workers from various pest control companies under the Singapore Pest Management Association while the 91 unexposed workers were from a lead stabilizer factory. For all workers, the mean age was 36.9 (20-70) years and the ethnic distribution was 38.1% Chinese, 44.3% Malay and 17.5% Indian. The mean+/-S.D. exposure duration among the pesticide workers was 10.4+/-8.4 years. The mean+/-S.D. RBC cholinesterase level was 18436.2+/-2078U/L and 18079.6+/-1576U/L for the exposed and unexposed groups, respectively (p=0.216). The mean+/-S.D. serum pseudocholinesterase was 11028.4+/-2867.4U/L and 9433.6+/-2022.6U/L in the exposed and unexposed groups, respectively (pChinese and Malays (266.5 and 266.3U/L, respectively) whereas that of the Indians was significantly lower (165.6U/L). Our study showed that cholinesterase levels among the exposed were not lower than those in the unexposed group. PON1 polymorphisms differed among ethnic groups, implying that ethnicity could be an important surrogate for identifying susceptible groups in case of OP exposure. Although OP poisoning is rare among occupationally exposed workers in Singapore, this information is useful for other developing countries that have large populations of Chinese, Malays and Indians where OP exposure could be very high especially in agricultural settings.

  3. Association of paraoxonase gene cluster polymorphisms with ALS in France, Quebec, and Sweden.

    Science.gov (United States)

    Valdmanis, P N; Kabashi, E; Dyck, A; Hince, P; Lee, J; Dion, P; D'Amour, M; Souchon, F; Bouchard, J-P; Salachas, F; Meininger, V; Andersen, P M; Camu, W; Dupré, N; Rouleau, G A

    2008-08-12

    The paraoxonase gene cluster on chromosome 7 comprising the PON1-3 genes is an attractive candidate for association in amyotrophic lateral sclerosis (ALS) given the role of paraoxonase genes during the response to oxidative stress and their contribution to the enzymatic break down of nerve toxins. Oxidative stress is considered one of the mechanisms involved in ALS pathogenesis. Evidence for this includes the fact that mutations of SOD1, which normally reduce the production of toxic superoxide anion, account for 12% to 23% of familial cases in ALS. In addition, PON variants were shown to be associated with susceptibility to ALS in several North American and European populations. We extended this analysis to examine 20 single nucleotide polymorphisms (SNPs) across the PON gene cluster in a set of patients from France (480 cases, 475 controls), Quebec (159 cases, 95 controls), and Sweden (558 cases, 506 controls). Although individual SNPs were not considered associated on their own, a haplotype of SNPs at the C-terminal portion of PON2 that includes the PON2 C311S amino acid change was significant in the French (p value 0.0075) and Quebec (p value 0.026) populations as well as all three populations combined (p value 1.69 x 10(-6)). Stratification of the samples showed that this variation was pertinent to ALS susceptibility as a whole, and not to a particular subset of patients. These findings contribute to the increasing weight of evidence that genetic variants in the paraoxonase gene cluster are associated with amyotrophic lateral sclerosis.

  4. Functional paraoxonase 1 variants modify the risk of Parkinson's disease due to organophosphate exposure.

    Science.gov (United States)

    Lee, Pei-Chen; Rhodes, Shannon L; Sinsheimer, Janet S; Bronstein, Jeff; Ritz, Beate

    2013-06-01

    We previously demonstrated that carriers of the "slower metabolizer" MM genotype of paraoxonase (PON1) who were also exposed to ambient organophosphate (OP) pesticides at their residences were at increased risk of developing Parkinson's disease (PD). Here, with a larger sample size, we extend our previous investigation to consider additional sources of ambient exposure and examined two additional functional PON1 variants. From 2001 to 2011, we enrolled incident cases of idiopathic PD and population controls living in central California. We genotyped three well-known functional PON1 SNPs: two exonic polymorphisms (PON1L55M and PON1Q192R) and the promoter region variant (PON1C-108T). Ambient exposures to diazinon, chlorpyrifos, and parathion at residential and workplace addresses were assessed using a validated geographic information system-based model incorporating records of agricultural pesticide applications in California. The odds ratio (OR) for Caucasians exposed to OPs at either residential or workplace addresses varied by PON1 genotype; for exposed carriers of the "faster" metabolizer genotypes, ML or LL, we estimated lower odds ratios (range, 1.20-1.39) than for exposed carriers of the "slower" metabolizer genotype MM (range, 1.78-2.45) relative to unexposed carriers of the faster genotypes. We observed similarly increased ORs for exposure across PON1Q192R genotypes, but no differences across PON1C-108T genotypes. The largest ORs were estimated for exposed carriers of both PON1192QQ and PON155MM (OR range, 2.84-3.57). Several functional PON1 variants may act together to modify PD risk for ambient OP exposures. While either PON1L55M or PON1Q192R may be sufficient to identify increased susceptibility, carriers of both slow metabolizer variants seem most susceptible to OP exposures. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model.

    Science.gov (United States)

    Kim, Mi Jin; Park, Meeyoung; Kim, Dae Won; Shin, Min Jea; Son, Ora; Jo, Hyo Sang; Yeo, Hyeon Ji; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Kim, Duk-Soo; Kwon, Oh-Shin; Kim, Joon; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2015-09-01

    Parkinson's disease (PD) is an oxidative stress-mediated neurodegenerative disorder caused by selective dopaminergic neuronal death in the midbrain substantia nigra. Paraoxonase 1 (PON1) is a potent inhibitor of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) against oxidation by destroying biologically active phospholipids with potential protective effects against oxidative stress-induced inflammatory disorders. In a previous study, we constructed protein transduction domain (PTD) fusion PEP-1-PON1 protein to transduce PON1 into cells and tissue. In this study, we examined the role of transduced PEP-1-PON1 protein in repressing oxidative stress-mediated inflammatory response in microglial BV2 cells after exposure to lipopolysaccharide (LPS). Moreover, we identified the functions of transduced PEP-1-PON1 proteins which include, mitigating mitochondrial damage, decreasing reactive oxidative species (ROS) production, matrix metalloproteinase-9 (MMP-9) expression and protecting against 1-methyl-4-phenylpyridinium (MPP(+))-induced neurotoxicity in SH-SY5Y cells. Furthermore, transduced PEP-1-PON1 protein reduced MMP-9 expression and protected against dopaminergic neuronal cell death in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model. Taken together, these results suggest a promising therapeutic application of PEP-1-PON1 proteins against PD and other inflammation and oxidative stress-related neuronal diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. 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.

  7. Decreased paraoxonase1 activity and increased malondialdehyde and oxidative DNA damage levels in primary open angle glaucoma

    Science.gov (United States)

    Mumcu, Ugur Yilmaz; Kocer, Ibrahim; Ates, Orhan; Alp, H. Hakan

    2016-01-01

    To investigate the malondialdehyde (MDA) levels, paraoxonase1 (PON1) activity and 8-hydroxy 2-deoxyguanosine (8-OHdG) levels in the primary open angle glaucoma (POAG) patient. Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHdG by HPLC (high-performance liquid chromatography) and PON1 by spectrophotometry. The data obtained were analyzed statistically. MDA levels were 10.46±8.4 and 4.70±1.79 µmol; PON1 levels were 121±39.55 and 161.62±60.22 U/mL; and 8-OHdG values were 1.32±0.53/106 dG and 0.47±0.27/106 dG in the POAG patients and the control group, respectively. The difference was significant in MDA levels, 8-OHdG levels and PON1 activity in POAG patients in comparison with controls (P<0.001). We concluded that the observed increase in MDA and 8-OHdG levels may be correlated with decreased PON1 activity. Oxidative stress plays an important role in glaucoma development. PMID:27803873

  8. 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

  9. 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 measure...

  10. Paraoxonases: ancient substrate hunters and their evolving role in ischemic heart disease.

    Science.gov (United States)

    Martinelli, Nicola; Consoli, Letizia; Girelli, Domenico; Grison, Elisa; Corrocher, Roberto; Olivieri, Oliviero

    2013-01-01

    Interest in the role of paraoxonases (PON) in cardiovascular research has increased substantially over the past two decades. These multifaceted and pleiotropic enzymes are encoded by three highly conserved genes (PON1, PON2, and PON3) located on chromosome 7q21.3-22.1. Phylogenetic analysis suggests that PON2 is the ancient gene from which PON1 and PON3 arose via gene duplication. Although PON are primarily lactonases with overlapping, but distinct specificities, their physiologic substrates remain poorly characterized. The most interesting characteristic of PON, however, is their multifunctional roles in various biochemical pathways. These include protection against oxidative damage and lipid peroxidation, contribution to innate immunity, detoxification of reactive molecules, bioactivation of drugs, modulation of endoplasmic reticulum stress, and regulation of cell proliferation/apoptosis. In general, PON appear as "hunters" of old and new substrates often involved in athero- and thrombogenesis. Although reduced PON activity appears associated with increased cardiovascular risk, the correlation between PON genotype and ischemic heart disease remains controversial. In this review, we examine the biochemical pathways impacted by these unique enzymes and investigate the potential use of PON as diagnostic tools and their impact on development of future therapeutic strategies.

  11. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Aerobic training modulates the effects of exercise-induced oxidative stress on PON1 activity: a preliminary study.

    Science.gov (United States)

    Otocka-Kmiecik, Aneta; Lewandowski, Marek; Szkudlarek, Urszula; Nowak, Dariusz; Orlowska-Majdak, Monika

    2014-01-01

    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.

  14. Indices of Paraoxonase and Oxidative Status Do Not Enhance the Prediction of Subclinical Cardiovascular Disease in Mixed-Ancestry South Africans

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    M. Macharia

    2014-01-01

    Full Text Available We evaluated the association of indices of paraoxonase (PON1 and oxidative status with subclinical cardiovascular disease (CVD in mixed-ancestry South Africans. Participants were 491 adults (126 men who were stratified by diabetes status and body mass index (BMI. Carotid intima-media thickness (CIMT was used as a measure of subclinical CVD. Indices of PON1 and oxidative status were determined by measuring levels and activities (paraoxonase and arylesterase of PON1, antioxidant activity (ferric reducing antioxidant power and trolox equivalent antioxidant capacity, and lipid peroxidation markers (malondialdehyde and oxidized LDL. Diabetic subjects (28.9% displayed a significant decrease in PON1 status and antioxidant activity as well as increase in oxidized LDL and malondialdehyde. A similar profile was apparent across increasing BMI categories. CIMT was higher in diabetic than nondiabetic subjects (P<0.0001  but showed no variation across BMI categories. Overall, CIMT correlated negatively with indices of antioxidant activity and positively with measures of lipid oxidation. Sex, age, BMI, and diabetes altogether explained 29.2% of CIMT, with no further improvement from adding PON1 and/or antioxidant status indices. Though indices of PON1 and oxidative status correlate with CIMT, their measurements may not be useful for identifying subjects at high CVD risk in this population.

  15. Paraoxonase 1 polymorphisms and haplotypes and the risk for having offspring affected with spina bifida in Southeast Mexico.

    Science.gov (United States)

    Gonzalez-Herrera, Lizbeth; Martín Cerda-Flores, Ricardo; Luna-Rivero, Marianne; Canto-Herrera, Jorge; Pinto-Escalante, Doris; Perez-Herrera, Norma; Quintanilla-Vega, Betzabet

    2010-11-01

    Spina bifida (SB) is a common congenital malformation in Southeast Mexico. Parents of children with SB reside in areas with frequent pesticide spraying or have agriculture activities, suggesting potential exposure to pesticides. Paraoxonase 1 (PON1) is the responsible enzyme for deactivation of organophosphates (OP) in the central nervous system. Polymorphisms of PON1 genes influence the catalytic activity and plasma protein level of the enzyme, therefore, genotypic characterization of PON1 gene represents a potential predictor for susceptibility to OP-related effects. The frequency of PON1 haplotypes and polymorphisms (-108CT, L55M, and Q192R) were determined in this study. A case-control study was performed to evaluate the risk for having offspring affected by SB in 152 cases and 160 control parents. Polymorphisms were determined by PCR amplification and restriction fragment length polymorphism and Real Time-PCR. Odds ratios and confidence interval 95% were estimated. Genotype frequencies for the three PON1 polymorphisms were distributed according to Hardy-Weinberg expectations (p > 0.05) and were significantly different between cases and controls (p Mexico. © 2010 Wiley-Liss, Inc.

  16. To Study the Activity of Paraoxonase-1 and High Density Lipoprotein-Cholesterol in Alcoholic Liver Cirrhosis

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    Pooja Nemagoudar

    2017-01-01

    Full Text Available Background: Alcoholic liver cirrhosis is the most common complication of ethanol abuse. Alcoholic fatty liver progresses to alcoholic hepatitis, cirrhosis and liver failure. Lipoproteins are synthesized by the liver and secreted into the circulation. Alcoholic liver cirrhosis causes alteration in lipoprotein metabolism producing liver steatosis and necrosis. Paraoxonase-1 (PON-1 is an enzyme synthesized in liver and has an esterase activity towards lipid peroxides and circulates in plasma bound to High-Density Lipoproteins-cholesterol (HDL-c. Aim and Objectives: To determine the activity of PON-1 and levels of HDL-c in alcoholic liver disease and to correlate PON-1 activity with HDL-c. Materials and Methods: A Cross sectional study done in Department of Biochemistry and Department of Medicine, Belagavi Institute of Medical Sciences, Belagavi, Karnataka, India, from 1st December 2014 to 31st January 2016 Study included 50 males (age range 25-55 years with alcoholic liver cirrhosis and 50 healthy male participants (age range 25-55 years. PON-1 activity was estimated using spectrophotometric method by the hydrolysis of phenylacetate. HDL-c level was measured by cholesterol oxidase-peroxidase method. Results: The serum PON-1 activity and levels of HDL-c in patients with alcoholic liver cirrhosis were significantly reduced (p<0.001 compared with controls. Conclusion: A significant decrease in PON-1 and HDL-c in alcoholic liver cirrhosis may contribute to the risk of atherosclerosis in alcoholic liver cirrhosis patients.

  17. Association of paraoxonase-1 gene polymorphisms with insulin resistance in South Indian population.

    Science.gov (United States)

    Gomathi, Panneerselvam; Iyer, Anandi Chandramouli; Murugan, Ponniah Senthil; Sasikumar, Sundaresan; Raj, Nancy Bright Arul Joseph; Ganesan, Divya; Nallaperumal, Sivagnanam; Murugan, Maruthamuthu; Selvam, Govindan Sadasivam

    2018-04-15

    Insulin resistance plays a crucial role in the pathogenesis of type 2 diabetes and cardiovascular diseases. Recently, paraoxonase-1(PON1) is reported to have an ability to reduce insulin resistance by promoting glucose transporter-4 (GLUT-4) expression in vitro. Single nucleotide polymorphism (SNP) in PON1 is associated with variability in enzyme activity and concentration. Based on this we aimed to investigate the association of PON1 (Q192R and L55M) polymorphisms with the risk of developing insulin resistance in adult South Indian population. Two hundred and eighty seven (287) Type 2 diabetes patients and 293 healthy controls were enrolled in this study. All the study subjects were genotyped for PON1 (Q192R and L55M) missense polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) method. Fasting serum insulin level was measured by ELISA. The distribution of QR/RR and LM/MM genotypes were significantly higher in type 2 diabetes patients compared with healthy controls. Moreover, the R and M alleles were significantly associated with type 2 diabetes with an Odds Ratio of 1.68 (P  R genotypes were found to be significantly associated with higher BMI, cholesterol, triglycerides, LDL, fasting serum insulin and HOMA-IR. Further, the mutant allele or genotypes of PON1 L55M were associated with higher BMI, triglycerides, VLDL, fasting serum insulin and HOMA-IR among adult type 2 diabetes patients. PON1 (Q192R and L55M) polymorphisms may play a crucial role in pathogenesis and susceptibility of insulin resistance thus leads to the development of type 2 diabetes in South Indian population. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Synergistic effect of polymorphisms of paraoxonase gene cluster and arsenic exposure on electrocardiogram abnormality

    International Nuclear Information System (INIS)

    Liao, Y.-T.; Li, W.-F.; Chen, C.-J.; Prineas, Ronald J.; Chen, Wei J.; Zhang Zhuming; Sun, C.-W.; Wang, S.-L.

    2009-01-01

    Arsenic has been linked to increased prevalence of cancer and cardiovascular disease (CVD), but the long-term impact of arsenic exposure remains unclear. Human paraoxonase (PON1) is a high-density lipoprotein-associated antioxidant enzyme which hydrolyzes oxidized lipids and is thought to be protective against atherosclerosis, but evidence remains limited to case-control studies. Only recently have genes encoding enzymes responsible for arsenic metabolism, such as AS3MT and GSTO, been cloned and characterized. This study was designed to evaluate the synergistic interaction of genetic factors and arsenic exposure on electrocardiogram abnormality. A total of 216 residents from three tap water implemented villages of previous arseniasis-hyperendemic regions in Taiwan were prospectively followed for an average of 8 years. For each resident, a 12-lead conventional electrocardiogram (ECG) was recorded and coded by Minnesota Code standard criteria. Eight functional polymorphisms of PON1, PON2, AS3MT, GSTO1, and GSTO2 were examined for genetic susceptibility to ECG abnormality. Among 42 incident cases with ECG deterioration identified among 121 baseline-normal subjects, arsenic exposure was significantly correlated with incidence of ECG abnormality. In addition, polymorphisms in two paraoxonase genes were also found associated with the incidence of ECG abnormality. A haplotype R-C-S constituted by polymorphisms of PON1 Q192R, -108C/T and PON2 C311S was linked to the increased risk. Subjects exposed to high levels of As (cumulative As exposure > 14.7 ppm-year or drinking artesian well water > 21 years) and carrying the R-C-S haplotype had significantly increased risks for ECG abnormality over those with only one risk factor. Results of this study showed a long-term arsenic effect on ECG abnormality and significant gene-gene and gene-environment interactions linked to the incidence of CVD. This finding might have important implications for a novel and potentially useful

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

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    Luigi Mandrich

    Full Text Available 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.

  20. Paraoxonase 2 prevents the development of heart failure.

    Science.gov (United States)

    Li, Wei; Kennedy, David; Shao, Zhili; Wang, Xi; Kamdar, Andre Klaassen; Weber, Malory; Mislick, Kayla; Kiefer, Kathryn; Morales, Rommel; Agatisa-Boyle, Brendan; Shih, Diana M; Reddy, Srinivasa T; Moravec, Christine S; Tang, W H Wilson

    2018-05-02

    Mitochondrial oxidation is a major source of reactive oxygen species (ROS) and mitochondrial dysfunction plays a central role in development of heart failure (HF). Paraoxonase 2 deficient (PON2-def) mitochondria are impaired in function. In this study, we tested whether PON2-def aggravates HF progression. Using qPCR, immunoblotting and lactonase activity assay, we demonstrate that PON2 activity was significantly decreased in failing hearts despite increased PON2 expression. To determine the cardiac-specific function of PON2, we performed heart transplantations in which PON2-def and wild type (WT) donor hearts were implanted into WT recipient mice. Beating scores of the donor hearts, assessed at 4 weeks post-transplantation, were significantly decreased in PON2-def hearts when compared to WT donor hearts. By using a transverse aortic constriction (TAC) model, we found PON2 deficiency significantly exacerbated left ventricular remodeling and cardiac fibrosis post-TAC. We further demonstrated PON2 deficiency significantly enhanced ROS generation in heart tissues post-TAC. ROS generation was measured through dihydroethidium (DHE) using high-pressure liquid chromatography (HPLC) with a fluorescent detector. By using neonatal cardiomyocytes treated with CoCl 2 to mimic hypoxia, we found PON2 deficiency dramatically increased ROS generation in the cardiomyocytes upon CoCl 2 treatment. In response to a short CoCl 2 exposure, cell viability and succinate dehydrogenase (SDH) activity assessed by MTT assay were significantly diminished in PON2-def cardiomyocytes compared to those in WT cardiomyocytes. PON2-def cardiomyocytes also had lower baseline SDH activity. By using adult mouse cardiomyocytes and mitochondrial ToxGlo assay, we found impaired cellular ATP generation in PON2-def cells compared to that in WT cells, suggesting that PON2 is necessary for proper mitochondrial function. Our study suggests a cardioprotective role for PON2 in both experimental and human heart

  1. Effects of soy bean on serum paraoxonase 1 activity and lipoproteins in hyperlipidemic postmenopausal women.

    Science.gov (United States)

    Shidfar, Farzad; Ehramphosh, Elham; Heydari, Iraj; Haghighi, Ladan; Hosseini, Sharieh; Shidfar, Shahrzad

    2009-05-01

    Because of an unfavorable serum lipoprotein profile, postmenopausal women are at risk of cardiovascular disease. Soy protein may help protect against these risk factors, although its effect on paraoxonase 1 (PON1) is not clear. The aim of the present study was to determine the effects of soy protein on serum concentration of lipoproteins and PON1 activity in hypercholesterolemic postmenopausal women. In a double-blind randomized clinical trial with a parallel design, 52 hypercholesterolemic postmenopausal women were randomly assigned to 50 g/day soy protein containing 164 mg isoflavones or placebo, for 10 weeks. Serum lipoproteins and PON1 activity were measured at baseline and at the 10th week. There was significant increase in PON1 activity (P=0.029) and a significant decrease in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), LDL-C/high-density lipoprotein cholesterol (HDL-C), triacylglycerol/HDL-C and TC/HDL-C in the soy group compared with the placebo group (P=0.001, P=0.008, P=0.012, P=0.04 and P=0.029, respectively) at the end of the study. Similarly, PON1 activity was significantly increased (P=0.015) and LDL-C, TC, LDL-C/HDL-C, triacylglycerol/HDL-C and TC/HDL-C were significantly decreased (P=0.001, P=0.002, P=0.001, P=0.016 and P=0.001) at the end of the study compared with the beginning value in soy group. Soy protein reduces the cardiovascular disease risk in postmenopausal women because of both modest reductions in serum lipoproteins and an increase in PON1 activity.

  2. 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

    2017-12-01

    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.

  3. Paraoxonase polymorphisms PON1 192 and 55 and longevity in Italian centenarians and Irish nonagenarians. A pooled analysis.

    Science.gov (United States)

    Rea, Irene M; McKeown, Pascal P; McMaster, Dorothy; Young, Ian S; Patterson, Chris; Savage, Maurice J; Belton, Christine; Marchegiani, Francesca; Olivieri, Fabiola; Bonafe, Massimiliano; Franceschi, Claudio

    2004-04-01

    PON1, an arylesterase, associated with high density lipoprotein (HDL), protects low density lipoprotein (LDL) against oxidative modification. Common polymorphisms PON1 55 (L/M) and 192 (Q/R) in the PON1 gene associate with atherosclerosis and heart disease. Because long-lived people seem protected from premature vascular death, we conducted a pooled statistical analysis to assess any association between these polymorphisms and longevity in a large combined group of Italian centenarians and octo/nonagenarians from Northern Ireland (NI). Separated DNA was available from 1479 subjects from Italy and Northern Ireland (NI). In Italy 308 centenarians (males 67, females 241, mean age 100.8, SD2.1 years) and 579 young controls (males 347, females 232, mean age 40.7, SD 12.7 years) were included in the study. In NI, 296 octo/nonagenarians (males 92, females 204, mean age 89.8, SD 5.7 years) and 296 young sex-matched subjects (mean age 13.0, SD 1.4 years) had available DNA. PON1 55 (L/M) and 192 (Q/R) polymorphisms were studied using a PCR-RFLP approach. There was a significant difference in PON1 192 genotypes in Italian centenarians compared to younger controls (X(2)= 6.8, df = 2 p= 0.03) and a similar but non significant trend between octo/nonagenarian and young subjects in NI (X(2) = 4.0, df=2, p=0.14). Using logistic regression analysis on the combined Italian and Irish datasets, there was a small survival advantage for centenarian and octo/nonagenarian subjects who were heterozygous for PON1 192 R allele, (OR 1.3, CI 1-1.6; p=0.04 with a stepwise increase for RR homozygous subjects (OR 1.7, CI 1.1-2.6; p = 0.02) compared to QQ subjects. Comparing R and Q alleles there was a survival advantage for octo/nonagenarian/centenarian subjects who carried the R allele (OR 1.3, CI 1.1-1.5; p = 0.007) but there was no sex-specific effect p =0.77) LL, LM and MM genotypes of PON 55 polymorphisms showed similar frequencies in Italy (39.9, 47.0, 13.1%) and Ireland (39.5, 48.6, 11

  4. 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.

  5. 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.

  6. 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

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

    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...... was observed in prenatally pesticide exposed children carrying the PON1 192R-allele. Differentially methylated genes were enriched in several neuroendocrine signaling pathways including dopamine-DARPP32 feedback (appetite, reward pathways), corticotrophin releasing hormone signaling, nNOS, neuregulin signaling...

  8. Serum Paraoxonase-1 Concentration as a Potential Predictor of Urinary Bladder Cancer Recurrence. A Five Year Follow-Up Study.

    Science.gov (United States)

    Iftimie, Simona; García-Heredia, Anabel; Pujol-Bosch, Francesc; Pont-Salvadó, Antoni; López-Azcona, Ana Felisa; Hernández-Aguilera, Anna; Cabré, Noemí; Luciano-Mateo, Fedra; Fort-Gallifa, Isabel; Castro, Antoni; Camps, Jordi; Joven, Jorge

    2018-04-23

    This study provides preliminary information on the usefulness of measuring serum paraoxonase-1 (PON1) concentration and activity (and other inflammatory markers) to predict tumor recurrence in patients with urinary bladder cancer. We studied a total of 39 hospitalized patients in whom the diagnosis of urinary bladder cancer was confirmed by transurethral resection. After five years of follow-up, 29 patients presented with tumor recurrence. As control subjects, we also studied 61 healthy subjects and a further 132 hospitalized patients who had a urinary catheter-related infection due to causes other than cancer. Results showed that urinary bladder patients had lower serum PON1 concentration and activity, and higher chemokine (C-C motif) ligand 2, C-reactive protein, and procalcitonin concentrations than the control individuals. Patients with tumor recurrence had significantly lower serum PON1 concentration than patients without tumor recurrence. The mean area under the curve of the receiver operating characteristics plot for serum PON1 concentration in discriminating patients with and those without tumor recurrence was 0.755 and the best combination of sensitivity and specificity was obtained at PON1 = 100 mg/L (0.72 and 0.80, respectively). Establishing this value as a cut-off, positive predictive value was = 0.91, and negative predictive value was = 0.50. These results suggest that the measurement of serum PON1 concentration may be a high-sensitivity marker of tumor recurrence in urinary bladder cancer patients. Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.

  9. The influence of gemfibrozil on malondialdehyde level and paraoxonase 1 activity in wistar and fisher rats.

    Science.gov (United States)

    Macan, Marija; Marija, Macan; Konjevoda, Paško; Paško, Konjevoda; Lovric, Jasna; Jasna, Lovrić; Koprivanac, Marijan; Marijan, Koprivanac; Kelava, Marta; Marta, Kelava; Vrkic, Nada; Nada, Vrkić; Bradamante, Vlasta; Vlasta, Bradamante

    2011-06-01

    There are diverse experimental data about the influence of gemfibrozil (GEM) on the production of hydrogen peroxide (H(2)O(2)) and antioxidant enzymes. We investigated the influence of GEM treatment on the production of malondialdehyde (MDA) level in tissues of normolipidaemic Wistar and Fisher rats which is an index of lipid peroxidation. Because serum paraoxonase 1 (PON1) is an important enzyme with specific protective function on metabolism of lipid peroxides, we examined the influence of GEM on PON1 activity in liver and serum. MDA level and enzyme activities were also determined 10 days after withdrawal of GEM treatment. The significantly increased levels of MDA in liver, kidney and heart of both rat strains were obtained after 3 weeks of GEM treatment. We propose two possibilities for the increase of MDA levels caused by GEM, induction of peroxisome proliferation and activities of enzymes that participated in occurrence of H(2)O(2) and possible reduction of enzyme activities including in H(2)O(2) metabolism. Ten days after withdrawal of GEM treatment, MDA levels in all tissue levels of both rat strains were less in comparison with GEM treatment. GEM caused a significant drop of PON1 activity in serum and liver of Fisher rats, and in liver of Wistar rats. We suggest that GEM, through induction of lipid peroxidation, caused the damage of hepatocytes with consequent reduction of PON1 synthesis. The increase in PON1 activity in serum and tissues of both rat strains 10 days after withdrawal of GEM treatment shows the fast recovery of enzyme synthesis. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

  10. Vasospastic angina and microvascular angina are differentially influenced by PON1 A632G polymorphism in the Japanese.

    Science.gov (United States)

    Mashiba, Junko; Koike, George; Kamiunten, Hitoshi; Ikeda, Manami; Sunagawa, Kenji

    2005-12-01

    Ethnicity and smoking are well-known risk factors for the pathogenesis of coronary vasospasm. Oxidative stress induced by smoking plays a crucial role in coronary vasospasm, but is not enough to account for the pathogenesis of coronary vasospasm, indicating that genetic factors are strongly involved. The study group comprised 162 vasospastic angina patients (VSAs), 61 microvascular angina patients (MVAs) and 61 non-responders (NRs) diagnosed by acetylcholine provocation test. Four polymorphisms of the oxidative stress related genes, cytochrome b-245, alpha polypeptide gene (CYBA) C242T and A640G, paraoxonase 1 gene (PON1) A632G, phospholipase A2 group VII gene (PLA2G7) G994T were genotyped. Allele frequency of PON1 632-G was significantly higher in both the VSA with dominant fashion and the MVA with recessive fashion compared with NR. This association was strongly influenced by gender in the MVA only. There were no significant associations between the other polymorphisms and coronary vasospasm. In addition, the allele frequency of PON1 632-G in the Japanese was higher than in Caucasians. There was a significant association between PON1 A632G polymorphism and MVA as well as VSA, but the impact of this on VSA and MVA is different in the Japanese.

  11. 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.

  12. Daily supplementation with fresh pomegranate juice increases paraoxonase 1 expression and activity in mice fed a high-fat diet.

    Science.gov (United States)

    Estrada-Luna, D; Martínez-Hinojosa, E; Cancino-Diaz, J C; Belefant-Miller, H; López-Rodríguez, G; Betanzos-Cabrera, G

    2018-02-01

    Studies have found that pomegranate juice (PJ) consumption increases the binding of high-density lipoproteins (HDL) to paraoxonase 1 (PON1), thus increasing the catalytic activity of this enzyme. PON1 is an antioxidant arylesterase synthesized in the liver and transported in plasma in association with HDL. Decreased levels of PON1 are associated with higher levels of cholesterol. We determined the effects of PJ on body weight, cholesterol, and triacylglycerols through 5 months of supplementation. In addition, the effect of PJ on pon1 gene expression in the liver was also measured by RT-qPCR as well as the activity in serum by a semiautomated method using paraoxon as a substrate. CD-1 mice were either fed a control diet or were fed a high-fat diet 1.25% (wt/wt) cholesterol, 0.5% (wt/wt) sodium cholate, and 15% (wt/wt) saturated fat. 300 μL of PJ containing 0.35 mmol total polyphenols was administered by oral gavage to half of the high fat mice daily. The rest of the high fat mice and the control mice were administered with 300 μL of water. PJ-supplemented animals had significantly higher levels of expression of pon1 compared to the unsupplemented group. PJ-supplemented animals had twice the PON1 activity of the unsupplemented group. In addition, PJ-supplemented animals had the lowest body weight and significantly reduced cholesterol and triacylglycerol levels, although the tricylglycerol levels were not consistently decreased. These results suggest that PJ protects against the effects of a high-fat diet in body weight, and cholesterol levels.

  13. Impact of the 24-h ultramarathon race on homocysteine, oxidized low-density lipoprotein, and paraoxonase 1 levels in professional runners.

    Science.gov (United States)

    Benedetti, Serena; Catalani, Simona; Peda, Federica; Luchetti, Francesca; Citarella, Roberto; Battistelli, Serafina

    2018-01-01

    The impact of the 24-h ultramarathon race on homocysteine (Hcy) and oxidized low-density lipoprotein (oxLDL) levels, two well-recognized cardiovascular risk factors, has not been deeply investigated. Similarly, no information exists on paraoxonase 1 (PON1), an antioxidant enzyme associated with high-density lipoproteins, which may detoxify oxLDL and Hcy-thiolactone, hence preventing their proatherogenic action. Taking this into account, a competitive 24-h ultramarathon race was organized in Reggio-Emilia (Italy) recruiting professional runners (n = 14) from the Italian Ultramarathon and Trail Association. Blood samples were collected from each participant before, during (14 h), and immediately after (24 h) the competition, thus to monitor the serum changes in Hcy, oxLDL, and PON1 levels, as well as other oxidative stress-related parameters, namely reactive oxygen metabolites (ROM) and total antioxidant capacity (PAT). As a result, a significant PON1 increase was recorded after 14 h of racing that persisted until the end of the performance. The same trend was observed for PAT values, which positively correlated to PON1 levels (R = 0.643, P<0.001). Hcy, oxLDL, and ROM remained almost unchanged throughout the competition. In conclusion, the present study suggested a protective role of PON1 in sustaining the antioxidant defense system and contrasting lipoprotein oxidative modifications over the 24-h race, and did not specifically evidence either Hcy or oxLDL accumulation in such challenging sporting events.

  14. 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

  15. Association of lead, cadmium and mercury with paraoxonase 1 activity and malondialdehyde in a general population in Southern Brazil.

    Science.gov (United States)

    Almeida Lopes, Ana Carolina Bertinde; Urbano, Mariana Ragassi; Souza-Nogueira, André de; Oliveira-Paula, Gustavo H; Michelin, Ana Paula; Carvalho, Maria de Fátima H; Camargo, Alissana Ester Iakmiu; Peixe, Tiago Severo; Cabrera, Marcos Aparecido Sarria; Paoliello, Monica Maria Bastos

    2017-07-01

    Metal exposure is associated with increased oxidative stress (OS), which is considered an underlying mechanism of metal-induced toxicity. Malondialdehyde (MDA) is a final product of lipid peroxidation, and it has been extensively used to evaluate metal-induced OS. Pro-oxidant effects produced by metals can be mitigated by paraoxonase 1 (PON1), an antioxidant enzyme known to prevent cardiovascular disease and atherosclerosis. Among other factors, the Q192R polymorphism and the exposure to heavy metals have been known to alter PON1 activity. Here, we evaluated the association of blood lead (Pb), cadmium (Cd) and mercury (Hg) levels with PON1 activity, and with MDA concentrations in a randomly selected sample of Brazilian adults aged 40 years or older, living in an urban area in Southern Brazil. A total of 889 subjects were evaluated for blood Pb and Cd levels, and 832 were tested for Hg. Geometric mean of blood Pb, Cd and Hg was 1.93μg/dL, 0.06μg/L and 1.40μg/L, respectively. PON1 activity was significantly different among various genotypes: QQ (PON1=121.4U/mL), QR (PON1=87.5U/mL), and RR (PON1=55.2U/mL), p<0.001. PON1 genotypes were associated only with Cd blood levels. Those with QR genotype had Cd concentrations higher (0.07μg/L) than those with the RR genotype (0.04μg/L) with p=0.034. However, PON1 activity was not significantly associated with metal concentrations. Cluster analysis showed that men who reported to be current smokers and drinkers with higher blood Pb and Cd levels, had significantly lower PON1 activity than non-smokers or -drinkers, and women with lower Pb and Cd levels. RR genotype carriers had lower PON1 activity than those with the QR genotype, and had higher levels of Pb and Cd compared with other genotype carriers. For blood Hg, no association with PON1 activity or genotype was noted. We found low levels of Pb, Cd and Hg in environmentally exposed Brazilian adults. Cd concentrations were increased in subjects with QR genotype. Those with

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Association of Paraoxonase-1 Q192R (rs662 Single Nucleotide Variation with Cardiovascular Risk in Coffee Harvesters of Central Colombia

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    Fernando Siller-López

    2017-01-01

    Full Text Available Paraoxonase 1 (PON1, a high-density lipoprotein-associated antioxidant enzyme, hydrolyzes several organophosphate pesticides and oxidized lipids. The PON1 Q192R polymorphism affects the catalytic efficiency and is considered a risk factor for pesticide intoxication and cardiovascular disease (CVD but the association is not consistent between individuals or populations. We aimed to study the association of PON1 Q192R polymorphism with CVD risk in coffee harvesters of central Colombia. Demographics were collected from 205 subjects via standardized questionnaires. Lipid profiles and serum butyrylcholinesterase (BChE were measured by standard procedures. The calculated 10-year atherosclerotic CVD (ASCVD risk was used as the cardiovascular risk estimate. Q192R genotype was determined by real-time PCR. Prevalence of hypertension, hypercholesterolemia, and the 10-year ASCVD risk was 33%, 62%, and 22%, respectively. BChE levels were no indicative of recent pesticide exposure, although a positive correlation was observed with BChE and hypercholesterolemia. The Q192R genotype frequencies were 38% (QQ, 44% (QR, and 18% (RR. We found an association of the 192Q genotype with hypertension. The results of this study signal the importance to evaluate the influence and potential interactions of BChE and PON1 192Q allele with known genetic and environmental factors implicated in the pathogenesis of CVD.

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

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    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

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

    International Nuclear Information System (INIS)

    Moreno-Banda, G.; Blanco-Munoz, J.; Lacasana, M.; Rothenberg, S.J.; Aguilar-Garduno, C.; Gamboa, R.; Perez-Mendez, O.

    2009-01-01

    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

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

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    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.

  1. Relationship of serum resistin level to traits of metabolic syndrome and serum paraoxonase 1 activity in a population with a broad range of body mass index.

    Science.gov (United States)

    Bajnok, L; Seres, I; Varga, Z; Jeges, S; Peti, A; Karanyi, Z; Juhasz, A; Csongradi, E; Mezosi, E; Nagy, E V; Paragh, G

    2008-11-01

    The relationship between resistin, one of the adipokines, and metabolic syndrome is not fully elucidated. Altered activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) that participates in the antioxidant defense mechanisms of HDL may have an important role in the obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum levels of leptin have been demonstrated. Our aim was to investigate the association of serum levels of resistin with (i) PON1 activity, and (ii) parameters of metabolic syndrome, including some that are additional for research. A total of 74 Caucasian subjects were recruited into the study and divided into 3 age and sex-matched groups. Group 1, 25 non-diabetic overweight/obese subjects with BMI of 28-39.9 kg/m (2); group 2, 25 non-diabetic obese patients with BMI >or=40 kg/m (2); and the control group 3, 24 healthy, normal-weight control subjects. Serum levels of resistin were correlated negatively with BMI (r=-0.27, Pcorrelated positively with PON1 (r=0.24, PHDL-C. During multiple regression analyses BMI and TBARS were independent predictors of PON1, while age, gender, blood pressure, HOMA-IR, LDL-C, HDL-C, and resistin were not. Among the study subjects, serum levels of resistin showed a positive, although not independent correlation with serum PON1, and a negative correlation with numerous parameters of the metabolic syndrome (i.e. adiposity, blood pressure, levels of leptin, free fatty acid, glycosylated hemoglobin, and lipid peroxidation). BMI and TBARS are independent predictors of PON1 activity.

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

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    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

  3. Paraoxonase activity in patients with chronic renal failure and hepatic insufficiency

    International Nuclear Information System (INIS)

    Jamal, S.; Ishaq, M.; Hussain, S.M.W.; Alam, J.A.; Hussain, S.

    2010-01-01

    Paraoxonase (PON), a high density lipoprotein (HDL) associated enzyme, is believed to protect against the oxidation of low density lipoprotein (LDL) and hence affects the risk of vascular disease. PON is sensitive to oxidants and is inactivated by oxidized lipids, and thus it can be postulated that increased oxidative stress may decrease plasma PON activity in patients with chronic renal failure (CRF) and hepatic insufficiency (HI). Moreover, in CRF and HI patients, in contrast to normal individuals, higher levels of plasma biochemical parameters and liver enzymes had an inverse correlation with PON activity. In this study we aimed to investigate PON activity, total bilirubin, creatinine, urea and liver enzymes alanine aminotransferase and alkaline phosphatase that are the index of renal and hepatic insufficiency. We have analyzed plasma from pre-dialysis patients and compared the results with the normal individuals. We observed a positive association of PON activity with that of the disease state i.e. the activity of this enzyme was significantly lower in the patients (p < 0.001). Furthermore, the indicators of renal and hepatic insufficiency were significantly elevated as compared to the normal subjects. Based on our results we conclude that in CRF and HI, in contrast to normal individuals, higher levels of plasma biochemical parameters and liver enzymes had inverse correlation with PON activity. Collectively, these findings may add details to the understanding of the role that PON plays in chronic renal failure and hepatic insufficiency. (author)

  4. Homocysteine threshold value based on cystathionine beta synthase and paraoxonase 1 activities in mice.

    Science.gov (United States)

    Hamelet, J; Aït-Yahya-Graison, E; Matulewicz, E; Noll, C; Badel-Chagnon, A; Camproux, A-C; Demuth, K; Paul, J-L; Delabar, J M; Janel, N

    2007-12-01

    Hyperhomocysteinaemia is a metabolic disorder associated with the development of premature atherosclerosis. Among the determinants which predispose to premature thromboembolic and atherothrombotic events, serum activity of paraoxonase 1, mainly synthesized in the liver, has been shown to be a predictor of cardiovascular disease and to be negatively correlated with serum homocysteine levels in human. Even though treatments of hyperhomocysteinaemic patients ongoing cardiovascular complications are commonly used, it still remains unclear above which homocysteine level a preventive therapy should be started. In order to establish a threshold of plasma homocysteine concentration we have analyzed the hepatic cystathionine beta synthase and paraoxonase 1 activities in a moderate to intermediate murine model of hyperhomocysteinaemia. Using wild type and heterozygous cystathionine beta synthase deficient mice fed a methionine enriched diet or a control diet, we first studied the link between cystathionine beta synthase and paraoxonase 1 activities and plasma homocysteine concentration. Among the animals used in this study, we observed a negative correlation between plasma homocysteine level and cystathionine beta synthase activity (rho=-0.52, P=0.0008) or paraoxonase 1 activity (rho=-0.49, P=0.002). Starting from these results, a homocysteine cut-off value of 15 microm has been found for both cystathionine beta synthase (P=0.0003) and paraoxonase 1 (P=0.0007) activities. Our results suggest that both cystathionine beta synthase and paraoxonase 1 activities are significantly decreased in mice with a plasma homocysteine value greater than 15 microm. In an attempt to set up preventive treatment for cardiovascular disease our results indicate that treatments should be started from 15 microm of plasma homocysteine.

  5. Paraoxonase 1 (Q192R) gene polymorphism, coronary heart disease and the risk of a new acute coronary event.

    Science.gov (United States)

    Martínez-Quintana, Efrén; Rodríguez-González, Fayna; Medina-Gil, José María; Garay-Sánchez, Paloma; Tugores, Antonio

    Paraoxonase 1 (PON1) plays a major role in the oxidation of low density lipoprotein and in the prevention of coronary atherogenesis. In this context, coding region polymorphisms of PON1 gene, responsible for the enzyme activity, has become of interest as a marker for atherogenesis. A study and follow-up was conducted on 529 patients with an acute coronary event in order to assess the association between the PON1 Q192R (rs662;A/G) polymorphism, the type of acute coronary syndrome, cardiovascular risk factors (arterial hypertension, diabetes mellitus, dyslipidaemia, and smoking), the extent and severity of coronary atherosclerosis, and the medium-term clinical follow-up. The QQ genotype was found in 245 (46.3%) patients, with 218 (41.2%) patients showing the QR genotype, and 66 (14.5%) patients had the RR genotype. No significant differences were found between the QQ and QR/RR genotypes as regards the clinical characteristics, the analytical data, and the angiographic variables. Similarly, Kaplan-Meier survival analysis showed no significant differences in presenting with a new acute coronary event (p=0.598), cardiac mortality (p=0.701), stent thrombosis (p=0.508), or stent re-stenosis (p=0.598) between QQ and QR/RR genotypes during the follow-up period (3.3±2.2 years). In patients with an acute coronary syndrome, the PON1 Q192R genotypes did not influence the risk of suffering a new acute coronary event during the medium-term follow-up. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. PON1Q192R genetic polymorphism modifies organophosphorous pesticide effects on semen quality and DNA integrity in agricultural workers from southern Mexico

    International Nuclear Information System (INIS)

    Perez-Herrera, N.; Polanco-Minaya, H.; Salazar-Arredondo, E.; Solis-Heredia, M.J.; Hernandez-Ochoa, I.; Rojas-Garcia, E.; Alvarado-Mejia, J.; Borja-Aburto, V.H.; Quintanilla-Vega, B.

    2008-01-01

    Pesticide exposure, including organophosphorous (OP) insecticides, has been associated with poor semen quality, and paraoxonase (PON1), an enzyme involved in OP deactivation, may have a role on their susceptibility, due to PON1 polymorphisms. Our objective was to evaluate the role of PON1Q192R polymorphism on the susceptibility to OP toxicity on semen quality and DNA integrity in agricultural workers. A cross-sectional study was conducted in farmers with Mayan ascendancy from southeastern Mexico chronically exposed to pesticides; mostly OP. Fifty four agricultural workers (18-55 years old) were included, who provided semen and blood samples. Semen quality was evaluated according to WHO, sperm DNA damage by in situ-nick translation (NT-positive cells), PON1Q192R polymorphism by real-time PCR and serum PON1 activity by using phenylacetate and paraoxon. Two OP exposure indexes were created: at the month of sampling and during 3 months before sampling, representing the exposure to spermatids-spermatozoa and to cells at one spermatogenic cycle, respectively. PON1 192R and 192Q allele frequencies were 0.54 and 0.46, respectively. Significant associations were found between OP exposure at the month of sampling and NT-positive cells and sperm viability in homozygote 192RR subjects, and dose-effect relationships were observed between OP exposure during 3 months before sampling and sperm quality parameters and NT-positive cells in homozygote 192RR farmers. This suggests that cells at all stages of spermatogenesis are target of OP, and that there exists an interaction between OP exposure and PON1Q192R polymorphism on these effects; farmers featuring the 192RR genotype were more susceptible to develop reproductive toxic effects by OP exposure

  7. Associations of maternal organophosphate pesticide exposure and PON1 activity with birth outcomes in SAWASDEE birth cohort, Thailand

    Science.gov (United States)

    Naksen, Warangkana; Prapamontol, Tippawan; Mangklabruks, Ampica; Chantara, Somporn; Thavornyutikarn, Prasak; Srinual, Niphan; Panuwet, Parinya; Ryan, P. Barry; Riederer, Anne M.; Barr, Dana Boyd

    2015-01-01

    Prenatal organophosphate (OP) pesticide exposure has been reported to be associated with adverse birth outcomes and neurodevelopment. However, the mechanisms of toxicity of OP pesticides on human fetal development have not yet been elucidated. Our pilot study birth cohort, the Study of Asian Women and Offspring’s Development and Environmental Exposures (SAWASDEE cohort) aimed to evaluate environmental chemical exposures and their relation to birth outcomes and infant neurodevelopment in 52 pregnant farmworkers in Fang district, Chiang Mai province, Thailand. A large array of data was collected multiple times during pregnancy including approximately monthly urine samples for evaluation of pesticide exposure, three blood samples for pesticide-related enzyme measurements and questionnaire data. This study investigated the changes in maternal acetylcholinesterase (AChE) and paraoxonase 1 (PON1) activities and their relation to urinary diakylphosphates (DAPs), class-related metabolites of OP pesticides, during pregnancy. Maternal AChE, butyrylcholinesterase (BChE) and PON1 activities were measured three times during pregnancy and urinary DAP concentrations were measured, on average, 8 times from enrollment during pregnancy until delivery. Among the individuals in the group with low maternal PON1 activity (n = 23), newborn head circumference was negatively correlated with log10 maternal ΣDEAP and ΣDAP at enrollment (gestational age=12±3 weeks; β = −1.0 cm, p = 0.03 and β = −1.8 cm, p <0.01, respectively) and at 32 weeks pregnancy (β = −1.1 cm, p = 0.04 and β = −2.6 cm, p = 0.01, respectively). Furthermore, among these mothers, newborn birthweight was also negatively associated with log10 maternal ΣDEAP and ΣDAP at enrollment (β = −219.7 g, p = 0.05 and β = −371.3 g, p = 0.02, respectively). Associations between maternal DAP levels and newborn outcomes were not observed in the group of participants with high maternal PON1 activity. Our results

  8. The platelet activating factor acetyl hydrolase, oxidized low-density lipoprotein, paraoxonase 1 and arylesterase levels in treated and untreated patients with polycystic ovary syndrome.

    Science.gov (United States)

    Carlioglu, Ayse; Kaygusuz, Ikbal; Karakurt, Feridun; Gumus, Ilknur Inegol; Uysal, Aysel; Kasapoglu, Benan; Armutcu, Ferah; Uysal, Sema; Keskin, Esra Aktepe; Koca, Cemile

    2014-11-01

    To evaluate the platelet activating factor acetyl hydrolyze (PAF-AH), oxidized low-density lipoprotein (ox-LDL), paraoxonase 1 (PON1), arylesterase (ARE) levels and the effects of metformin and Diane-35 (ethinyl oestradiol + cyproterone acetate) therapies on these parameters and to determine the PON1 polymorphisms among PCOS patients. Ninety patients with PCOS, age 30, and body mass index-matched healthy controls were included in the study. Patients were divided into three groups: metformin treatment, Diane-35 treatment and no medication groups. The treatment with metformin or Diane-35 was continued for 6 months and all subjects were evaluated with clinical and biochemical parameters 6 months later. One-way Anova test, t test and non-parametric Mann-Whitney U tests were used for statistical analysis. PAF-AH and ox-LDL levels were statistically significantly higher in untreated PCOS patients than controls, and they were statistically significantly lower in patients treated with metformin or Diane-35 than untreated PCOS patients. In contrast, there were lower PON1 (not statistically significant) and ARE (statistically significant) levels in untreated PCOS patients than the control group and they significantly increased after metformin and Diane-35 treatments. In PCOS patients serum PON1 levels for QQ, QR and RR phenotypes were statistically significantly lower than the control group. In patients with PCOS, proatherogenic markers increase. The treatment of PCOS with metformin or Diane-35 had positive effects on lipid profile, increased PON1 level, which is a protector from atherosclerosis and decreased the proatherogenic PAF-AH and ox-LDL levels.

  9. Terminalia pallida fruit ethanolic extract ameliorates lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase in isoproterenol-induced myocardial infarcted rats

    Directory of Open Access Journals (Sweden)

    Althaf Hussain Shaik

    2018-03-01

    Full Text Available The present study aimed to evaluate the effect of Terminalia pallida fruit ethanolic extract (TpFE on lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase (PON in isoproterenol (ISO-induced myocardial infarcted rats. PON is an excellent serum antioxidant enzyme which involves in the protection of low density lipoprotein cholesterol (LDL-C from the process of oxidation for the prevention of cardiovascular diseases. ISO caused a significant increase in the concentration of total cholesterol, triglycerides, LDL-C, very low density lipoprotein cholesterol and lipid peroxidation whereas significant decrease in the concentration of high density lipoprotein cholesterol. ISO administration also significantly decreased the activities of lecithin cholesterol acyl transferase, PON and lipoprotein lipase whereas significantly increased the activity of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Oral pretreatment of TpFE at doses 100, 300 and 500 mg/kg body weight (bw and gallic acid (15 mg/kg bw for 30 days challenged with concurrent injection of ISO (85 mg/kg bw on 29th and 30th day significantly attenuated these alterations and restored the levels of lipids, lipoproteins and the activities of lipid metabolizing enzymes. Also TpFE significantly elevated the serum antioxidant enzyme PON. This is the first report revealed that pretreatment with TPFE ameliorated lipid metabolic marker enzymes and increased the antioxidant PON in ISO treated male albino Wistar rats. Keywords: Terminalia pallida fruit, Gallic acid, Isoproterenol, Lipid metabolism marker enzymes, Paraoxonase, Myocardial infarction

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

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    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.

  11. Low Levels of Serum Paraoxonase Activities are Characteristic of Metabolic Syndrome and May Influence the Metabolic-Syndrome-Related Risk of Coronary Artery Disease

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    Nicola Martinelli

    2012-01-01

    Full Text Available Low concentrations of plasma high-density lipoprotein (HDLs are characteristic in metabolic syndrome (MS. The antioxidant ability of HDLs is, at least in part, attributable to pleiotropic serum paraoxonase (PON1. Different PON1 activities have been assessed in 293 subjects with (=88 or without MS (=205 and with (=195 or without (=98 angiographically proven coronary artery disease (CAD. MS subjects had low PON1 activities, with a progressively decreasing trend by increasing the number of MS abnormalities. The activity versus 7-O-diethyl phosphoryl,3-cyano,4-methyl,7-hydroxycoumarin (DEPCyMC, which is considered a surrogate marker of PON1 concentration, showed the most significant association with MS, independently of both HDL and apolipoprotein A-I levels. Subjects with MS and low DEPCyMCase activity had the highest CAD risk (OR 4.34 with 95% CI 1.44–13.10, while no significant increase of risk was found among those with MS but high DEPCyMCase activity (OR 1.45 with 95% CI 0.47–4.46. Our results suggest that low PON1 concentrations are typical in MS and may modulate the MS-related risk of CAD.

  12. Low levels of serum paraoxonase activities are characteristic of metabolic syndrome and may influence the metabolic-syndrome-related risk of coronary artery disease.

    Science.gov (United States)

    Martinelli, Nicola; Micaglio, Roberta; Consoli, Letizia; Guarini, Patrizia; Grison, Elisa; Pizzolo, Francesca; Friso, Simonetta; Trabetti, Elisabetta; Pignatti, Pier Franco; Corrocher, Roberto; Olivieri, Oliviero; Girelli, Domenico

    2012-01-01

    Low concentrations of plasma high-density lipoprotein (HDLs) are characteristic in metabolic syndrome (MS). The antioxidant ability of HDLs is, at least in part, attributable to pleiotropic serum paraoxonase (PON1). Different PON1 activities have been assessed in 293 subjects with (n = 88) or without MS (n = 205) and with (n = 195) or without (n = 98) angiographically proven coronary artery disease (CAD). MS subjects had low PON1 activities, with a progressively decreasing trend by increasing the number of MS abnormalities. The activity versus 7-O-diethyl phosphoryl,3-cyano,4-methyl,7-hydroxycoumarin (DEPCyMC), which is considered a surrogate marker of PON1 concentration, showed the most significant association with MS, independently of both HDL and apolipoprotein A-I levels. Subjects with MS and low DEPCyMCase activity had the highest CAD risk (OR 4.34 with 95% CI 1.44-13.10), while no significant increase of risk was found among those with MS but high DEPCyMCase activity (OR 1.45 with 95% CI 0.47-4.46). Our results suggest that low PON1 concentrations are typical in MS and may modulate the MS-related risk of CAD.

  13. 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.

  14. 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.

  15. Human paraoxonase and HDL-cholesterol in pakistan patients with acute myocardial infarction and normal healthy adults

    International Nuclear Information System (INIS)

    Iqbal, I.P.; Khan, A.H.; Mehboobali, N.

    2007-01-01

    Human serum paraoxonase is a high density lipoprotein (HDL)-bound enzyme exhibiting antiatherogenic properties. The aim of this study was to investigate any relationship between serum paraoxonase activity and serum levels of HDL-cholesterol in Pakistani patients with acute myocardial infarction (AMI) compared to normal healthy subjects and to examine possible association between serum paraoxonase activity and AMI in Pakistani population. In a case-control study, serum paraoxonase activity and serum levels of HDL-cholesterol and LDL-cholesterol were monitored in 164 Pakistani patients with AMI and 106 normal healthy adults matched for gender, BMI and age within 10 years. Mean serum concentration of HDL-cholesterol and mean serum paraoxonase activity in AMI patients were not significantly different from the corresponding values in normal healthy subjects. Mean serum paraoxonase activity value was significantly lower in normal healthy subjects with low HDL-cholesterol (serum levels < 40mg/dl) compared to the value in those with normal levels of HDL-cholesterol (P=0.04). In AMI patients, paraoxonase activity was lower in subjects with low HDL-cholesterol compared to those with normal levels of HDL-cholesterol, however, the decrease was not statistically significant. Correlation analyses of the data revealed a moderate association of paraoxonase activity with HDL-cholesterol (Pearson's r= 0.225, P<0.01 for AMI patients and r=0.281, P<0.01 for normal healthy controls). Seventy three percent of normal healthy subjects and 65% of AMI patients in this study had low HDL-cholesterol. Low serum paraoxonase activity and high prevalence of low HDL-cholesterol in Pakistani population could be contributing to the high rates of coronary heart disease in this population. (author)

  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

    International Nuclear Information System (INIS)

    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

    2011-01-01

    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: ► Role of CYP1A1, CYP3A5, CYP2C, CYP2D6 and PON1 genotypes on DNA damage. ► Workers exposed to some OPs demonstrated increased DNA damage. ► CYP2D6 *3 PM and PON1 (Q192R and L55M) genotypes are associated with DNA damage. ► Concomitant presence of certain CYP2D6 and PON1 genotypes can increase DNA damage.

  17. Association between paraoxonase-1 gene Q192R and L55M polymorphisms in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) in a population from Cairo of Egypt.

    Science.gov (United States)

    Ibrahim, Alshaymaa Ahmed; El-Lebedy, Dalia; Ashmawy, Ingy; Hady, Maha Abdel

    2017-06-01

    Paraoxonase-1 (PON1) is involved in the oxidative stress process that cause tissue damage observed in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). The aim of the present study was to investigate the association of PON1 Q192R and L55M polymorphisms with risk of SLE and associated APS among Egyptian sample. The study included 120 SLE patients (45 without APS and 75 with APS) and 120 healthy subjects. PON1 Q192R and L55M polymorphisms were genotyped by real-time PCR. No significant differences in Q192R genotypes or allele frequencies were found between patients and controls (p = 0.5 and 0.1, respectively). The frequency of the 55M allele was significantly higher in SLE patients than in controls (66.6 vs. 43.3%), while the 55L allele was more frequent in controls (56.6%) than in patients (33.3%) (p = 0.03). The LL genotype was more frequent in controls (21.6%) than in patients (10%) while M allele carrier genotypes (LM + MM) were more frequent among patients (90%) than controls (78.3%), p = 0.04. Also, the 55M allele was more frequent in APS patients (73.3%) than in patients without APS (55.6%), p = 0.004. M allele carrier genotypes (LM + MM) was significantly higher among APS patients (95.4%) than in non-APS patients (80%), p = 0.008. Our results indicated that the PON1 L55M polymorphism associated with SLE and associated APS in a population from Cairo of Egypt, while the Q192R polymorphism plays no role in disease susceptibility. A large scale study to assess PON1 polymorphisms, PON1 activity, and markers of oxidative stress interaction is needed to clarify the role of PON-1 polymorphisms in the pathogenesis of SLE and associated APS.

  18. 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.

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

    Science.gov (United States)

    Scherrer, Daniel Zanetti; Zago, Vanessa Helena de Souza; Vieira, Isabela Calanca; Parra, Eliane Soler; Panzoldo, Natália Baratella; Alexandre, Fernanda; Secolin, Rodrigo; Baracat, Jamal; Quintão, Eder Carlos Rocha; de Faria, Eliana Cotta

    2015-01-01

    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 < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques. 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. PMID:26039660

  20. 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.

  1. Phospho-Pon Binding-Mediated Fine-Tuning of Plk1 Activity.

    Science.gov (United States)

    Zhu, Kang; Shan, Zelin; Zhang, Lu; Wen, Wenyu

    2016-07-06

    In Drosophila neuroblasts (NBs), the asymmetrical localization and segregation of the cell-fate determinant Numb are regulated by its adaptor Partner of Numb (Pon) and the cell-cycle kinase Polo. Polo phosphorylates the Pon localization domain, thus leading to its basal distribution together with Numb, albeit through an unclear mechanism. Here, we find that Cdk1 phosphorylates Pon at Thr63, thus creating a docking site for the Polo-box domain (PBD) of Polo-like kinase 1 (Plk1). The crystal structure of the Plk1 PBD/phospho-Pon complex reveals that two phospho-Pon bound PBDs associate to form a dimer of dimers. We provide evidence that phospho-Pon binding-induced PBD dimerization relieves the autoinhibition of Plk1. Moreover, we demonstrate that the priming Cdk1 phosphorylation of Pon is important for sequential Plk1 phosphorylation. Our results not only provide structural insight into how phosphoprotein binding activates Plk1 but also suggest that binding to different phosphoproteins might mediate the fine-tuning of Plk1 activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. CYP/PON genetic variations as determinant of organophosphate ...

    Indian Academy of Sciences (India)

    as serum cholinesterase, acetylcholinesterase (Mileson et al. 1998) and ..... human serum. Figure 3. (a) PON1 protein and SNPs with their effect. (b) SNPs of PON1 and PON2 genes. The rs662, rs7493, rs12026 SNPs are present on chromosome 7:94937446, ..... typing of various sequence variants and by using sensitive.

  3. 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.

  4. 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; p<0.001), lower CLP (80.58 vs. 97.98U/L; p=0.032), lower MPO (91.24 vs. 116.55U/L; p=0.023), and higher CAT levels (256.5 vs.145.5kU/L; p=0.003) were determined in the sepsis 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.

  5. Somatotopic location of corticospinal tract at pons in human brain: a diffusion tensor tractography study.

    Science.gov (United States)

    Hong, Ji Heon; Son, Su Min; Jang, Sung Ho

    2010-07-01

    No diffusion tensor tractography (DTT) study has yet investigated the somatotopic location of the corticospinal tract (CST) at the pons. In the current study, we used DTT to investigate the somatotopic location of the CST at the pons in the human brain. We recruited 25 healthy volunteers for this study. Diffusion tensor images (DTIs) were scanned using 1.5-T; CSTs for the hand and leg were obtained using FMRIB software. Normalized DTT was reconstructed using the Montreal Neurological Institute echo-planar imaging template supplied with the SPM. Individual DTI data were calculated as a pixel unit at the upper and lower pons. Relative average location of the highest probability point of the CST for the hand was 47.70%, with the standard from the midline to the most lateral point of the upper pons, and 35.87% at the lower pons. For the leg, the CST was located at 56.82% at the upper pons and 40.63% at the lower pons. For the anteroposterior direction from the most anterior point of the pons to the most anterior point of the fourth ventricle, the CST for the hand was located at 42.30% at the upper pons and 36.18% at the lower pons. For the leg, the CST was located at 45.68% and 39.01%, respectively. We found that the hand somatotopy of the CST was located at the antero-medial portion at the pons and that the leg somatotopy of the CST was located postero-laterally to the hand somatotopy of the CST. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  6. Near-infrared heat lamp therapeutic effect on paraoxonase 1 and myeloperoxidase as potential biomarkers of redox state changes induced by γ-irradiation in albino rats.

    Science.gov (United States)

    Abdel-Magied, N; Ahmed, A G; Shedid, S M

    2018-02-01

    Infrared radiation has a potential therapeutic effect in some diseases. The aim of this study was to estimate the therapeutic role of near infrared heat lamp (NIRHL) on the variations of the activity of paraoxonase 1 (PON1) and myeloperoxidase (MPO), in relation to lipid disorders, associated with oxidative stress in rats gamma-irradiated. In addition, study the effect of the duration of NIRHL treatment. Animals were divided into six groups. The results revealed that irradiated rats treated with NIRHL 20 min/once/day showed positive modulation of PON1 and MPO linked to significant improvement of lipid disorders evidenced by lower triglycerides, low density lipoprotein cholesterol (LDL-C), oxidized low density lipoprotein cholesterol (oxLDL-C) and higher density lipoprotein cholesterol (HDL-C) as well as significant amelioration of redox state, manifested by markedly increase of glutathione (GSH) content, total antioxidant capacity (TAC) associated with a noticeable decrease of pro-inflammatory cytokines. (TNF-α, IL-1 beta and IL-6), nitric oxide (NO), nitric oxide synthase (NOs), malondialdehyde (MDA), compared to irradiated rats. The results showed also that the NIRHL treatment for 20 min/twice/day had negative effects on the previous parameters and on the behavior of rats such as itching, irritability, dyspnea and death in normal as well as, irradiated rats. In conclusion, the results in this study show that NIRHL therapy for a short time can effectively prevent the lipid disorders induced by radiation through the positive modulation mechanism of PON1 and MPO enzymes and improvement of oxidative stress. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Association between PON1 genetic polymorphisms and miscarriage in Mexican women exposed to pesticides.

    Science.gov (United States)

    Blanco-Muñoz, Julia; Aguilar-Garduño, Clemente; Gamboa-Avila, Ricardo; Rodríguez-Barranco, Miguel; Pérez-Méndez, Oscar; Huesca-Gómez, Claudia; González-Alzaga, Beatriz; Lacasaña, Marina

    2013-04-01

    Placental oxidative stress has been involved in the pathogenesis of certain reproductive adverse effects, including miscarriage. Paraxonase 1 (PON1) is a high-density lipoprotein(HDL)-linked enzyme that prevents oxidation of low-density lipoproteins (LDL) and is involved in detoxification from organophosphate pesticides. To assess the association between maternal PON1 polymorphisms (PON1192Q/R, PON155 L/M y PON1-108C/T) and the risk of miscarriage in women chronically exposed to organophosphate pesticides in Mexico. In a cross-sectional study, socio-demographic data, reproductive history data, environmental exposures, and other variables of concern were collected by means of a questionnaire from 264 women (floriculturists and wives of floriculturists) who had been pregnant sometime during the 10 years preceding the study. Blood samples were also collected from them. PON1192 and PON155 genotypes were determined by PCR amplification, and PON1-108 genotypes, by a TaqMan real-time polymerase chain reaction assay. Complete information regarding the results of pregnancy and maternal genotype tests was obtained for 514 pregnancies (35 miscarriages and 479 controls). The association between PON1 genotypes and miscarriage was evaluate through GEE models. The risk of miscarriage by mothers with PON1192RR genotype was 2.2 higher than by mothers with PON1192QR/PON1192QQ genotype (95% CI 0.93-5.17). The risk was close to 4 times higher in mothers with PON155MM/PON155LM genotype than in mothers with PON155LL genotype (OR=3.9; 95% CI 1.38-11.0). No significant differences were found in risk of miscarriage based on the maternal PON1-108C/T genotype. No evidence was found of an interaction between the various PON1 genotypes and the mothers' floricultural activity during pregnancy. This study suggests that there is an effect of genetic maternal PON1 polymorphisms on miscarriage and provides additional evidence that combines with the growing information about the ways in which

  8. [Relationship between Q192R polymorphisms in paraoxonase 1 gene and young ischemic stroke].

    Science.gov (United States)

    Liu, Jing-li; Li, Jin-pin; Wang, Xiao-ling; Yang, Yi

    2010-04-06

    To investigate the relationship between polymorphisms in paraoxonase1 (PON1) gene Gln192Arg (Q192R) and arterial ischemic stroke in young adults. The Q192R genotype was analyzed by polymerase chain reaction in 131 young adults with ischemic stroke and 135 age- and gender-matched controls. The plasma lipids were also determined in patients and controls respectively. Furthermore, carotid artery intima-media thickness (IMT) in patients were measured by carotid ultrasonography. The distributions of Q192R genotype frequency were significantly different between patients with ischemic stroke and control individuals. And the patients had more RR genotypes than control individuals (P stroke were 1.743 (95% confidence interval [CI], 1.032-2.943) in subjects with RR genotype. We also studied the relationship between the polymorphisms and the lipid concentration in patients and control individuals. However, no significant association was detected between Q/R192 genotype and any of lipid measurements. Further, the prevalence of cigarette smoking, hypertension and diabetes showed no significant difference between RR and non-RR genotypes in patients. Body mass index (BMI) in two groups did not differ significantly. But IMT of patients with RR genotype obviously increased in comparison to those without RR genotype (P ischemic stroke in young adults. RR genotype is a genetic risk for young adults with ischemic stroke through an increased carotid artery intima-media thickness and an accelerated atherosclerotic process.

  9. SERUM PARAOXONASE ACTIVITY IN RENAL TRANSPLANT RECIPIENTS

    Directory of Open Access Journals (Sweden)

    Saritha Gadicherla

    2017-12-01

    Full Text Available BACKGROUND Serum paraoxonase is an enzyme synthesised in the liver. It is known to prevent atherosclerosis by inhibiting oxidation of lowdensity lipoprotein. Renal transplant recipients have increased tendency for developing atherosclerosis and cardiovascular disease. Reduced activity of serum paraoxonase contributes to accelerated atherosclerosis and increased cardiovascular complications in these patients. The aim of this study was to estimate serum paraoxonase activity in renal transplant recipients and compare it with healthy controls. MATERIALS AND METHODS 30 renal transplant recipients and 30 age and sex matched healthy controls were taken for the study. Serum paraoxonase activity, blood urea, serum creatinine and uric acid were estimated in these groups. The serum paraoxonase activity was correlated with urea, creatinine and uric acid levels. RESULTS Serum paraoxonase activity was reduced in renal transplant recipients compared to healthy controls. There was a negative correlation between paraoxonase activity and the levels of urea, creatinine and uric acid levels. CONCLUSION In this study, the paraoxonase activity was reduced in renal transplant recipients compared to controls. The increased cardiovascular disease in these patients could be due to reduced paraoxonase activity.

  10. Paraoxonase activity in athletic adolescents.

    Science.gov (United States)

    Cakmak, Alpay; Zeyrek, Dost; Atas, Ali; Erel, Ozcan

    2010-02-01

    Regular physical activity may play a protective role against cardiovascular disease in adults, and paraoxonase activity may serve to mediate this effect. This study compared paraoxonase activity and that of other antioxidative agents in adolescent athletes compared with inactive youth. Paraoxonase level was 177.32 +/- 100.10 (U/L) in children with regular physical activity and 98.11 +/- 40.92 (U/L) in the control group (P total antioxidative capacity, total oxidative status, oxidative stress index, and lipid hydroperoxide were significantly higher in the athlete group compared with controls (P < 0.0001). Paraoxonase activity was found to be greater in adolescent athletes, suggesting that regular exercise might provide a cardio-protective effect by this means.

  11. 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

  12. Oxidative status and paraoxonase activity in children with asthma.

    Science.gov (United States)

    Cakmak, Alpay; Zeyrek, Dost; Atas, Ali; Selek, Sahabettin; Erel, Ozcan

    2009-10-01

    To compare paraoxonase activity and changes in oxidative status in asthmatic children and healthy children by determining serum paraoxonase activity and total oxidative status, total antioxidant capacity and lipid hydroperoxidation. Forty two asthmatic children were compared with 32 healthy children of similar age and sex. To evaluate the paraoxonase and oxidative status, total antioxidant capacity and lipid hydroperoxidation were examined. Serum paraoxonase activity was evaluated by measuring the rate of paraoxon hydrolosis. Oxidative status was evaluated by the method developed by Erel. Lipid hydroperoxide was measured by an iodometric method. In comparison with the healthy control group, the paraoxonase activity of the asthmatic children was found to be low (163.7 +/- 73.0 (U/L) and 349.2 +/- 153.9 (U/L), P = 0.002) and total oxidant status (9.0 +/- 3.5 micromol H2O2 Eq/L and 13.4 +/- 7.0 micromol H2O2 Eq/L, P =0.002), total antioxidant capacity (5.5 +/- 2.5 micromol Trolox Eq/L and 1.0 +/- 0.6 micromol Trolox Eq/L, P total oxidant status, total antioxidant capacity and lipid hydroperoxidation levels increase, paraoxonase activity decreased.

  13. PON1 promoter polymorphisms contribute to PCOS susceptibility and phenotypic outcomes in Indian women.

    Science.gov (United States)

    Dadachanji, Roshan; Shaikh, Nuzhat; Patil, Anushree; Shah, Nalini; Mukherjee, Srabani

    2018-06-30

    Polycystic ovary syndrome is a common endocrinopathy characterized by anovulatory infertility, hyperandrogenism, insulin resistance and oxidative stress, which predisposes affected women to reproductive and cardiometabolic complications in later life. We have investigated the association of PON1 promoter polymorphisms with PCOS susceptibility, PON1 activity and its related traits in Indian women. The genotypic and allelic frequency distribution of only -907G/C polymorphism in PON1 promoter showed significant difference between non-hyperandrogenic control and PCOS women, and was significantly associated with reduced susceptibility to PCOS, considering the recessive model. PON1 lactonase and arylesterase activities were also significantly decreased in women with PCOS compared to controls. Further, PON1 promoter polymorphisms were linked to altered insulin and testosterone levels in hyperandrogenic and non-hyperandrogenic women with PCOS. This study highlights PON1 as an important candidate gene influencing genetic pathophysiology of PCOS. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    African Journals Online (AJOL)

    SERVER

    2008-03-04

    2000). ... Playfer JR, Eze CL, Bullen MF, Evans DAP (1976). Genetic polymor- phism and interethnic variability of plasma paraoxonase activity. J. Med. ... Senter PD, Marquardt H, Thomas BA, Hammock BD, Frank IS,. Svensson ...

  15. The neuroprotective effect of lovastatin on MPP(+)-induced neurotoxicity is not mediated by PON2.

    Science.gov (United States)

    Aguirre-Vidal, Yoshajandith; Montes, Sergio; Tristan-López, Luis; Anaya-Ramos, Laura; Teiber, John; Ríos, Camilo; Baron-Flores, Verónica; Monroy-Noyola, Antonio

    2015-05-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of the pigmented dopaminergic neurons in the substantia nigra pars compacta with subsequent striatal dopamine (DA) deficiency and increased lipid peroxidation. The etiology of the disease is still unclear and it is thought that PD may be caused by a combination of genetic and environmental factors. In the search of new pharmacological options, statins have been recognized for their potential application to treat PD, due to their antioxidant effect. The aim of this work is to contribute in the characterization of the neuroprotective effect of lovastatin in a model of PD induced by 1-methyl-4-phenylpyridinium (MPP(+)). Male Wistar rats (200-250 g) were randomly allocated into 4 groups and administered for 7 days with different pharmacological treatments. Lovastatin administration (5 mg/kg) diminished 40% of the apomorphine-induced circling behavior, prevented the striatal DA depletion and lipid peroxides formation by MPP(+) intrastriatal injection, as compared to the group of animals treated only with MPP(+). Lovastatin produced no change in paraoxonase-2 (PON2) activity. It is evident that lovastatin conferred neuroprotection against MPP(+)-induced protection but this effect was not associated with the induction of PON2 in the rat striatum. Copyright © 2015. Published by Elsevier B.V.

  16. A Possible Mechanism: Vildagliptin Prevents Aortic Dysfunction through Paraoxonase and Angiopoietin-Like 3

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    2018-01-01

    Full Text Available The collected data have revealed the beneficial effects of dipeptidyl peptidase-4 (DPP-4 inhibitors on the vascular endothelium, including vildagliptin. However, the involved mechanisms are not yet clear. In this study, Sprague-Dawley rats were randomly divided into the following four groups: control, diabetic, diabetic + low-dose vildagliptin (10 mg/kg/d, and diabetic + high-dose vildagliptin (20 mg/kg/d. The diabetic model was created by feeding a high-fat diet for four weeks and injection of streptozotocin. Then, vildagliptin groups were given oral vildagliptin for twelve weeks, and the control and diabetic groups were given the same volume of saline. The metabolic parameters, endothelial function, and whole genome expression in the aorta were examined. After 12 weeks of treatment, vildagliptin groups showed significantly reduced blood glucose, blood total cholesterol, and attenuated endothelial dysfunction. Notably, vildagliptin may inhibit angiopoietin-like 3 (Angptl3 and betaine-homocysteine S-methyltransferase (Bhmt expression and activated paraoxonase-1 (Pon1 in the aorta of diabetic rats. These findings may demonstrate the vasoprotective pathway of vildagliptin in vivo.

  17. 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: ... were diagnosed and treated for T2DM (fasting blood glucose > 126 ... fossa and axilla by continuous grey-scale imaging with a linear,.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Epigenetic patterns of two gene promoters (TNF-α and PON) in stroke considering obesity condition and dietary intake.

    Science.gov (United States)

    Gómez-Uriz, A M; Goyenechea, E; Campión, J; de Arce, A; Martinez, M T; Puchau, B; Milagro, F I; Abete, I; Martínez, J A; Lopez de Munain, A

    2014-06-01

    Some causal bases of stroke remain unclear, but the nutritional effects on the epigenetic regulation of different genes may be involved. The aim was to assess the impact of epigenetic processes of human tumor necrosis factor (TNF-α) and paraoxonase (PON) promoters in the susceptibility to stroke when considering body composition and dietary intake. Twenty-four patients (12 non-stroke/12 stroke) were matched by sex (12 male/12 female), age (mean 70 ± 12 years old), and BMI (12 normal-weight/12 obese; mean 28.1 ± 6.7 kg/m(2)). Blood cell DNA was isolated and DNA methylation levels of TNF-α (-186 to +349 bp) and PON (-231 to +250 bp) promoters were analyzed by the Sequenom EpiTYPER approach. Histone modifications (H3K9ac and H3K4me3) were analyzed also by chromatin immunoprecipitation in a region of TNF-α (-297 to -185). Total TNF-α promoter methylation was lower in stroke patients (p stroke patients (r = 0.72; p = 0.008). The +309 CpG methylation site from TNF-α promoter was related to body weight (p = 0.027) and the region containing three CpGs (from -170 to -162 bp) to the percentage of lipid intake and dietary indexes (p stroke patients. The methylation of PON +15 and +241 CpGs was related to body weight (p = 0.021), waist circumference (p = 0.020), and energy intake (p = 0.018), whereas +214 was associated to the quality of the diet (p stroke patients. When comparing stroke vs non-stroke patients regarding the histone modifications analyzed at TNF-α promoter, no changes were found, although a significant association was identified between circulating TNF-α level and H3K9ac with H3K4me3. TNF-α and PON promoter methylation levels could be involved in the susceptibility to stroke and obesity outcome, respectively. The dietary intake and body composition may influence this epigenetic regulation in non-stroke patients.

  20. N Pon Saravanan

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. N Pon Saravanan. Articles written in Resonance – Journal of Science Education. Volume 9 Issue 1 January 2004 pp 6-11 General Article. Indoor Air Pollution - Danger at Home · N Pon Saravanan · More Details Fulltext PDF ...

  1. Alteration of paraoxonase, arylesterase and lactonase activities in people around fluoride endemic area of Tamil Nadu, India.

    Science.gov (United States)

    Arulkumar, Mani; Vijayan, Raji; Penislusshiyan, Sakayanathan; Sathishkumar, Palanivel; Angayarkanni, Jayaraman; Palvannan, Thayumanavan

    2017-08-01

    Toxicity due to excess fluoride concentration in drinking water is of great concern in people who rely only on the ground water as their water source in many region of the world. We collected samples and examined the toxicity of fluoride in a population residing at Salem, Dharmapuri and Krishnagiri districts of Tamil Nadu, India and measured HDL bound enzyme (PON1), erythrocyte membrane bound enzymes (acetylcholinesterase, AChE) and adenosine 5' triphosphatase (ATPases), plasma enzyme (butyrylcholinesterase, BChE) and rate limiting enzyme in heme biosynthesis (delta aminolevulinic acid dehydratase, δ-ALAD) activities. In fluorosis patients, formation of lipid peroxidation product was more in erythrocytes than in plasma. The observation further revealed that there was 50% reduction in the activity of HDL bound anti atherogenic enzyme-paraoxonase (PON1). The activities of membrane bound and signaling enzymes (acetylcholinesterase - AChE and adenosine 5' triphosphatase - ATPase) of erythrocyte were also diminished. These results suggested that there was defectiveness in the signaling and energy metabolism in fluorosis patients. Altered isoenzyme pattern of lactate dehydrogenase (LDH) in fluorosis samples was observed. Furthermore, the result suggested that both the heart (LDH 1) and liver (LDH 5) were most affected by fluoride toxicity. The study also provided reference values for tests which are used to predict the severity of fluoride toxicity. The toxic effect of fluoride was due to the collective effects on vital protective system rather than single factor. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Effects of Pomegranate peel hydroAlcoholic extract and vitamin E supplementation on Paraoxonase, myeloperoxidase Activities and nitric oxide levels following an exhaustive exercise in rats

    Directory of Open Access Journals (Sweden)

    Saeid Veiskarami

    2017-03-01

    Full Text Available Background: free radicals produced as a result of heavy training exercise especially oxygen species (ROS damage to body tissues Which can be prevent from this by consuming antioxidant substances timely. The aim of this study was to evaluate effect of Pomegranate (Punica Granatum peel hydro alcoholic on reduced of oxidative stress induced by an exhaustive exercise. Materials and Methods: Thirty two weight-matched male Wistar rats were evenly divided into: 1 control: received saline (0.2 ml saline/ rat by oral administration via epigastric tube. 2 Received oral administration of 200 mg/kg pomegranate peel hydro alcoholic extract (PPHE200. 3 Received oral administration of 250 mg/kg Pomegranate peel hydro alcoholic extract (PPHE250. 4 Received oral administration of vitamin E (vit E 5 mg/kg. Animals were submitted to swimming exhaustive exercise stress for an 8-week. At the end of the experiment, blood samples were collected for serum. Serum samples were analyzed for paraoxonase-1(PON-1 and myeloperoxidase (MPO activities and nitric oxide levels. Results: Paraoxonase-1 (PON-1 activities serum were significantly increases in PPHE200 (23.03±1.47, PPHE250 (23.59±1.98 and vit E (25.38±2.65 than in the control (18.57±1.380 (p<0.05.In PPHE200 (32.76±9.97 ،PPHE250 (31.45±6.05 and vit E (24.94±4.65 treated animals was determined in serum where myeloperoxidase activities reduced significantly compared with control (40.70±6.14 (p<0.05. Levels of Nitric oxide levels were significantly lower in PPHE 200 (46.59±2.48, PPHE250 (40.27±2.62 and vit E (36.25±3.82 treated than in control (47.18±5.36 (p<0.05. Conclusion: Results indicated that Pomegranate peel hydro alcoholic extract supplementations can strength antioxidant defense system and anti-inflammatory induced by exhaustive exercise.

  3. Polymorphisms in xenobiotic metabolizing genes (EPHX1, NQO1 and PON1) in lymphoma susceptibility: a case control study

    International Nuclear Information System (INIS)

    Conesa-Zamora, Pablo; Vicente, Vicente; Pérez-Guillermo, Miguel; Ruiz-Cosano, Javier; Torres-Moreno, Daniel; Español, Ignacio; Gutiérrez-Meca, María D; Trujillo-Santos, Javier; Pérez-Ceballos, Elena; González-Conejero, Rocío; Corral, Javier

    2013-01-01

    The interplay between genetic susceptibility and carcinogenic exposure is important in the development of haematopoietic malignancies. EPHX1, NQO1 and PON1 are three genes encoding proteins directly involved in the detoxification of potential carcinogens. We have studied the prevalence of three functional polymorphisms affecting these genes rs1051740 EPHX1, rs1800566 NQO1 and rs662 PON1 in 215 patients with lymphoma and 214 healthy controls. Genotype frequencies for EPHX and NQO1 polymorphisms did not show any correlation with disease. In contrast, the GG genotype in the PON1 polymorphism was found to be strongly associated with the disease (15.3% vs. 4.7%; OR = 3.7 CI (95%): 1.8-7.7; p < 0.001). According to the pathological diagnosis this association was related to follicular (p = 0.004) and diffuse large B-cell (p = 0.016) lymphomas. Despite the fact that further confirmation is needed, this study shows that the PON1 GG genotype in rs662 polymorphism could be a risk factor for B-cell lymphomas

  4. Crystal structures of the transpeptidase domain of the Mycobacterium tuberculosis penicillin-binding protein PonA1 reveal potential mechanisms of antibiotic resistance.

    Science.gov (United States)

    Filippova, Ekaterina V; Kieser, Karen J; Luan, Chi-Hao; Wawrzak, Zdzislaw; Kiryukhina, Olga; Rubin, Eric J; Anderson, Wayne F

    2016-06-01

    Mycobacterium tuberculosis is a human respiratory pathogen that causes the deadly disease tuberculosis. The rapid global spread of antibiotic-resistant M. tuberculosis makes tuberculosis infections difficult to treat. To overcome this problem new effective antimicrobial strategies are urgently needed. One promising target for new therapeutic approaches is PonA1, a class A penicillin-binding protein, which is required for maintaining physiological cell wall synthesis and cell shape during growth in mycobacteria. Here, crystal structures of the transpeptidase domain, the enzymatic domain responsible for penicillin binding, of PonA1 from M. tuberculosis in the inhibitor-free form and in complex with penicillin V are reported. We used site-directed mutagenesis, antibiotic profiling experiments, and fluorescence thermal shift assays to measure PonA1's sensitivity to different classes of β-lactams. Structural comparison of the PonA1 apo-form and the antibiotic-bound form shows that binding of penicillin V induces conformational changes in the position of the loop β4'-α3 surrounding the penicillin-binding site. We have also found that binding of different antibiotics including penicillin V positively impacts protein stability, while other tested β-lactams such as clavulanate or meropenem resulted in destabilization of PonA1. Our antibiotic profiling experiments indicate that the transpeptidase activity of PonA1 in both M. tuberculosis and M. smegmatis mediates tolerance to specific cell wall-targeting antibiotics, particularly to penicillin V and meropenem. Because M. tuberculosis is an important human pathogen, these structural data provide a template to design novel transpeptidase inhibitors to treat tuberculosis infections. Structural data are available in the PDB database under the accession numbers 5CRF and 5CXW. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  5. 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.

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

    International Nuclear Information System (INIS)

    Atamer, Y.; Atamer, A.; Can, A.S.; Hekimoğlu, A.; Ilhan, N.; Yenice, N.; Koçyiğit, Y.

    2013-01-01

    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 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

  7. Performance comparison of a wdm pon with tdm pon at 10 gbps

    International Nuclear Information System (INIS)

    Usman, M.

    2014-01-01

    Recent developments in optical technologies have realized wavelength division multiplexed passive optical network (WDM PON) as a promising and a cost-effective solution for the next generation networks. Due to the intrinsic optical transparency and extremely high transmission capacity, WDM PON is considered more future oriented than conventional TDM PON. In this paper we compare an eight channel WDM PON with an eight channel TDM PON, both operating at 10 Gbps data rate. Network parameters like input laser power, optical fiber length and optical amplifier gain are varied and their impact on performance parameters i.e. Q-factor, BER, OSNR, Eye opening and Extinction ratio penalty is recorded. Results reveal that WDM PON exhibits superior performance than TDM PON in each case. (author)

  8. Effects of extremely low frequency electromagnetic fields on paraoxonase serum activity and lipid peroxidation metabolites in rat.

    Science.gov (United States)

    Seifirad, Soroush; Farzampour, Shahrokh; Nourbakhsh, Mitra; Amoli, Mahsa Mohammad; Razzaghy-Azar, Maryam; Larijani, Bagher

    2014-01-01

    Atherogenic effects of ELF-MF exposure have not been studied well so far. Therefore we have hypothesized that ELF-MF exposure might have atherogenic effect by impairing antioxidant function and increasing lipid peroxidation. This study was therefore undertaken to examine the effects of ELF-MF on paraoxonase (PON) activity, antioxidant capacity and lipid peroxidation metabolites. Effects of time on remodeling of antioxidant system were also investigated in this study. Seventy five Wistar rats were randomly allocated into five groups as follows: 1) Sham exposure, 2) Single exposure to 60 Hz, sacrificed immediately after exposure, 3) Single exposure to 60 Hz, sacrificed 72 hours after exposure, 4) Fourteen days of exposure to 60 Hz, sacrificed immediately after exposure, and 5) Fourteen days of exposure to 60 Hz, sacrificed 72 hours after exposure. Blood samples were collected and analyzed. The results were compared using ANOVA and post hoc Tukey HSD for multiple caparisons. Single ELF-MF exposure significantly increased lipid peroxidation (CD and MDA) and increased antioxidant serum activity (HDL, paraoxonase activity, and serum total antioxidant capacity). Chronic ELF-MF exposure increased lipid peroxidation and affected antioxidant system. Free fatty acids levels were significantly increased after both single and two weeks exposure. Chronic exposure led to irreversible changes while acute exposure tended to reversible alterations on above mentioned parameters. According to the results of this study, ELF-MF exposure could impair oxidant-antioxidant function and might increase oxidative stress and lipid peroxidation. Antioxidant capability was dependent on the duration and continuity of ELF-MF exposure.

  9. 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.

  10. International Conference: Paraoxonases - Basic and Clinical Directions of Current Research (1st) Held in Ann Arbor, Michigan on April 22-24, 2004

    National Research Council Canada - National Science Library

    Weber, Wendell W

    2005-01-01

    .... PON 1 hydrolyzed cholesteryl linoleate hydroperoxides (CL-OOH) in oxidized LDL, HDL and macrophages and in human and mice atherosclerotic coronary or carotid lesions, yielding in the formation of linoleic acid hydroperoxides (L-OOH...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Paraoxonase activity in liver of Pacu, Piaractus mesopotamicus Holmberg (Characidae

    Directory of Open Access Journals (Sweden)

    Vera Lucia F. Cunha Bastos

    1998-01-01

    Full Text Available Enzymatic production of p-nitrophenol in liver of Piaractus mesopotamicus Holmberg, 1887 was consistently assayed at pH 8.5 using 7.5 mM paraoxon as substrate. This pacu liver paraoxonase activity was activated by NaCl. Apparent values of K M were 2.42 x 10-3 M in the presence of 0.5 M NaCl and 8.99 x 10-3 M without NaCl. Apparent maximum velocity values calculated in the absence and presence of 0.5 M NaCl were 1.09 x 10-3 µmoles/min/mg of proteins and 1.29 x 100-3 µmoles/min/mg of proteins, respectively. These Vmax values are fifty-fold the value described for trout (Salmo trutta Linnaeus, 1758 liver paraoxonase. Paraoxonase activity of pacu liver homogenates was recovered as much in cytosolic as in particulate cellular subtractions, but the particulate subtractions showed higher specific activities. The data presented here indicate that hepatic hydrolysis of organophosphorous pesticides may not be an important detoxification process in pacu.

  13. Bidirectional multi-optical line terminals incorporated converged WSN-PON network using M/M/1 queuing

    Science.gov (United States)

    Kumar, Love; Sharma, Vishal; Singh, Amarpal

    2017-12-01

    Wireless Sensor Networks (WSNs) have an assortment of application areas, for instance, civil, military, and video surveillance with restricted power resources and transmission link. To accommodate the massive traffic load in hefty sensor networks is another key issue. Subsequently, there is a necessity to backhaul the sensed information of such networks and prolong the transmission link to access the distinct receivers. Passive Optical Network (PON), a next-generation access technology, comes out as a suitable candidate for the convergence of the sensed data to the core system. The earlier demonstrated work with single-OLT-PON introduces an overloaded buffer akin to video surveillance scenarios. In this paper, to combine the bandwidth potential of PONs with the mobility capability of WSNs, the viability for the convergence of PONs and WSNs incorporating multi-optical line terminals is demonstrated to handle the overloaded OLTs. The existing M/M/1 queue theory with interleaving polling with adaptive cycle time as dynamic bandwidth algorithm is used to shun the probability of packets clash. Further, the proposed multi-sink WSN and multi-OLT PON converged structure is investigated in bidirectional mode analytically and through computer simulations. The observations establish the proposed structure competent to accommodate the colossal data traffic through less time consumption.

  14. Influence on serum asymmetric dimethylarginine (ADMA) concentrations of human paraoxonase 1 polymorphism (Q192R) and exposure to polycyclic aromatic hydrocarbons (PAHs) in Mexican women, a gene-environment interaction.

    Science.gov (United States)

    Ochoa-Martínez, Ángeles C; Ruíz-Vera, Tania; Almendarez-Reyna, Claudia I; Orta-García, Sandra T; Pérez-Maldonado, Iván N

    2017-11-01

    It has been demonstrated that Cardiovascular Diseases (CVD) are a consequence of the combination of genetic and environmental factors and/or the interaction between them. Therefore, the aim of this study was to evaluate the impact of polycyclic aromatic hydrocarbon (PAHs) exposure and PON1 Q192R polymorphism (genetic susceptibility) on serum asymmetric dimethylarginine (ADMA) levels in Mexican women (n = 206). Urinary 1-hydroxypyrene concentrations (1-OHP; exposure biomarker for PAHs) were quantified using a high-performance liquid chromatography technique, PON1 Q192R polymorphism was genotyped using TaqMan probes and serum ADMA concentrations were evaluated using a commercially available ELISA kit. Urinary 1-OHP levels detected in this study ranged from 0.07 to 9.37 μmol/mol of creatinine (0.13-18.0 μg/g of creatinine). Regarding allele frequency (PON1 Q192R polymorphism), the 192Q-allele frequency was 0.43 and for the 192R-allele it was 0.57. In relation to serum ADMA levels, the levels ranged from 0.06 to 1.46 μmol/L. Moreover, multiple linear regression analysis was performed and associations between urinary 1-OHP levels (β = 0.05, p = 0.002), PON1 Q192R polymorphism (β = 0.04, p = 0.003) and serum ADMA concentrations were found. Besides, an interaction (gene-environment interaction) of both independent variables (1-OHP and PON1 polymorphism) on serum ADMA levels was found (β = 0.04, p = 0.02) in the constructed multiple linear model. Therefore, according to the significance of this research, it is necessary to execute health programs to reduce cardiovascular risk in the assessed population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Effect of moxifloxacin on oxidative stress, paraoxonase-1 (PON1 ...

    African Journals Online (AJOL)

    oxidative stress in patients with multiple drug-resistant tuberculosis (MDR-TB). Methods: A total ofof ... seriously affects the quality of life and prognosis. [6]. ... balance between pro-oxidants and antioxidant ..... original work is properly credited.

  16. 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 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.

  17. Association of genetic polymorphisms of PON1 and CETP with the ...

    African Journals Online (AJOL)

    ... with an increased risk of cardiovascular disease and type 2 diabetes. PON1 and CETP genes may be involved in the pathogenesis of lipid metabolism and thus MetS. Several single nucleotide polymorphisms of genes were demonstrated to affect their function. Curcumin (diferuloylmethane) is a yellow pigment of turmeric ...

  18. Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis

    International Nuclear Information System (INIS)

    Klinger, K.W.; Winqvist, R.; Riccio, A.

    1987-01-01

    The regional chromosomal location of the human gene for plasminogen activator inhibitor type 1 (PAI1) was determined by three independent methods of gene mapping. PAI1 was localized first to 7cen-q32 and then to 7q21.3-q22 by Southern blot hybridization analysis of a panel of human and mouse somatic cell hybrids with a PAI1 cDNA probe and in situ hybridization, respectively. The authors frequent HindIII restriction fragment length polymorphism (RFLP) of the PAI1 gene with an information content of 0.369. In family studies using this polymorphism, genetic linkage was found between PAI1 and the loci for erythropoietin (EPO), paraoxonase (PON), the met protooncogene (MET), and cystic fibrosis (CF), all previously assigned to the middle part of the long arm of chromosome 7. The linkage with EPO was closest with an estimated genetic distance of 3 centimorgans, whereas that to CF was 20 centimorgans. A three-point genetic linkage analysis and data from previous studies showed that the most likely order of these loci is EPO, PAI1, PON, (MET, CF), with PAI1 being located centromeric to CF. The PAI1 RFLP may prove to be valuable in ordering genetic markers in the CF-linkage group and may also be valuable in genetic analysis of plasminogen activation-related diseases, such as certain thromboembolic disorders and cancer

  19. 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 (pantioxidant parameters were similar among the patients during AFP and the controls.

  20. WDM PONs based on colorless technology

    Science.gov (United States)

    Saliou, Fabienne; Simon, Gael; Chanclou, Philippe; Pizzinat, Anna; Lin, Huafeng; Zhou, Enyu; Xu, Zhiguang

    2015-12-01

    Wavelength Division Multiplexing (WDM) Passive Optical Network (PON) is foreseen to be part of the Next Generation Passive Optical Networks. Business and mobile fronthaul networks already express the need to develop WDM PONs in the access segment. Fixed wavelength transceivers based on Coarse WDM are already available to respond to today's market needs but Dense WDM technologies will be needed and colorless technologies are essential to provide simple and cost-effective WDM PON systems. We propose in this paper to demonstrate the capabilities of a DWDM PON system prototype based on self-seeded RSOAs and designed to transmit CPRI over 60 km of fiber at 2.5 Gbit/s.

  1. 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.

  2. Preparative Production of Acetylcholinesterase and Paraoxonase in Procaryotic and Eucaryotic Expression Systems

    National Research Council Canada - National Science Library

    Sussman, Joel; Silman, I

    2004-01-01

    ... (HDL, good cholesterol% and are involved in the prevention of atherosclerosis. We describe the first crystal structure of a PON family member, a variant of PON1 obtained by directed evolution, at a resolution of 2.2...

  3. Association of genetic polymorphisms of PON1 and CETP with the presence of metabolic syndrome; the effects of genotypes on their serum activity and concentrations

    Directory of Open Access Journals (Sweden)

    Behdokht Fathi Dizaji

    2018-01-01

    Conclusions: There were no associations between the PON1 polymorphisms, or haplotypes with MetS. There was an association between CETPrs5882 and metabolic syndrome. AA genotype of CETPrs5882 appeared to be protective against MetS in our studied population. There were no association between the PON1 and CETP polymorphisms with PON1enzymatic activities and CETP protein levels at base line and after curcumin supplementation.

  4. Desarrollo de algoritmos de asignación de recursos en redes de acceso PON y TWDM-PON

    OpenAIRE

    Juárez Estévez, David

    2017-01-01

    El estudio de investigación realizado y descrito en este Trabajo Fin de Grado (TFG) se ha centrado en el desarrollo de algoritmos de gestión de recursos en redes PON (Passive Optical Network) y TWDM-PON (Time Wavelength Division Multiple Passive Optical Network), cuya arquitectura está implementada en un simulador bajo el entorno de simulación OMNET++. Así pues, inicialmente, se realizó un análisis de las redes de acceso PON, además del entorno de trabajo sobre el cual se iba a realizar es...

  5. of Several Organophosphorus Insecticide Metabolites

    Directory of Open Access Journals (Sweden)

    Russell L. Carr

    2015-01-01

    Full Text Available Paraoxonase (PON1 is a calcium dependent enzyme that is capable of hydrolyzing organophosphate anticholinesterases. PON1 activity is present in most mammals and previous research established that PON1 activity differs depending on the species. These studies mainly used the organophosphate substrate paraoxon, the active metabolite of the insecticide parathion. Using serum PON1 from different mammalian species, we compared the hydrolysis of paraoxon with the hydrolysis of the active metabolites (oxons of two additional organophosphorus insecticides, methyl parathion and chlorpyrifos. Paraoxon hydrolysis was greater than that of methyl paraoxon, but the level of activity between species displayed a similar pattern. Regardless of the species tested, the hydrolysis of chlorpyrifos-oxon was significantly greater than that of paraoxon or methyl paraoxon. These data indicate that chlorpyrifos-oxon is a better substrate for PON1 regardless of the species. The pattern of species differences in PON1 activity varied with the change in substrate to chlorpyrifos-oxon from paraoxon or methyl paraoxon. For example, the sex difference observed here and reported elsewhere in the literature for rat PON1 hydrolysis of paraoxon was not present when chlorpyrifos-oxon was the substrate.

  6. Fiber to the Home Using a PON Infrastructure

    Science.gov (United States)

    Lee, Chang-Hee; Sorin, Wayne V.; Kim, Byoung Yoon

    2006-12-01

    Traffic patterns in access networks have evolved from voice- and text-oriented services to video- and image-based services. This change will require new access networks that support high-speed (> 100 Mb/s), symmetric, and guaranteed bandwidths for future video services with high-definition TV quality. To satisfy the required bandwidth over a 20-km transmission distance, single-mode optical fiber is currently the only practical choice. To minimize the cost of implementing an FTTP solution, a passive optical network (PON) that uses a point-to-multipoint architecture is generally considered to be the best approach. There are several multiple-access techniques to share a single PON architecture, and the authors addressed several of these approaches such as time-division multiple access, wavelength-division multiple access, subcarrier multiple access, and code-division multiple access. Among these multiple techniques, they focus on time-division multiplexing (TDM)-PON and wavelength-division multiplexing (WDM)-PON, which will be the most promising candidates for practical future systems. A TDM-PON shares a single-transmission channel with multiple subscribers in time domain. Then, there exists tight coupling between subscribers. A WDM-PON provides point-to-point optical connectivity using a dedicated pair of wavelengths per user. While a TDM-PON appears to be a satisfactory solution for current bandwidth demands, the combination of future data-rate projections and traffic patterns coupled with recent advances in WDM technology may result in WDM-PON becoming the preferred solution for a future proof fiber-based access network.

  7. Demonstrating TTC-PON robustness and flexibility

    CERN Document Server

    Brandao de Souza Mendes, Eduardo; Soos, Csaba; Saint-Germain, Logan; Vasey, Francois

    2018-01-01

    In 2016, a TTC-PON (Timing, Trigger and Control system based on Passive Optical Networks) demonstrator was presented at TWEPP as an alternative to replace the TTC system, currently responsible for delivering timing, trigger and control commands in the LHC experiments. Towards a deployment foreseen for ALICE phase-1 upgrade, the system has been consolidated through flexible software implementation providing full configuration, complete calibration and extended monitoring and diagnostic tools. A new demonstrator setup was built with various FPGA platforms to test the system with an increased number of nodes and under different environmental conditions. This paper focuses on the TTC-PON system design with a discussion on its features and scaled-up tests.

  8. Existing PON Infrastructure Supported Hybrid Fiber-Wireless Sensor Networks

    DEFF Research Database (Denmark)

    Yu, Xianbin; Zhao, Ying; Deng, Lei

    2012-01-01

    We propose a hybrid fiber wireless sensor network based on the existing PON infrastructure. The feasibility of remote sensing and PON convergence is experimentally proven by transmitting direct-sequence spread-spectrum wireless sensing and 2.5Gbps GPON signals.......We propose a hybrid fiber wireless sensor network based on the existing PON infrastructure. The feasibility of remote sensing and PON convergence is experimentally proven by transmitting direct-sequence spread-spectrum wireless sensing and 2.5Gbps GPON signals....

  9. 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......; or (4) control/placebo (energy-equivalent sugar-containing beverage). The treatments were given for 28 days, separated by a 4-week wash-out period. RESULTS: The PON1 activity was not affected by juice or vitamin E supplement neither was there evidence of synergetic effects. However, a statistically...

  10. Chaos-based CAZAC scheme for secure transmission in OFDM-PON

    Science.gov (United States)

    Fu, Xiaosong; Bi, Meihua; Zhou, Xuefang; Yang, Guowei; Lu, Yang; Hu, Miao

    2018-01-01

    To effectively resist malicious eavesdropping and performance deterioration, a novel chaos-based secure transmission scheme is proposed to enhance the physical layer security and reduce peak-to-average power ratio (PAPR) in orthogonal frequency division multiplexing passive optical network (OFDM-PON). By the randomly extracting operation of common CAZAC values, the specially-designed constant amplitude zero autocorrelation (CAZAC) is created for system encryption and PAPR reduction enhancing the transmission security. This method is verified in {10-Gb/s encrypted OFDM-PON with 20-km fiber transmission. Results show that, compared to common OFDM-PON, our scheme achieves {3-dB PAPR reduction and {1-dB receiver sensitivity improvement.

  11. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Estudo de topologias para redes WDM-PON

    OpenAIRE

    Guilherme Enéas Vaz Silva

    2010-01-01

    A demanda de largura de banda exigida pelos usuários de redes de acesso vem aumentando rapidamente e a rede óptica passiva baseada em multiplexação por divisão de comprimento de onda (WDM-PON) tem se destacado como a tecnologia capaz de suprir essa demanda. Dessa forma, este trabalho conduz, inicialmente, uma comparação entre uma rede WDM-PON ideal e uma rede TDM-PON, discutindo também aspectos de segurança desta última, bem como estratégias de migração entre estes dois esquemas. Devido ao cu...

  13. The Ser311Cys variation in the paraoxonase 2 gene increases the ...

    Indian Academy of Sciences (India)

    Supplementary data: The Ser311Cys variation in the paraoxonase 2 gene increases the risk of type 2 diabetes in northern Chinese. Yanchun Qu, Ze Yang, Feng Jin, Liang Sun, Chuanfang Zhang, Linong Ji, Hong Sun, Binyou Wang and Li Wang. J. Genet. 87, 165–169. Table 1. Clinical characteristics of case and control.

  14. Energy Efficiency in Future PONs

    DEFF Research Database (Denmark)

    Reschat, Halfdan; Laustsen, Johannes Russell; Wessing, Henrik

    2012-01-01

    There is a still increasing tendency to give energy efficiency a high priority, even in already low energy demanding systems. This is also the case for Passive Optical Networks (PONs) for which many different methods for saving energy are proposed. This paper uses simulations to evaluate three...... proposed power saving solutions for PONs which use sleep mechanisms for saving power. The discovered advantages and disadvantages of these methods are then used as a basis for proposing a new solution combining different techniques in order to increase the energy efficiency further. This novel solution...

  15. Highly stable bilayer of LiPON and B2O3 added Li1.5Al0.5Ge1.5(PO4) solid electrolytes for non-aqueous rechargeable Li-O2 batteries

    International Nuclear Information System (INIS)

    Jadhav, Harsharaj S.; Kalubarme, Ramchandra S.; Jadhav, Arvind H.; Seo, Jeong Gil

    2016-01-01

    Highlights: • LiPON thin film deposited by RF-sputtering technique. • The effect of deposition temperature on ionic conductivity was investigated. • The LiPON/B-LAGP composite was successfully employed in Li-O 2 battery. • LiPON interlayer enhances stability of B-LAGP in contact with Li-metal. - Abstract: Lithium ion conducting membranes are barely studied, although they are essentially indispensable for building Li-air batteries composed of aqueous and non-aqueous electrolytes for long-term operation. Lithium phosphorous oxynitride (LiPON) thin films were deposited by RF-sputtering technique on B 2 O 3 -added lithium aluminum germanium phosphate (B-LAGP). Compact thin amorphous LiPON layer could act as a protective interlayer for B-LAGP by separating it from Li metal electrode and mitigate the reaction between them. Large electrochemical stability window (0–5 V) of LiPON/B-LAGP solid electrolyte shows promising feasibility for applications in all lithium based batteries. The aprotic Li-O 2 cell with protected lithium electrode configuration employing LiPON/B-LAGP solid electrolyte has exhibited reasonable cycling stability with long-life of 52 cycles at a limited capacity of 1000 mA h g −1 .

  16. Examination of plasma PON1 paraoxonase activity and genotype in Gulf War veterans

    Science.gov (United States)

    2017-10-01

    contribute to the risk for Gulf War Illness (GWI), as defined by the Centers for Disease Control and Prevention (CDC) and Kansas case definitions in...Disease Control and Prevention (CDC) and Kansas case definitions in a large sample of GW veterans. Specifically, we will: (1) determine the...models);  clinical interventions;  new business creation; and  other. 7. PARTICIPANTS & OTHER COLLABORATING ORGANIZATIONS What

  17. Difluorophosphoryl nitrene F2P(O)N: matrix isolation and unexpected rearrangement to F2PNO.

    Science.gov (United States)

    Zeng, Xiaoqing; Beckers, Helmut; Willner, Helge; Neuhaus, Patrik; Grote, Dirk; Sander, Wolfram

    2009-12-14

    Triplet difluorophosphoryl nitrene F(2)P(O)N (X(3)A'') was generated on ArF excimer laser irradiation (lambda=193 nm) of F(2)P(O)N(3) in solid argon matrix at 16 K, and characterized by its matrix IR, UV/Vis, and EPR spectra, in combination with DFT and CBS-QB3 calculations. On visible light irradiation (lambda>420 nm) at 16 K F(2)P(O)N reacts with molecular nitrogen and some of the azide is regenerated. UV irradiation (lambda=255 nm) of F(2)P(O)N (X(3)A'') induced a Curtius-type rearrangement, but instead of a 1,3-fluorine shift, nitrogen migration to give F(2)PON is proposed to be the first step of the photoisomerization of F(2)P(O)N into F(2)PNO (difluoronitrosophosphine). Formation of novel F(2)PNO was confirmed with (15)N- and (18)O-enriched isotopomers by IR spectroscopy and DFT calculations. Theoretical calculations predict a rather long P-N bond of 1.922 A [B3LYP/6-311+G(3df)] and low bond-dissociation energy of 76.3 kJ mol(-1) (CBS-QB3) for F(2)PNO.

  18. Demonstration of flexible multicasting and aggregation functionality for TWDM-PON

    Science.gov (United States)

    Chen, Yuanxiang; Li, Juhao; Zhu, Paikun; Zhu, Jinglong; Tian, Yu; Wu, Zhongying; Peng, Huangfa; Xu, Yongchi; Chen, Jingbiao; He, Yongqi; Chen, Zhangyuan

    2017-06-01

    The time- and wavelength-division multiplexed passive optical network (TWDM-PON) has been recognized as an attractive solution to provide broadband access for the next-generation networks. In this paper, we propose flexible service multicasting and aggregation functionality for TWDM-PON utilizing multiple-pump four-wave-mixing (FWM) and cyclic arrayed waveguide grating (AWG). With the proposed scheme, multiple TWDM-PON links share a single optical line terminal (OLT), which can greatly reduce the network deployment expense and achieve efficient network resource utilization by load balancing among different optical distribution networks (ODNs). The proposed scheme is compatible with existing TDM-PON infrastructure with fixed-wavelength OLT transmitter, thus smooth service upgrade can be achieved. Utilizing the proposed scheme, we demonstrate a proof-of-concept experiment with 10-Gb/s OOK and 10-Gb/s QPSK orthogonal frequency division multiplexing (OFDM) signal multicasting and aggregating to seven PON links. Compared with back-to-back (BTB) channel, the newly generated multicasting OOK signal and OFDM signal have power penalty of 1.6 dB and 2 dB at the BER of 10-3, respectively. For the aggregation of multiple channels, no obvious power penalty is observed. What is more, to verify the flexibility of the proposed scheme, we reconfigure the wavelength selective switch (WSS) and adjust the number of pumps to realize flexible multicasting functionality. One to three, one to seven, one to thirteen and one to twenty-one multicasting are achieved without modifying OLT structure.

  19. The morphometric study of the pons and cerebellum in Korean using MRI

    International Nuclear Information System (INIS)

    Kim, Hyun Sook; Kim, Dong Ik; Yun, Mi Jin; Chung, In Hyuk; Cho, Young Kook

    1995-01-01

    To evaluate the size of normal pons and cerebellum in vivo and the change in size according to age, and to compare those with measurement of the diseased pons and cerebellum. 121 normal adults (M:F=54:67), 5 patients with OPCD and 19 patients with Wallerian degeneration were studied. The normal group was divided into 5 subgroups according to the age (ranged from 20 to 72 years). 1.5T GE Signa MR unit was used. On axial plane, the AP(A) and transverse(B) diameters of the pons, the size of the middle cerebellar peduncle(C), and transverse diameter of the posterior fossa(D) and the cerebellum(E) were measured. On midsagittal plane, the longitudinal(F) and AP(G) diameters of the basis pontis were measured. The ratios of E/D and F/G were calculated. The student t test was used for statistical analysis. C, E and F/G were 15.5 mm ± 1.3, 99.8 mm ± 4.3 and 1.63 ± 10, respectively. F/G, H/I, and H/J were larger in male (ρ < .01). All data of the pons showed no statistically significant differences among age groups. E of the seventh decades was shorter than that of the third decades (ρ < .05). C(12.7 mm ± 1.4) in OPCD and F/G(1.81 ± .10) in Wallerian degeneration (± < .01) showed the most significant differences when they were compared to the normal. Although the cerebellum decreased in size with age, the pons maintained its size up to eighth decades. The measurement of middle cerebellar peduncle on axial plane (C) and the ratio of basis pontis on midsagittal plane (F/G) were important in the evaluation of OPCD and Wallerian degeneration, respectively

  20. Evaluation of oxidative stress status and antioxidant capacity in patients with renal cell carcinoma

    OpenAIRE

    Aldemir, Mustafa; Karaguzel, Ersagun; Okulu, Emrah; Gudeloglu, Ahmet; Ener, Kemal; Ozayar, Asim; Erel, Ozcan

    2015-01-01

    Introduction We evaluated and compared the serum oxidative stress and antioxidant enzymes in patients with renal cell carcinoma (RCC) and the control group. Material and methods The prospective study consisted of 97 patients with RCC (Group 1) and 80 age and sex matched healthy volunteers (Group 2). Group 1 and 2 were compared concerning serum mean total oxidant status (TOS), total antioxidant capacity (TAC), paraoxonase-1 (PON-1), arylesterase, total thiol, catalase (CAT), myeloperoxidase (M...

  1. Ocular distribution of antioxidant enzyme paraoxonase & its alteration in cataractous lens & diabetic retina

    Directory of Open Access Journals (Sweden)

    Subramaniam Rajesh Bharathidevi

    2017-01-01

    Interpretation & conclusions: Distribution of PON enzyme and its activity in ocular tissues is reported here. The study revealed maximal PON activity in lens and retina, which are prone to higher oxidative stress. Differential activities of PON were observed in the lens and retinal tissues from cataractous and diabetic patients, respectively.

  2. A Novel Line Coding Pair for Fully Passive Long Reach {WDM-PON}s

    DEFF Research Database (Denmark)

    Presi, Marco; Proietti, Roberto; Prince, Kamau

    2008-01-01

    A novel line coding pair allows to use unsaturated flective-SOAs as upstream remodulator in long-reach WDM-PONs. Full-duplex and symmetric 80 km reach is demonstrated without in-line amplification at 1.25 Gb/s......A novel line coding pair allows to use unsaturated flective-SOAs as upstream remodulator in long-reach WDM-PONs. Full-duplex and symmetric 80 km reach is demonstrated without in-line amplification at 1.25 Gb/s...

  3. Biomarkers of Sensitivity and Exposure in Washington State Pesticide Handlers

    Science.gov (United States)

    Keifer, M.C.; Checkoway, H.; De Roos, A.J.; Farin, F.M.; Fenske, R.A.; Richter, R.J.; van Belle, G.; Furlong, C.E.

    2011-01-01

    Organophosphate (OP) and N-methyl-carbamate (CB) insecticides are widely used in agriculture in the US and abroad. These compounds – which inhibit acetylcholinesterase (AChE) enzyme activity – continue to be responsible for a high proportion of pesticide poisonings among US agricultural workers. It is possible that some individuals may be especially susceptible to health effects related to OP/CB exposure. The paraoxonase (PON1) enzyme metabolizes the highly toxic oxon forms of some OPs, and an individual's PON1 status may be an important determinant of his or her sensitivity to these chemicals. This chapter discusses methods used to characterize individual PON1 status and reviews previous epidemiologic studies that have evaluated PON1-related sensitivity to OPs in relation to various health endpoints. It also describes an ongoing longitudinal study among OP-exposed agricultural pesticide handlers who are participating in a recently implemented cholinesterase monitoring program in Washington State. This study will evaluate handlers' PON1 status as a hypothesized determinant of butyrylcholinesterase (BuChE) inhibition. Such studies will be useful to determine how regulatory risk assessments might account for differences in PON1-related OP sensitivity when characterizing inter-individual variability in risk related to OP exposure. Recent work assessing newer and more sensitive biomarkers of OP exposure is also discussed briefly in this chapter. PMID:20221867

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

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... Objectives: In this study, we aimed to investigate serum PON1 activity and lipid hydroperoxide (LOOH) levels in adult football players after three days ... oxidative stress after three days football tournament. In addition, physical activity for a ... polymorphism, gender, and exercise. Furthermore, it has been ...

  5. Paraoxonase 1 gene (Gln192–Arg polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Mohamed Fahmy Elnoamany

    2012-06-01

    Conclusion: Arg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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. Grant management procedure for energy saving TDM-PONs

    Science.gov (United States)

    Alaelddin, Fuad Yousif Mohammed; Newaz, S. H. Shah; AL-Hazemi, Fawaz; Choi, Jun Kyun

    2018-01-01

    In order to minimize energy consumption in Time Division Multiplexing-Passive Optical Network (TDM-PON), IEEE and ITU-T have mandated sleep mode mechanism for Optical Network Units (ONUs) in the latest TDM-PON standards (e.g. IEEE P1904.1 SIEPON, ITU-T G.sup45). The sleep mode mechanism is a promising mean for maximizing energy saving in an ONU. An ONU in sleep mode flips between sleep and active state depending on the presence or absent of upstream and downstream frames. To ensure Quality of Service (QoS) of upstream frames, the recent TDM-PON standards introduced an early wake-up mechanism, in which an ONU is forced to leave the sleep state on upstream frame arrival. When the Optical Line Terminal (OLT) of a TDM-PON allows early wake-up of its connected ONUs, it allocates gratuitous grants for the sleeping ONUs along with allocating upstream grants for the ONUs in active state. Note that, the gratuitous grants control message sent periodically by the OLT on Inter-Gratuitous grant Interval (IGI) time. After leaving sleep state due to the arrival of upstream frame, the ONU uses its allocated gratuitous grant to send a control message mentioning the amount of upstream bandwidth (upstream grant) required in order to forward the remaining frames in its buffer. However, the existing early wake-up process of ONU can lead to increase the energy consumption of an ONU. It is because of the ONU wakes-up immediately from the sleep state on arrival of the upstream frame, but even so, it needs to wait for forwarding the frame until its allocated gratuitous grant period, resulting in spending energy unnecessarily. In addition, current energy saving solution for TDM-PONs do not provide a clear solution on how to manage different types of grants (e.g. listening grant, upstream transmission grant) within a Dynamic Bandwidth Allocation (DBA) polling cycle. To address this problem, we propose a state-of-art Grant Management Procedure (GMP) in order to maximize energy saving in a TDM-PON

  9. CYP2C19 and PON1 polymorphisms regulating clopidogrel bioactivation in Chinese, Malay and Indian subjects.

    Science.gov (United States)

    Chan, Mark Y; Tan, Karen; Tan, Huay-Cheem; Huan, Pei-Tee; Li, Bei; Phua, Qian-Hui; Lee, Hong-Kai; Lee, Chi-Hang; Low, Adrian; Becker, Richard C; Ong, Wen-Chong; Richards, Mark A; Salim, Agus; Tai, E-Shyong; Koay, Evelyn

    2012-04-01

    AIM, MATERIALS & METHODS: We investigated the functional significance of CYP2C19*2, *3, *17 and PON1 Q192R SNPs in 89 consecutive Asian patients on clopidogrel treatment and the prevalence of functionally significant polymorphisms among 300 Chinese, Malays and Asian Indians. Both CYP2C19 loss-of-function alleles (*2 or *3) were associated with higher platelet reactivity while the CYP2C19 gain-of-function allele (*17) had lower platelet reactivity. For PON1, the median PRI was not significantly different between the QQ, QR and RR groups. The allele frequencies of CYP2C19*2, CYP2C19*3 and CYP2C19*17 were 0.280, 0.065 and 0.010 (rare) for Chinese, 0.310, 0.050 and 0.025 for Malays, and 0.375, 0.010 (rare) and 0.165 for Indians, respectively. Our data suggest that genotyping studies to investigate clopidogrel response should include CYP2C19*2 and *3 but not *17 polymorphisms in Chinese, and CYP2C19*2 and *17 polymorphisms but not *3 in Indians. All three polymorphisms should preferably be genotyped in Malays.

  10. Modelisation et simulation d'un PON (Passive Optical Network) base ...

    African Journals Online (AJOL)

    English Title: Modeling and simulation of a PON (Passive Optical Network) Based on hybrid technology WDM/TDM. English Abstract. This development is part of dynamism of design for a model combining WDM and TDM multiplexing in the optical network of PON (Passive Optical Network) type, in order to satisfy the high bit ...

  11. Effect of the Oxidant-Antioxidant System in Seminal Plasma on Varicocele and Idiopathic Infertility in Male Humans.

    Science.gov (United States)

    Yazar, Hayrullah; Halis, Fikret; Nasir, Yasemin; Guzel, Derya; Akdogan, Mehmet; Gokce, Ahmet

    2017-05-01

    The aim of this study was to investigate seminal oxidant-antioxidant activity in idiopathic and varicocele infertility in men. Total anti-oxidant capacity (TAC), total oxidant status (TOS), paraoxonase (PON1), aryl esterase (ARE), and total thiol levels (TTL) were measured in seminal plasma with an autoanalyzer. The TOS/TAC ratio was determined as the oxidative stress index (OSI). A histopathological evaluation of the sperm was performed in the andrology laboratory of the hospital. Number, motility, morphology, volume, pH, and leukocytes were evaluated in all samples according to World Health Organization criteria. The three study groups were as follows: G1, males with idiopathic infertility; G2, males with varicocele infertility; and G3, normal healthy males (had fathered a child in the last 2 years). Each group was composed of 36 men (age, 25 - 40 years). The Rel Assay Diagnostics kit was used to determine the levels of the parameters. The study was conducted according to the principles of the declaration of Helsinki and was approved by Sakarya University Medicine Faculty Ethic Committee (e.n: 16214662/050.01.04/07). Statistical significance was assumed if p 0.05). The ARE was not performed in group 3 (control) due to a methodological problem. PON1 levels in infertile subjects were significantly higher than those of fertile subjects.

  12. The application of cost-effective lasers in coherent UDWDM-OFDM-PON aided by effective phase noise suppression methods.

    Science.gov (United States)

    Liu, Yue; Yang, Chuanchuan; Yang, Feng; Li, Hongbin

    2014-03-24

    Digital coherent passive optical network (PON), especially the coherent orthogonal frequency division multiplexing PON (OFDM-PON), is a strong candidate for the 2nd-stage-next-generation PON (NG-PON2). As is known, OFDM is very sensitive to the laser phase noise which severely limits the application of the cost-effective distributed feedback (DFB) lasers and more energy-efficient vertical cavity surface emitting lasers (VCSEL) in the coherent OFDM-PON. The current long-reach coherent OFDM-PON experiments always choose the expensive external cavity laser (ECL) as the optical source for its narrow linewidth (usuallyOFDM-PON and study the possibility of the application of the DFB lasers and VCSEL in coherent OFDM-PON. A typical long-reach coherent ultra dense wavelength division multiplexing (UDWDM) OFDM-PON has been set up. The numerical results prove that the OBE method can stand severe phase noise of the lasers in this architecture and the DFB lasers as well as VCSEL can be used in coherent OFDM-PON. In this paper, we have also analyzed the performance of the RF-pilot-aided (RFP) phase noise suppression method in coherent OFDM-PON.

  13. A TTC upgrade proposal using bidirectional 10G-PON FTTH technology

    Science.gov (United States)

    Kolotouros, D. M.; Baron, S.; Soos, C.; Vasey, F.

    2015-04-01

    A new generation FPGA-based Timing-Trigger and Control (TTC) system based on emerging Passive Optical Network (PON) technology is being proposed to replace the existing off-detector TTC system used by the LHC experiments. High split ratio, dynamic software partitioning, low and deterministic latency, as well as low jitter are required. Exploiting the latest available technologies allows delivering higher capacity together with bidirectionality, a feature absent from the legacy TTC system. This article focuses on the features and capabilities of the latest TTC-PON prototype based on 10G-PON FTTH components along with some metrics characterizing its performance.

  14. A TTC upgrade proposal using bidirectional 10G-PON FTTH technology

    International Nuclear Information System (INIS)

    Kolotouros, D.M.; Baron, S.; Soos, C.; Vasey, F.

    2015-01-01

    A new generation FPGA-based Timing-Trigger and Control (TTC) system based on emerging Passive Optical Network (PON) technology is being proposed to replace the existing off-detector TTC system used by the LHC experiments. High split ratio, dynamic software partitioning, low and deterministic latency, as well as low jitter are required. Exploiting the latest available technologies allows delivering higher capacity together with bidirectionality, a feature absent from the legacy TTC system. This article focuses on the features and capabilities of the latest TTC-PON prototype based on 10G-PON FTTH components along with some metrics characterizing its performance

  15. Neuro-protective effect of rutin against Cisplatin-induced neurotoxic rat model.

    Science.gov (United States)

    Almutairi, Mashal M; Alanazi, Wael A; Alshammari, Musaad A; Alotaibi, Moureq Rashed; Alhoshani, Ali R; Al-Rejaie, Salim Salah; Hafez, Mohamed M; Al-Shabanah, Othman A

    2017-09-29

    Cisplatin is widely used chemotherapeutic agent for cancer treatment with limited uses due to its neurotoxic side effect. The aim of this study was to determine the potential preventive effects of rutin on the brain of cisplatin- neurotoxic rat model. Forty rats were divided into four groups. Group-1 (control group) was intra-peritoneal (IP) injected with 2.5 ml/kg saline. Group-2 (rutin group) was orally administrated 30 mg/kg rutin dissolved in water for 14 days. Group-3 (cisplatin group) was IP received 5 mg/kg cisplatin single dose. Group-4 (rutin and cisplatin group) was orally administrated 30 mg/kg rutin dissolved in water for 14 days with a single dose of 5 mg/kg cisplatin IP on day ten. Brain tissues from frontal cortex was used to extract RNA, the gene expression levels of paraoxonase-1 (PON-1), PON-2, PON-3, peroxisome proliferator-activated receptor delta (PPAR-δ), and glutathione peroxidase (GPx) was investigated by Real-time PCR. Cisplatin significantly decreased the expression levels of PON-1, PON-3, PPAR-δ and GPX whereas significantly increased PON-2 expression levels. Co-administration of Rutin prevented the cisplatin-induced toxicity by restoring the alteration in the studied genes to normal values as in the control group. This study showed that Rutin has neuroprotective effect and reduces cisplatin- neurotoxicity with possible mechanism via the antioxidant pathway.

  16. OFDM RF power-fading circumvention for long-reach WDM-PON.

    Science.gov (United States)

    Chow, C W; Yeh, C H; Sung, J Y

    2014-10-06

    We propose and demonstrate an orthogonal frequency division multiplexing (OFDM) radio-frequency (RF) power-fading circumvention scheme for long-reach wavelength-division-multiplexed passive-optical-network (LR-WDM-PON); hence the same capacity of 40 Gb/s can be provided to all the optical-networking-units (ONUs) in the LR-WDM-PON. Numerical analysis and proof-of-concept experiment are performed.

  17. A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS

    NARCIS (Netherlands)

    Wills, A-M.; Cronin, S.; Slowik, A.; Kasperaviciute, D.; Van Es, M. A.; Morahan, J. M.; Valdmanis, P. N.; Meininger, V.; Melki, J.; Shaw, C. E.; Rouleau, G. A.; Fisher, E. M. C.; Shaw, P. J.; Morrison, K. E.; Pamphlett, R.; Van den Berg, L. H.; Figlewicz, D. A.; Andersen, P. M.; Al-Chalabi, A.; Hardiman, O.; Purcell, S.; Landers, J. E.; Brown, R. H.

    2009-01-01

    Background: Six candidate gene studies report a genetic association of DNA variants within the paraoxonase locus with sporadic amyotrophic lateral sclerosis (ALS). However, several other large studies, including five genome-wide association studies, have not duplicated this finding. Methods: We

  18. The 40 Gbps cascaded bit-interleaving PON

    Science.gov (United States)

    Vyncke, A.; Torfs, G.; Van Praet, C.; Verbeke, M.; Duque, A.; Suvakovic, D.; Chow, H. K.; Yin, X.

    2015-12-01

    In this paper, a 40 Gbps cascaded bit-interleaving passive optical network (CBI-PON) is proposed to achieve power reduction in the network. The massive number of devices in the access network makes that power consumption reduction in this part of the network has a major impact on the total network power consumption. Starting from the proven BiPON technology, an extension to this concept is proposed to introduce multiple levels of bit-interleaving. The paper discusses the CBI protocol in detail, as well as an ASIC implementation of the required custom CBI Repeater and End-ONT. From the measurements of this first 40 Gbps ASIC prototype, power consumption reduction estimates are presented.

  19. A CLS-based survivable and energy-saving WDM-PON architecture

    Science.gov (United States)

    Zhu, Min; Zhong, Wen-De; Zhang, Zhenrong; Luan, Feng

    2013-11-01

    We propose and demonstrate an improved survivable and energy-saving WDM-PON with colorless ONUs. It incorporates both energy-saving and self-healing operations. A simple effective energy-saving scheme is proposed by including an energy-saving control unit in the OLT and a control unit at each ONU. The energy-saving scheme realizes both dozing and sleep (offline) modes, which greatly improves the energy-saving efficiency for WDM-PONs. An intelligent protection switching scheme is designed in the OLT, which can distinguish if an ONU is in dozing/sleep (offline) state or a fiber is faulty. Moreover, by monitoring the optical power of each channel on both working and protection paths, the OLT can know the connection status of every fiber path, thus facilitating an effective protection switching and a faster failure recovery. The improved WDM-PON architecture not only significantly reduces energy consumption, but also performs self-healing operation in practical operation scenarios. The scheme feasibility is experimentally verified with 10 Gbit/s downstream and 1.25 Gbit/s upstream transmissions. We also examine the energy-saving efficiency of our proposed energy-saving scheme by simulation, which reveals that energy saving mainly arises from the dozing mode, not from the sleep mode when the ONU is in the online state.

  20. Energy-efficient optical network units for OFDM PON based on time-domain interleaved OFDM technique.

    Science.gov (United States)

    Hu, Xiaofeng; Cao, Pan; Zhang, Liang; Jiang, Lipeng; Su, Yikai

    2014-06-02

    We propose and experimentally demonstrate a new scheme to reduce the energy consumption of optical network units (ONUs) in orthogonal frequency division multiplexing passive optical networks (OFDM PONs) by using time-domain interleaved OFDM (TI-OFDM) technique. In a conventional OFDM PON, each ONU has to process the complete downstream broadcast OFDM signal with a high sampling rate and a large FFT size to retrieve its required data, even if it employs a portion of OFDM subcarriers. However, in our scheme, the ONU only needs to sample and process one data group from the downlink TI-OFDM signal, effectively reducing the sampling rate and the FFT size of the ONU. Thus, the energy efficiency of ONUs in OFDM PONs can be greatly improved. A proof-of-concept experiment is conducted to verify the feasibility of the proposed scheme. Compared to the conventional OFDM PON, our proposal can save 17.1% and 26.7% energy consumption of ONUs by halving and quartering the sampling rate and the FFT size of ONUs with the use of the TI-OFDM technology.

  1. 128 Gb/s TWDM PON system using dispersion-supported transmission method

    Science.gov (United States)

    Bindhaiq, Salem; Zulkifli, Nadiatulhuda; Supa'at, Abusahmah M.; Idrus, Sevia M.; Salleh, M. S.

    2017-11-01

    Time and wavelength division multiplexed passive optical network (TWDM-PON) trend is considered as the most extraordinary trend of the next generation solution to accommodate exponential traffic growth for converged new services. In this paper, we briefly review recent progress on TWDM-PON system through the use of low cost directly modulated lasers (DMLs) transmission for various line rate transmissions to date. Furthermore, through simulation, we propose and evaluate a cost effective way to upgrade TWDM-PON up to a symmetric capacity of 128 Gb/s using fiber Bragg gratings (FBGs) in optical line terminal (OLT) as a paramount dispersion manager in high speed light-wave systems in both upstream and downstream directions. A low cost and potential chirpless directed modulated grating laser (DMGL) is employed for downstream link and DML with a single delay-interferometer (DI) is employed for upstream link. After illustrating the demonstrated system architecture and configuration, we present the results and analysis to prove the system feasibility. The results show that a successful transmission is achieved over 40 km single mode fiber with a power budget of 33.7 dB, which could support 1:256 splitting ratio.

  2. Dynamic Bandwidth Allocation with Effective Utilization of Polling Interval over WDM/TDM PON

    Science.gov (United States)

    Ni, Cuiping; Gan, Chaoqin; Gao, Ziyue

    2014-12-01

    WDM/TDM (wavelength-division multiplexing/time-division multiplexing) PON (passive optical network) appears to be an attractive solution for the next generation optical access networks. Dynamic bandwidth allocation (DBA) plays a crucial role in efficiently and fairly allocating the bandwidth among all users in WDM/TDM PON. In this paper, two dynamic bandwidth allocation schemes (DBA1 and DBA2) are proposed to eliminate the idle time of polling cycles (i.e. polling interval), improve bandwidth utilization and make full use of bandwidth resources. The two DBA schemes adjust the time slot of sending request information and make fair scheduling among users to achieve the effective utilization of polling interval in WDM/TDM PON. The simulation and theoretical analyses verify that the proposed schemes outperform the conventional DBA scheme. We also make comparisons between the two schemes in terms of bandwidth utilization and average packet delay to further demonstrate the effectiveness of the scheme of DBA2.

  3. Coherent Detection for 1550 nm, 5 Gbit/s VCSEL Based 40 km Bidirectional PON Transmission

    DEFF Research Database (Denmark)

    Jensen, Jesper Bevensee; Rodes Lopez, Roberto; Zibar, Darko

    2011-01-01

    Coherent detection of directly modulated 1550nm VCSELs in 5Gbit/s bidirectional 40km SSMF PON-links is presented. Receiver sensitivity of –37.3dBm after transmission is achieved with 30dB system margin, corresponding to 1:1024 passive powersplitting.......Coherent detection of directly modulated 1550nm VCSELs in 5Gbit/s bidirectional 40km SSMF PON-links is presented. Receiver sensitivity of –37.3dBm after transmission is achieved with 30dB system margin, corresponding to 1:1024 passive powersplitting....

  4. Remotely controllable WDM-PON technology for wireless fronthaul/backhaul application

    DEFF Research Database (Denmark)

    Eiselt, Michael H.; Wagner, Christoph; Lawin, Mirko

    2016-01-01

    Low-cost WDM-PON solutions for fronthaul and backhaul applications will include remotely controlled tail-end transceivers. We report on control aspects of these transceivers and how standardization is evolving to enable these applications.......Low-cost WDM-PON solutions for fronthaul and backhaul applications will include remotely controlled tail-end transceivers. We report on control aspects of these transceivers and how standardization is evolving to enable these applications....

  5. Can target-to-pons ratio be used as a reliable method for the analysis of [11C]PIB brain scans?

    Science.gov (United States)

    Edison, P; Hinz, R; Ramlackhansingh, A; Thomas, J; Gelosa, G; Archer, H A; Turkheimer, F E; Brooks, D J

    2012-04-15

    (11)C]PIB is the most widely used PET imaging marker for amyloid in dementia studies. In the majority of studies the cerebellum has been used as a reference region. However, cerebellar amyloid may be present in genetic Alzheimer's (AD), cerebral amyloid angiopathy and prion diseases. Therefore, we investigated whether the pons could be used as an alternative reference region for the analysis of [(11)C]PIB binding in AD. The aims of the study were to: 1) Evaluate the pons as a reference region using arterial plasma input function and Logan graphical analysis of binding. 2) Assess the power of target-to-pons ratios to discriminate controls from AD subjects. 3) Determine the test-retest reliability in AD subjects. 4) Demonstrate the application of target-to-pons ratio in subjects with elevated cerebellar [(11)C]PIB binding. 12 sporadic AD subjects aged 65 ± 4.5 yrs with a mean MMSE 21.4 ± 4 and 10 age-matched control subjects had [(11)C]PIB PET with arterial blood sampling. Three additional subjects (two subjects with pre-symptomatic presenilin-1 mutation carriers and one probable familial AD) were also studied. Object maps were created by segmenting individual MRIs and spatially transforming the gray matter images into standard stereotaxic MNI space and then superimposing a probabilistic atlas. Cortical [(11)C]PIB binding was assessed with an ROI (region of interest) analysis. Parametric maps of the volume of distribution (V(T)) were generated with Logan analysis. Additionally, parametric maps of the 60-90 min target-to-cerebellar ratio (RATIO(CER)) and the 60-90 min target-to-pons ratio (RATIO(PONS)) were computed. All three approaches were able to differentiate AD from controls (p0.83); RATIO(CER) performed best closely followed by RATIO(PONS). The two subjects with presenilin-1 mutations and the probable familial AD case showed no significant differences in cortical binding using RATIO(CER), but the RATIO(PONS) approach revealed higher [(11)C]PIB binding in

  6. PON-Sol: prediction of effects of amino acid substitutions on protein solubility.

    Science.gov (United States)

    Yang, Yang; Niroula, Abhishek; Shen, Bairong; Vihinen, Mauno

    2016-07-01

    Solubility is one of the fundamental protein properties. It is of great interest because of its relevance to protein expression. Reduced solubility and protein aggregation are also associated with many diseases. We collected from literature the largest experimentally verified solubility affecting amino acid substitution (AAS) dataset and used it to train a predictor called PON-Sol. The predictor can distinguish both solubility decreasing and increasing variants from those not affecting solubility. PON-Sol has normalized correct prediction ratio of 0.491 on cross-validation and 0.432 for independent test set. The performance of the method was compared both to solubility and aggregation predictors and found to be superior. PON-Sol can be used for the prediction of effects of disease-related substitutions, effects on heterologous recombinant protein expression and enhanced crystallizability. One application is to investigate effects of all possible AASs in a protein to aid protein engineering. PON-Sol is freely available at http://structure.bmc.lu.se/PON-Sol The training and test data are available at http://structure.bmc.lu.se/VariBench/ponsol.php mauno.vihinen@med.lu.se Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Investigation of interfacial resistance between LiCoO{sub 2} cathode and LiPON electrolyte in the thin film battery

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Eunkyung; Hong, Chan; Tak, Yongsug [Department of Chemical Engineering, Inha University, Inchon 402-751 (Korea, Republic of); Nam, Sang Cheol [Nuricell Inc., Jungrang-Ku, Seoul 131-220 (Korea, Republic of); Cho, Sungbaek [Agency for Defense Development, P.O. Box 35, Daejeon (Korea, Republic of)

    2006-09-13

    All solid-state thin film battery was prepared with conventional sputtering technologies. Low conductivity of lithium phosphorus oxynitride (LiPON) electrolyte and higher resistance at the interface of LiCoO{sub 2}/LiPON was crucial for the development of thin film battery. Presence of thermally treated Al{sub 2}O{sub 3} thin film at the interface of LiCoO{sub 2}/LiPON decreased the interfacial resistance and increased the discharge capacity with the better cycling behaviors. Surface analysis and electrochemical impedance measurement indicate the formation of solid solution LiCo{sub 1-y}Al{sub y}O{sub 2} at the interface of LiCoO{sub 2}/LiPON. (author)

  8. The metropolitan VoD system based on ethernet/SCM PON

    Science.gov (United States)

    Ji, Wei; Yang, Hongliang; Feng, Dejun; Liu, Yang; Sun, Jande

    2008-11-01

    VoD is a very attractive service which used for entertainment, education and other purposes. In this paper, we present an evolution method that integrates the EPON and SCM-PON by WDM technology to provide high dedicated bandwidth for the metropolitan VoD services. Using DVB, IPTV protocol, unicasting and broadcasting method to maximize the system throughput and by numerical analysis, the hybrid PON system can implement the metropolitan VoD services.

  9. International Conference: Paraoxonases - Basic and Clinical Directions of Current Research (1st) Held in Ann Arbor, Michigan on April 22-24, 2004

    Science.gov (United States)

    2005-04-01

    studies include lipoprotein- and cell-associated flavonoids (from pomegranate, red wine, ginger and licorice), vitamin E, carotenoids (such as 13...7.4, 150 mM NaCl and 37°C with a relatively low concentration of diazoxon as substrate (50 gM) and HPLC detection of the product, pyrimidinol. PON1

  10. Intra and Inter-PON ONU to ONU Virtual Private Networking using OFDMA in a Ring Topology

    DEFF Research Database (Denmark)

    Deng, Lei; Zhao, Ying; Pang, Xiaodan

    2011-01-01

    Abstract—In this paper, we propose a novel WDM-PON architecture to support efficient and bandwidth-scalable virtual private network (VPN) emulation over both inter-PON and intra- PON. The virtual ring link for the VPN communications among ONUs is realized by using additionally low-cost optical pa...

  11. The tectopontine projection the the rat with comments on visual pathways to the basilar pons

    International Nuclear Information System (INIS)

    Burne, R.A.; Azizi, S.A.; Mihailoff, G.A.; Woodward, D.J.

    1981-01-01

    The projection from the superior and inferior colliculi to the basilar pons in the rat was studied with the technique of orthograde transport of labeled amino acids and autoradiography. Injections restricted to the medial or lateral regions of the superior colliculus gave rise to grain labeling representing terminal fields over the ipsilateral peduncular, dorsolateral, and ventrolateral regions of the caudal basilar pons and over the dorsomedial area of the contralateral nucleus reticularis tegmenti pontis (NRTP). The pontine projection from the superior colliculus to the lateral basilar pons is topographically organized; the medial superior colliculus projects primarily to the peduncular region, whereas the lateral superior colliculus terminates chiefly in ventrolateral pontine areas. A projection from the superior colliculus to the contralateral dorsomedial pontine and medial peduncular pontine regions, a previously undescribed finding, has also been shown. Descending fibers from the inferior colliculus do not appear to terminate extensively within the basilar pons but rather course adjacent to pontine cells of the dorsolateral region in the caudal pons. Pretectal nuclei project ipsilaterally to medial and lateral nuclei in the rostral and middle basilar pons, respectively. A rostrocaudal topography exists in the tectopontine projection; the pretectum projects to rostromiddle basilar pons, the superior colliculus to more caudal pontine regions, and the inferior colliculus (although sparsely) to further caudal areas. The pontine projection pattern from the colliculi and pretectum differs from the pontine afferents from the visual cortices

  12. Highly Reliable PON Optical Splitters for Optical Access Networks in Outside Environments

    Science.gov (United States)

    Watanabe, Hiroshi; Araki, Noriyuki; Fujimoto, Hisashi

    Broadband optical access services are spreading throughout the world, and the number of fiber to the home (FTTH) subscribers is increasing rapidly. Telecom operators are constructing passive optical networks (PONs) to provide optical access services. Externally installed optical splitters for PONs are very important passive devices in optical access networks, and they must provide satisfactory performance as outdoor plant over long periods. Therefore, we calculate the failure rate of optical access networks and assign a failure rate to the optical splitters in optical access networks. The maximum cumulative failure rate of 1 × 8 optical splitters was calculated as 0.025 for an optical access fiber length of 2.1km and a 20-year operating lifetime. We examined planar lightwave circuit (PLC) type optical splitters for use as outside plant in terms of their optical characteristics and environmental reliability. We confirmed that PLC type optical splitters have sufficient optical performance for a PON splitter and sufficient reliability as outside plant in accordance with ITU-T standard values. We estimated the lifetimes of three kinds of PLC type optical splitters by using accelerated aging tests. The estimated failure rate of these splitters installed in optical access networks was below the target value for the cumulative failure rate, and we confirmed that they have sufficient reliability to maintain the quality of the network service. We developed 1 × 8 optical splitter modules with plug and socket type optical connectors and optical fiber cords for optical aerial closures designed for use as outside plant. These technologies make it easy to install optical splitters in an aerial optical closure. The optical splitter modules have sufficient optical performance levels for PONs because the insertion loss at the commercially used wavelengths of 1.31 and 1.55µm is less than the criterion established by ITU-T Recommendation G.671 for optical splitters. We performed a

  13. [High-density lipoproteins (HDL) size and composition are modified in the rat by a diet supplemented with "Hass" avocado (Persea americana Miller)].

    Science.gov (United States)

    Pérez Méndez, Oscar; García Hernández, Lizbeth

    2007-01-01

    To determine the effects of dietary avocado on HDL structure and their associated enzyme, paraoxonase 1 (PON1). Fifteen Wistar male rats received avocado as part of their daily meal (5 g by 17.5 g chow diet), keeping the caloric intake similar to the control group (n=15) that received their usual chow diet. After 5 weeks, HDL were isolated by sequential ultracentrifugation and their size and chemical composition were analyzed. PON1 was determined in serum spectrophotometrically using phenylacetate as substrate. Rats that received avocado had about 27% lower triglycerides plasma levels whereas their HDL-cholesterol was 17% higher as compared to control group. The mean HDL Stokes diameter was significantly lower in avocado group (11.71 +/- 0.8 vs. 12.27 +/- 0.26 nm, in control group, p avocado group. HDL structural modifications induced by avocado were not related to modifications of LCAT and PLTP activities, but occurred in parallel with higher serum levels of PON1 activity when compared to the controls (57.4 +/- 8.9 vs. 43.0 +/- 5.6 micromol/min/mL serum, p avocado in the diet decreased plasma triglycerides, increased HDL-cholesterol plasma levels and modified HDL structure. The latter effect may enhance the antiatherogenic properties of HDL since PON1 activity also increased as a consequence of avocado.

  14. In silico Analysis of the Functional and Structural Impacts of Non-synonymous Single Nucleotide Polymorphisms in the Human Paraxonase 1 Gene

    Directory of Open Access Journals (Sweden)

    Sudip Paul

    2015-09-01

    Full Text Available Computational approaches could help in identifying deleterious non-synonymous single nucleotide polymorphisms (nsSNPs in a disease related gene which is a difficult and laborious task through laboratory experiments. In the present study, we analyzed the impacts of nsSNPs on structure and function of Paraxonase 1 (PON1 using different bioinformatics tools. The human PON1 protein sequence and its corresponding gene's SNP information were collected from UniProt and dbSNP databases, respectively. We utilized SIFT, Polyphen, I-Mutant 2.0, MutPred, SNP and GO, PhD-SNP and PANTHER tools in order to examine the total 39 nsSNPs occurring in the PON1 coding region. We filtered the most pathological mutations by combining the scores of the aforementioned servers and found 8 SNPs (G344C, S302L, W281C, D279Y, H134R, F120S, L90P, C42R as deleterious and disease causing. The PDB structure of PON1 protein was obtained from RCSB Protein Data Bank (PDB ID: 1V04. The deleterious SNPs in native PON1 were introduced using Swiss-PDB Viewer package and changes in free energy were observed for six out of eight mutant structures. Two SNPs, S302L (substitution of serine to leucine at 302 position in amino acid sequence and L90P (substitution of leucine to proline at 90 position in amino acid sequence caused the highest energy increase amongst all. The findings implicate that these nsSNPs would be analyzed further in detail to enumerate their possible association with the protein deteriorating and disease causal potentialities.

  15. 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

    Directory of Open Access Journals (Sweden)

    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.

  16. Energy-Saving Mechanism in WDM/TDM-PON Based on Upstream Network Traffic

    Directory of Open Access Journals (Sweden)

    Paola Garfias

    2014-08-01

    Full Text Available One of the main challenges of Passive Optical Networks (PONs is the resource (bandwidth and wavelength management. Since it has been shown that access networks consume a significant part of the overall energy of the telecom networks, the resource management schemes should also consider energy minimization strategies. To sustain the increased bandwidth demand of emerging applications in the access section of the network, it is expected that next generation optical access networks will adopt the wavelength division/time division multiplexing (WDM/TDM technique to increase PONs capacity. Compared with traditional PONs, the architecture of a WDM/TDM-PON requires more transceivers/receivers, hence they are expected to consume more energy. In this paper, we focus on the energy minimization in WDM/TDM-PONs and we propose an energy-efficient Dynamic Bandwidth and Wavelength Allocation mechanism whose objective is to turn off, whenever possible, the unnecessary upstream traffic receivers at the Optical Line Terminal (OLT. We evaluate our mechanism in different scenarios and show that the proper use of upstream channels leads to relevant energy savings. Our proposed energy-saving mechanism is able to save energy at the OLT while maintaining the introduced penalties in terms of packet delay and cycle time within an acceptable range. We might highlight the benefits of our proposal as a mechanism that maximizes the channel utilization. Detailed implementation of the proposed algorithm is presented, and simulation results are reported to quantify energy savings and effects on network performance on different network scenarios.

  17. All-optical virtual private network and ONUs communication in optical OFDM-based PON system.

    Science.gov (United States)

    Zhang, Chongfu; Huang, Jian; Chen, Chen; Qiu, Kun

    2011-11-21

    We propose and demonstrate a novel scheme, which enables all-optical virtual private network (VPN) and all-optical optical network units (ONUs) inter-communications in optical orthogonal frequency-division multiplexing-based passive optical network (OFDM-PON) system using the subcarrier bands allocation for the first time (to our knowledge). We consider the intra-VPN and inter-VPN communications which correspond to two different cases: VPN communication among ONUs in one group and in different groups. The proposed scheme can provide the enhanced security and a more flexible configuration for VPN users compared to the VPN in WDM-PON or TDM-PON systems. The all-optical VPN and inter-ONU communications at 10-Gbit/s with 16 quadrature amplitude modulation (16 QAM) for the proposed optical OFDM-PON system are demonstrated. These results verify that the proposed scheme is feasible. © 2011 Optical Society of America

  18. Efficient eNB inter-communication scheme in converged mobile and NG-PON2 system

    Science.gov (United States)

    Xiao, Simiao; Sun, Xiao; Zhang, Kaibin

    2016-02-01

    In LTE, a new X2-interface is defined to facilitate direct communication between neighboring eNBs. Since LTE is an all-IP network, the X2-interface traffic currently needs to be routed and transponded in L3 at the edge router by IP addressing. As mobile data increases, it is a promising trend to backhaul mobile services based on PON. In this paper, an effective approach for eNB inter-communication over TWDM-PON is proposed. By associating the IP address of eNB and the MAC address of ONU, the "inter-eNB communication in L3" can be mapped into "inter-ONU communication in L2" and transponded via the protocol of PON at the OLT. Thus, fast and cost-effective eNB inter-communication can be realized based on TWDM-PON within one wavelength channel and between different wavelength channels. The increasing data traffic pressure to the core network can also be alleviated.

  19. Integration of Optically Generated Impulse Radio UWB Signals into Baseband WDM-PON

    DEFF Research Database (Denmark)

    Pham, Tien Thang; Yu, Xianbin; Dittmann, Lars

    2011-01-01

    We propose a compact integration system to simultaneously provide wireline and wireless (baseband and ultra-wide band (UWB)) services to end-users in a WDM-PON. A 1-Gbps UWB signal is optically generated and shares the same wavelength with the baseband signal. Error-free performance was achieved...

  20. FDMA-PON architecture according to the FABULOUS European project

    Science.gov (United States)

    Abrate, Silvio; Gaudino, Roberto; Charbonnier, Benoit

    2013-01-01

    In this paper we wish to introduce the FABULOUS European Project, started on the 1st of October 2012, that proposes a new FDMA-PON architecture adopting Faraday rotation and a R-ONU based on a reflective modulator instead of the conventional reflective SOA, designed on purpose and to be realized in silicon photonics, in order to cope with the target performances set by FSAN and the need of realizing low cost devices for the final user.

  1. High performance sandwich structured Si thin film anodes with LiPON coating

    Science.gov (United States)

    Luo, Xinyi; Lang, Jialiang; Lv, Shasha; Li, Zhengcao

    2018-04-01

    The sandwich structured silicon thin film anodes with lithium phosphorus oxynitride (LiPON) coating are synthesized via the radio frequency magnetron sputtering method, whereas the thicknesses of both layers are in the nanometer range, i.e. between 50 and 200 nm. In this sandwich structure, the separator simultaneously functions as a flexible substrate, while the LiPON layer is regarded as a protective layer. This sandwich structure combines the advantages of flexible substrate, which can help silicon release the compressive stress, and the LiPON coating, which can provide a stable artificial solidelectrolyte interphase (SEI) film on the electrode. As a result, the silicon anodes are protected well, and the cells exhibit high reversible capacity, excellent cycling stability and good rate capability. All the results demonstrate that this sandwich structure can be a promising option for high performance Si thin film lithium ion batteries.

  2. The Escape of Sisyphus or What “Post NG-PON2” Should Do Apart from Neverending Capacity Upgrades

    Directory of Open Access Journals (Sweden)

    Martin Maier

    2014-03-01

    Full Text Available The primary design goal of (revolutionary NG-PON1&2 was the provisioning of an ever increasing capacity to cope with video-dominated traffic and handle the explosion of mobile data traffic by means of offloading. Recently, however, questions on the future of “post NG-PON2” have surfaced whether to shift its research focus to business and operation related aspects and move access technology into a substantially different direction than continued capacity upgrades. In fact, recent studies indicate that ultimately the major factor limiting the performance of 4G mobile networks is latency rather than capacity of the backhaul. In this paper, we review recently proposed low-latency techniques for NG-PONs that require architectural modifications at the remote node or distribution fiber level and highlight advanced network coding and real-time polling based low-latency techniques that can be implemented in software, enable NG-PONs to carry higher traffic loads and thereby extend their lifetime, and maintain the passive nature of existent optical distribution networks. Furthermore, we elaborate on emerging trends and open challenges for future post NG-PON2 research. To better understand their true potential, we put them into a wider non-technical and historical perspective leading up to a sustainable Third Industrial Revolution (TIR economy and its underlying Energy Internet.

  3. Benfotiamine enhances antioxidant defenses and protects against cisplatin-induced DNA damage in nephrotoxic rats.

    Science.gov (United States)

    Harisa, Gamaleldin I

    2013-08-01

    The objective of the present study was to assess superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), paraoxonase (PON1), glutathione reductase (GR), and catalase (CAT) activities ratio and their relationship with DNA oxidative damage in rats treated with cisplatin (3 mg/kg bwt/day) in the presence and absence of benfotiamine (100 mg/kg/day) for 25 days. Cisplatin-induced renal damage was evidenced by renal dysfunction and elevated oxidative stress markers. SOD activity and levels of nitric oxide, protein carbonyl, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine were significantly increased by cisplatin treatment. Moreover, the ratios of GPx/GR, SOD/GPx, SOD/CAT, and SOD/PON1 were significantly increased compared to control. In contrast, glutathione levels were significantly decreased by cisplatin treatment. Simultaneous treatment of rats with cisplatin and benfotiamine ameliorate these variables to values near to those of control rats. This study suggests that benfotiamine can prevent cisplatin-induced nephrotoxicity by inhibiting formation reactive species of oxygen and nitrogen. © 2013 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

    Tinggaard, Jeanette; 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....

  5. N-(3-oxododecanoyl)-l-homoserine lactone modulates mitochondrial function and suppresses proliferation in intestinal goblet cells.

    Science.gov (United States)

    Tao, Shiyu; Niu, Liqiong; Cai, Liuping; Geng, Yali; Hua, Canfeng; Ni, Yingdong; Zhao, Ruqian

    2018-05-15

    The quorum-sensing molecule N‑(3‑oxododecanoyl)‑l‑homoserine lactone (C12-HSL), produced by the Gram negative human pathogenic bacterium Pseudomonas aeruginosa, modulates mammalian cell behavior. Our previous findings suggested that C12-HSL rapidly decreases viability and induces apoptosis in LS174T goblet cells. In this study, the effects of 100 μM C12-HSL on mitochondrial function and cell proliferation in LS174T cells treated for 4 h were evaluated by real-time PCR, enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The results showed that the activities of mitochondrial respiratory chain complexes IV and V were significantly increased (P cells after C12-HSL treatment, with elevated intracellular ATP generation (P cell cycle arrest upon C12-HSL treatment. Apoptosis and cell proliferation related genes showed markedly altered expression levels (P cells after C12-HSL treatment. Moreover, the paraoxonase 2 (PON2) inhibitor TQ416 (1 μM) remarkably reversed the above C12-HSL associated effects in LS174T cells. These findings indicated that C12-HSL alters mitochondrial energy production and function, and inhibits cell proliferation in LS174T cells, with PON2 involvement. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Coronary artery disease and the frequencies of MTHFR and PON1 gene polymorphism studies in a varied population of Hyderabad, Telangana region in south India

    Directory of Open Access Journals (Sweden)

    Kavitha Matam

    2015-04-01

    Full Text Available Coronary artery disease (CAD also known as coronary heart disease is one of the leading causes of death and disability worldwide. Genetic and environmental factors play an important role in the pathogenesis and progression of CAD. The aim of this study was to evaluate the combined contribution of 3 gene polymorphisms to the risk of CAD and gene–gene interaction in the south Indian population. In this case-control study, 200 cases of CAD and 200 healthy controls were recruited. We studied 3 well known genetic polymorphisms of MTHFR (C677T; rs1801133, PON1 (Q192R; rs662 and ACE (I/D: rs4646994 in relation to CAD in South Indian population. Polymerase chain reaction (PCR was carried out and followed by the restriction fragment length polymorphism and agarose gel electrophoresis. Genotypes of MTHFR C677T, CT and CT+TT, and PON1 Q192R QR were associated with the risk of CAD (C677T CT+TT vs CC: odds ratio [OR] = 3.3, 95% confidence intervals [CI] = 1.8–6.2; p = 0.00001, (CT vs CC: OR = 3.2, 95%CI = 1.8–5.6; p = 0.00003, and (Q192R QQ vs QR: OR = 2.1, 95%CI = 1.1–3.9; p = 0.03. The allele frequencies for T vs C: OR = 3.1, 95%CI = 1.8–5.3; p = 0.00001 and R vs Q: OR = 1.3, 95% CI = 1.0–1.7 p = 0.03. Multifactor dimensionality reduction (MDR analysis was carried out with the combination of three genes and the results indicate that MDR analysis showed that, PON1 gene polymorphism formed a significant model in predicting the CAD risk in south Indian population.

  7. Wavelength-agnostic WDM-PON System

    DEFF Research Database (Denmark)

    Wagner, Christoph; Eiselt, Michael; Zou, S.

    2016-01-01

    on the standardization status of this lowcost system in the new ITU-T G.metro draft recommendation, in the context of autonomous tuning. We also discuss some low-effort implementations of the pilot-tone labels and investigate the impact of these labels on the transmission channels.......Next-generation WDM-PON solutions for metro and access systems will take advantage of remotely controlled wavelength-tunable ONUs to keep system costs as low as possible. For such a purpose, each ONU signal can be labeled by a pilot tone modulated onto the optical data stream. We report...

  8. GigaWaM—Next-Generation WDM-PON Enabling Gigabit Per-User Data Bandwidth

    DEFF Research Database (Denmark)

    Prince, Kamau; Gibbon, Timothy Braidwood; Rodes Lopez, Roberto

    2012-01-01

    The “Gigabit access passive optical network using wavelength division multiplexing” project aims to implement 64-Gb/s data transmission over 20-km single-mode fiber. Per-user symmetric data rates of 1-Gb/s will be achieved using wavelength division multiplexing passive optical network (WDM-PON) a...

  9. A Novel Reliable WDM-PON System

    Science.gov (United States)

    Chen, Benyang; Gan, Chaoqin; Qi, Yongqian; Xia, Lei

    2011-12-01

    In this paper, a reliable Wavelength-Division-Multiplexing Passive Optical Network (WDM-PON) system is proposed. It can provide the protection against both the feeder fiber failure and the distribution fiber failure. When the fiber failure occurs, the corresponding switches in the OLT and in the ONU can switch to the protection link without affecting the users in normal status. That is to say, the protection for one ONU is independent of the other ONUs.

  10. Assessment of emerging biomarkers of liver injury in human subjects.

    Science.gov (United States)

    Schomaker, Shelli; Warner, Roscoe; Bock, Jeff; Johnson, Kent; Potter, David; Van Winkle, Joyce; Aubrecht, Jiri

    2013-04-01

    Hepatotoxicity remains a major challenge in drug development. Although alanine aminotransferase (ALT) remains the gold standard biomarker of liver injury, alternative biomarker strategies to better predict the potential for severe drug-induced liver injury (DILI) are essential. In this study, we evaluated the utility of glutamate dehydrogenase (GLDH), purine nucleoside phosphorylase (PNP), malate dehydrogenase (MDH), and paraxonase 1 (PON1) as indicators of liver injury in cohorts of human subjects, including healthy subjects across age and gender, subjects with a variety of liver impairments, and several cases of acetaminophen poisoning. In the healthy subjects, levels of GLDH and MDH were not affected by age or gender. Reference ranges for GLDH and MDH in healthy subjects were 1-10 and 79-176U/L, respectively. In contrast, the levels of PON1 and PNP were not consistent across cohorts of healthy subjects. Furthermore, GLDH and MDH had a strong correlation with elevated ALT levels and possessed a high predictive power for liver injury, as determined by ROC analysis. In contrast, PON1 and PNP did not detect liver injury in our study. Finally, evaluation of patients with acetaminophen-induced liver injury provided evidence that both GLDH and MDH might have utility as biomarkers of DILI in humans. This study is the first to evaluate GLDH, MDH, PON1, and PNP in a large number of human subjects and, and it provides an impetus for prospective clinical studies to fully evaluate the diagnostic value of GLDH and MDH for detection of liver injury.

  11. 10Gbps monolithic silicon FTTH transceiver for PON

    Science.gov (United States)

    Zhang, J.; Liow, T. Y.; Lo, G. Q.; Kwong, D. L.

    2010-05-01

    We propose a new passive optical network (PON) configuration and a novel silicon photonic transceiver architecture for optical network unit (ONU), eliminating the need for an internal laser source in ONU. We adopt dual fiber network configuration. The internal light source in each of the ONUs is eliminated. Instead, an extra seed laser source in the optical line termination (OLT) operates in continuous wave mode to serve the ONUs in the PON as a shared and centralized laser source. λ1 from OLT Tx and λ2 from the seed laser are combined by using a WDM combiner and connected to serve the multiple ONUs through the downstream fibers. The ONUs receive the data in λ1. Meanwhile, the ONUs encode and transmit data in λ2, which are sent back to OLT. The monolithic ONU transceiver contains a wavelength-division-multiplexing (WDM) filter component, a silicon modulator and a Ge photo-detector. The WDM in ONU selectively guides λ1 to the Ge-PD where the data in λ1 are detected and converted to electrical signals, and λ2 to the transmitter where the light is modulated by upstream data. The modulated optical signals in λ2 from ONUs are connected back to OLT through upstream fibers. The monolithic ONU transceiver chip size is only 2mm by 4mm. The crosstalk between the Tx and Rx is measured to be less than -20dB. The transceiver chip is integrated on a SFP+ transceiver board. Both Tx and Rx demonstrated data rate capabilities of up to 10Gbps. By implementing this scheme, the ONU transceiver size can be significantly reduced and the assembly processes will be greatly simplified. The results demonstrate the feasibility of mass manufacturing monolithic silicon ONU transceivers via low cost

  12. Generalized Anxiety Disorder (GAD) and Comorbid Major Depression with GAD Are Characterized by Enhanced Nitro-oxidative Stress, Increased Lipid Peroxidation, and Lowered Lipid-Associated Antioxidant Defenses.

    Science.gov (United States)

    Maes, Michael; Bonifacio, Kamila Landucci; Morelli, Nayara Rampazzo; Vargas, Heber Odebrecht; Moreira, Estefânia Gastaldello; St Stoyanov, Drozdstoy; Barbosa, Décio Sabbatini; Carvalho, André F; Nunes, Sandra Odebrecht Vargas

    2018-05-07

    Accumulating evidence shows that nitro-oxidative pathways play an important role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD) and maybe anxiety disorders. The current study aims to examine superoxide dismutase (SOD1), catalase, lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), malondialdehyde (MDA), glutathione (GSH), paraoxonase 1 (PON1), high-density lipoprotein cholesterol (HDL), and uric acid (UA) in participants with and without generalized anxiety disorder (GAD) co-occurring or not with BD, MDD, or tobacco use disorder. Z unit-weighted composite scores were computed as indices of nitro-oxidative stress driving lipid and protein oxidation. SOD1, LOOH, NOx, and uric acid were significantly higher and HDL and PON1 significantly lower in participants with GAD than in those without GAD. GAD was more adequately predicted by increased SOD + LOOH + NOx and lowered HDL + PON1 composite scores. Composite scores of nitro-oxidative stress coupled with aldehyde and AOPP production were significantly increased in participants with comorbid GAD + MDD as compared with all other study groups, namely MDD, GAD + BD, BD, GAD, and healthy controls. In conclusion, GAD is characterized by increased nitro-oxidative stress and lipid peroxidation and lowered lipid-associated antioxidant defenses, while increased uric acid levels in GAD may protect against aldehyde production and protein oxidation. This study suggests that increased nitro-oxidative stress and especially increased SOD1 activity, NO production, and lipid peroxidation as well as lowered HDL-cholesterol and PON1 activity could be novel drug targets for GAD especially when comorbid with MDD.

  13. Direct-detection optical OFDM superchannel for long-reach PON using pilot regeneration.

    Science.gov (United States)

    Hu, Rong; Yang, Qi; Xiao, Xiao; Gui, Tao; Li, Zhaohui; Luo, Ming; Yu, Shaohua; You, Shanhong

    2013-11-04

    We demonstrate a novel long-reach PON downstream scheme based on the regenerated pilot assisted direct-detection optical orthogonal frequency division multiplexing (DDO-OFDM) superchannel transmission. We use the optical comb source to form DDO-OFDM superchannel, and reserve the center carrier as a seed pilot. The seed pilot is further tracked and reused to generate multiple optical carriers at the local exchange. Each regenerated pilot carrier is selected to beat with an adjacent OFDM sub-band at ONU, so that the electrical bandwidth limitation can be much released compared to the conventional DDO-OFDM superchannel detection. With the proposed proof-of-concept architecture, we experimentally demonstrated a 116.7 Gb/s superchannel OFDM-PON system with transmission reach of 100 km, and 1:64 splitting ratio. We analyze the impact of carrier-to-sideband power ratio (CSPR) on system performance. The experiment result shows that, 5 dB power margin is still remained at ONU using such technique.

  14. 10 Gb/s bidirectional single fibre long reach PON link with distributed Raman amplification

    DEFF Research Database (Denmark)

    Tafur Monroy, Idelfonso; Kjær, Rasmus; Jeppesen, Palle

    2006-01-01

    We report operation of a single fibre bidirectional 80 km long reach PON link with symmetric up- and-downstream data rate of 10 Gb/s supported by distributed Raman fibre amplification only.......We report operation of a single fibre bidirectional 80 km long reach PON link with symmetric up- and-downstream data rate of 10 Gb/s supported by distributed Raman fibre amplification only....

  15. to HDL-cholesterol functionality

    Directory of Open Access Journals (Sweden)

    Malara Marzena

    2016-05-01

    Full Text Available The purpose of this study was to analyse the scientific evidence concerning the effects of two enzymes – paraoxonase 1 and myeloperoxidase – on the functions of HDL-cholesterol. It is well documented that disturbed circulating lipoproteins (a high total and high LDL-cholesterol, and low HDL-cholesterol bring about atherosclerosis and an increased risk of cardiovascular disease (CVD which is recognised as the main cause of death all around the world. In consequence, numerous studies have focused on procedures which will improve the plasma lipoproteins profile by decreasing the total cholesterol and the LDL-cholesterol (LDL-C and increasing the HDL-cholesterol (HDL-C. However, the anti-atherogenic role of HDL-C has been challenged in studies showing that genetically elevated HDL-cholesterol does not offer protection against CVD. Moreover, it has been found that raising the circulating HDL-cholesterol fails to reduce atherosclerosis. The doubts concerning the protective role of HDL-C have been supported by in vitro studies which indicate that the HDL-C from patients with atherosclerosis does not have a protective action, but does stimulate inflammation and free radical synthesis. The above data suggests that HDL-C, commonly recognised as protective against atherosclerosis, in some circumstances becomes pro-atherogenic, and is thus dysfunctional. Our review focuses on two enzymes – paraoxonase 1 (PON1 and myeloperoxidase (MPO – which markedly affect the properties of HDL-C and contribute to its anti – or pro-atherogenic activity. Moreover, the effects of the diet and physical activity on PON1 and MPO are summarised with respect to the HDL-C functionality.

  16. Evaluation of oxidative stress status and antioxidant capacity in patients with renal cell carcinoma.

    Science.gov (United States)

    Aldemir, Mustafa; Karaguzel, Ersagun; Okulu, Emrah; Gudeloglu, Ahmet; Ener, Kemal; Ozayar, Asim; Erel, Ozcan

    2015-01-01

    We evaluated and compared the serum oxidative stress and antioxidant enzymes in patients with renal cell carcinoma (RCC) and the control group. The prospective study consisted of 97 patients with RCC (Group 1) and 80 age and sex matched healthy volunteers (Group 2). Group 1 and 2 were compared concerning serum mean total oxidant status (TOS), total antioxidant capacity (TAC), paraoxonase-1 (PON-1), arylesterase, total thiol, catalase (CAT), myeloperoxidase (MPO) and ceruloplasmin. Patients' mean age was 58.5 ±12.3 and 56.9 ±15.8 years, respectively, in Group 1 and 2. No statistically significant differences were detected between the groups in terms of oxidative stress parameters and antioxidant capacity measured in the serum of patients including, TOS, TAC, PON1, arylesterase, total thiol, CAT, MPO, and ceruloplasmin levels (p >0.05 for all parameters). The PON-1 value was significantly higher in patients with pT1 stage than pT3 stage (p = 0.007). The arylesterase value was significantly higher in patients with Fuhrman's nuclear grade 3 than grade 2 (p = 0.035). There was no correlation between these parameters level and Fuhrman's nuclear grade, stage, or histopathological tumor type. Our results demonstrated that evaluation of these parameters in the serum of patients with localized RCC may not be used as a marker to discriminate between patients with RCC and healthy people.

  17. Wavelength Tuning Free Transceiver Module in OLT Downstream Multicasting 4λ × 10 Gb/s TWDM-PON System

    OpenAIRE

    M. S. Salleh; A. S. M. Supa’at; S. M. Idrus; S. Yaakob; Z. M. Yusof

    2014-01-01

    We propose a new architecture of dynamic time-wavelength division multiplexing-passive optical network (TWDM-PON) system that employs integrated all-optical packet routing (AOPR) module using 4λ×10 Gbps downstream signal to support 20 km fiber transmission. This module has been designed to support high speed L2 aggregation and routing in the physical layer PON system by using multicasting cross-gain modulation (XGM) to route packet from any PON port to multiple PON links. Meanwhile, the fixed...

  18. Un enfoque probabilístico en la autorreparación de redes G-PON

    Directory of Open Access Journals (Sweden)

    J. García-Algarra

    2014-01-01

    Full Text Available Resumen: El despliegue de accesos de fibra óptica hasta los hogares (Fiber To The Home, FTTH en adelante es una prioridad de los operadores de telecomunicación para soportar nuevos servicios digitales y mejorar la experiencia de los usuarios. G-PON es la tecnología más común; su instalación plantea importantes retos en el diagnóstico y reparación de averías de esta infraestructura, de características muy diferentes a las de los tradicionales pares de cobre. En este artículo presentamos una experiencia basada en un enfoque probabilístico del problema. Copyright © 2014 CEA. Publicado por Elsevier España, S.L. Todos los derechos reservados. Abstract: Fiber To The Home (FTTH rollout is a priority for telecom operators to provide fixed broadband new services and improve customer experience. G-PON is the most common technical choice that creates new challenges related to diagnosis and self healing. A probabilistic approach has been evaluated in a lab environment to overcome the uncertainties of this scenario, and results that is suitable for live network. Palabras clave: FTTH, G-PON, red bayesiana, agentes, autorreparación., Keywords: FTTH, G-PON, Bayesian Network, agents, self healing.

  19. Electrical insulation properties of RF-sputtered LiPON layers towards electrochemical stability of lithium batteries

    OpenAIRE

    Vieira, E. M. F.; Ribeiro, J. F.; Silva, Maria Manuela; Barradas, N. P.; Alves, E.; Alves, A.; Correia, M. R.; Gonçalves, L. M.

    2016-01-01

    Electrochemical stability, moderate ionic conductivity and low electronic conductivity make the lithium phosphorous oxynitride (LiPON) electrolyte suitable for micro and nanoscale lithium batteries. The electrical and electrochemical properties of thin-film electrolytes can seriously compromise full battery performance. Here, radio-frequency (RF)-sputtered LiPON thin films were fabricated in nitrogen plasma under different working pressure conditions. With a slight decrease in ...

  20. Energy-efficient WDM-OFDM-PON employing shared OFDM modulation modules in optical line terminal.

    Science.gov (United States)

    Hu, Xiaofeng; Zhang, Liang; Cao, Pan; Wang, Kongtao; Su, Yikai

    2012-03-26

    We propose and experimentally demonstrate a scheme to improve the energy efficiency of wavelength division multiplexing - orthogonal frequency division multiplexing - passive optical networks (WDM-OFDM-PONs). By using an N × M opto-mechanic switch in optical line terminal (OLT), an OFDM modulation module is shared by several channels to deliver data to multiple users with low traffic demands during non-peak hours of the day, thus greatly reducing the number of operating devices and minimizing the energy consumption of the OLT. An experiment utilizing one OFDM modulation module to serve three optical network units (ONUs) in a WDM-OFDM-PON is performed to verify the feasibility of our proposal. Theoretical analysis and numerical calculation show that the proposed scheme can achieve a saving of 23.6% in the energy consumption of the OFDM modulation modules compared to conventional WDM-OFDM-PON.

  1. Comparison of Bit Error Rate of Line Codes in NG-PON2

    Directory of Open Access Journals (Sweden)

    Tomas Horvath

    2016-05-01

    Full Text Available This article focuses on simulation and comparison of line codes NRZ (Non Return to Zero, RZ (Return to Zero and Miller’s code for NG-PON2 (Next-Generation Passive Optical Network Stage 2 using. Our article provides solutions with Q-factor, BER (Bit Error Rate, and bandwidth comparison. Line codes are the most important part of communication over the optical fibre. The main role of these codes is digital signal representation. NG-PON2 networks use optical fibres for communication that is the reason why OptSim v5.2 is used for simulation.

  2. Demonstration and field trial of a resilient hybrid NG-PON test-bed

    Science.gov (United States)

    Prat, Josep; Polo, Victor; Schrenk, Bernhard; Lazaro, Jose A.; Bonada, Francesc; Lopez, Eduardo T.; Omella, Mireia; Saliou, Fabienne; Le, Quang T.; Chanclou, Philippe; Leino, Dmitri; Soila, Risto; Spirou, Spiros; Costa, Liliana; Teixeira, Antonio; Tosi-Beleffi, Giorgio M.; Klonidis, Dimitrios; Tomkos, Ioannis

    2014-10-01

    A multi-layer next generation PON prototype has been built and tested, to show the feasibility of extended hybrid DWDM/TDM-XGPON FTTH networks with resilient optically-integrated ring-trees architecture, supporting broadband multimedia services. It constitutes a transparent common platform for the coexistence of multiple operators sharing the optical infrastructure of the central metro ring, passively combining the access and the metropolitan network sections. It features 32 wavelength connections at 10 Gbps, up to 1000 users distributed in 16 independent resilient sub-PONs over 100 km. This paper summarizes the network operation, demonstration and field trial results.

  3. Daily moderate alcohol consumption increases serum paraoxonase activity; a diet-controlled, randomised intervention study in middle-aged men

    NARCIS (Netherlands)

    Gaag, M.S. van der; Tol, A. van; Scheek, L.M.; James, R.W.; Urgert, R.; Schaafsma, G.; Hendriks, H.F.J.

    1999-01-01

    Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Part of this inverse association may be explained by its effects on HDL. Paraoxonase, an HDL-associated enzyme, has been suggested to protect against LDL oxidation. We examined the effects of moderate

  4. Traffic-aware energy saving scheme with modularization supporting in TWDM-PON

    Science.gov (United States)

    Xiong, Yu; Sun, Peng; Liu, Chuanbo; Guan, Jianjun

    2017-01-01

    Time and wavelength division multiplexed passive optical network (TWDM-PON) is considered to be a primary solution for next-generation passive optical network stage 2 (NG-PON2). Due to the feature of multi-wavelength transmission of TWDM-PON, some of the transmitters/receivers at the optical line terminal (OLT) could be shut down to reduce the energy consumption. Therefore, a novel scheme called traffic-aware energy saving scheme with modularization supporting is proposed. Through establishing the modular energy consumption model of OLT, the wavelength transmitters/receivers at OLT could be switched on or shut down adaptively depending on sensing the status of network traffic load, thus the energy consumption of OLT will be effectively reduced. Furthermore, exploring the technology of optical network unit (ONU) modularization, each module of ONU could be switched to sleep or active mode independently in order to reduce the energy consumption of ONU. Simultaneously, the polling sequence of ONU could be changed dynamically via sensing the packet arrival time. In order to guarantee the delay performance of network traffic, the sub-cycle division strategy is designed to transmit the real-time traffic preferentially. Finally, simulation results verify that the proposed scheme is able to reduce the energy consumption of the network while maintaining the traffic delay performance.

  5. Extended reach OFDM-PON using super-Nyquist image induced aliasing.

    Science.gov (United States)

    Guo, Changjian; Liang, Jiawei; Liu, Jie; Liu, Liu

    2015-08-24

    We investigate a novel dispersion compensating technique in double sideband (DSB) modulated and directed-detected (DD) passive optical network (PON) systems using super-Nyquist image induced aliasing. We show that diversity is introduced to the higher frequency components by deliberate aliasing using the super-Nyquist images. We then propose to use fractional sampling and per-subcarrier maximum ratio combining (MRC) to harvest this diversity. We evaluate the performance of conventional orthogonal frequency division multiplexing (OFDM) signals along with discrete Fourier transform spread (DFT-S) OFDM and code-division multiplexing OFDM (CDM-OFDM) signals using the proposed scheme. The results show that the DFT-S OFDM signal has the best performance due to spectrum spreading and its superior peak-to-average power ratio (PAPR). By using the proposed scheme, the reach of a 10-GHz bandwidth QPSK modulated OFDM-PON can be extended to around 90 km. We also experimentally show that the achievable data rate of the OFDM signals can be effectively increased using the proposed scheme when adaptive bit loading is applied, depending on the transmission distance. A 10.5% and 5.2% increase in the achievable bit rate can be obtained for DSB modulated OFDM-PONs in 48.3-km and 83.2-km standard single mode fiber (SSMF) transmission cases, respectively, without any modification on the transmitter. A 40-Gb/s OFDM transmission over 83.2-km SSMF is successfully demonstrated.

  6. Remote-seeded WDM-PON upgrade using linear semiconductor opticalamplifiers

    Science.gov (United States)

    Martínez, J. J.; Merayo, N.; Villafranca, A.; Garcés, I.

    2013-05-01

    In this work we have assessed the capacity of a linear (gain-clamped) semiconductor optical amplifier to enhance the budget of WDM PON network links for their evolution from FTTC to FTTH access. A wavelength-seeded network architecture has been considered, evaluating the performance improvement obtained by the use of an amplifier for the cases of link reach extension and optical splitting to reach end users. The evaluation measurements have shown that the extra budget is enough to compensate for the losses of a passive splitter up to atleast 1:16 division rate or to highly increment reach of the network.

  7. A chaotic modified-DFT encryption scheme for physical layer security and PAPR reduction in OFDM-PON

    Science.gov (United States)

    Fu, Xiaosong; Bi, Meihua; Zhou, Xuefang; Yang, Guowei; Li, Qiliang; Zhou, Zhao; Yang, Xuelin

    2018-05-01

    This letter proposes a modified discrete Fourier transform (DFT) encryption scheme with multi-dimensional chaos for the physical layer security and peak-to-average power ratio (PAPR) reduction in orthogonal frequency division multiplexing passive optical network (OFDM-PON) system. This multiple-fold encryption algorithm is mainly composed by using the column vectors permutation and the random phase encryption in the standard DFT matrix, which can create ∼10551 key space. The transmission of ∼10 Gb/s encrypted OFDM signal is verified over 20-km standard single mode fiber (SMF). Moreover, experimental results show that, the proposed scheme can achieve ∼2.6-dB PAPR reduction and ∼1-dB improvement of receiver sensitivity if compared with the common OFDM-PON.

  8. Self-healing ring-based WDM-PON

    Science.gov (United States)

    Zhou, Yang; Gan, Chaoqin; Zhu, Long

    2010-05-01

    In this paper, a survivable ring-based wavelength-division-multiplexing (WDM)-passive optical network (PON) for fiber protection is proposed. Protections for feeder fiber and distributed fiber are independent in the scheme. Optical line terminal (OLT) and optical network units (ONUs) can automatically switch to protection link when fiber failure occurs. Protection distributed fiber is not required in the scheme. Cost-effective components are used in ONUs to minimize costs of network. A simulation study is performed to demonstrate the scheme. Its result shows good performance of upstream and downstream signals.

  9. Mathematical Verification for Transmission Performance of Centralized Lightwave WDM-RoF-PON with Quintuple Services Integrated in Each Wavelength Channel

    Directory of Open Access Journals (Sweden)

    Shuai Chen

    2015-01-01

    Full Text Available Wavelength-division-multiplexing passive-optical-network (WDM-PON has been recognized as a promising solution of the “last mile” access as well as multibroadband data services access for end users, and WDM-RoF-PON, which employs radio-over-fiber (RoF technique in WDM-PON, is even a more attractive approach for future broadband fiber and wireless access for its strong availability of centralized multiservices transmission operation and its transparency for bandwidth and signal modulation formats. As for multiservices development in WDM-RoF-PON, various system designs have been reported and verified via simulation or experiment till now, and the scheme with multiservices transmitted in each single wavelength channel is believed as the one that has the highest bandwidth efficiency; however, the corresponding mathematical verification is still hard to be found in state-of-the-art literature. In this paper, system design and data transmission performance of a quintuple services integrated WDM-RoF-PON which jointly employs carrier multiplexing and orthogonal modulation techniques, have been theoretically analyzed and verified in detail; moreover, the system design has been duplicated and verified experimentally and the theory system of such WDM-RoF-PON scheme has thus been formed.

  10. Security scheme in IMDD-OFDM-PON system with the chaotic pilot interval and scrambling

    Science.gov (United States)

    Chen, Qianghua; Bi, Meihua; Fu, Xiaosong; Lu, Yang; Zeng, Ran; Yang, Guowei; Yang, Xuelin; Xiao, Shilin

    2018-01-01

    In this paper, a random chaotic pilot interval and permutations scheme without any requirement of redundant sideband information is firstly proposed for the physical layer security-enhanced intensity modulation direct detection orthogonal frequency division multiplexing passive optical network (IMDD-OFDM-PON) system. With the help of the position feature of inserting the pilot, a simple logistic chaos map is used to generate the random pilot interval and scramble the chaotic subcarrier allocation of each column pilot data for improving the physical layer confidentiality. Due to the dynamic chaotic permutations of pilot data, the enhanced key space of ∼103303 is achieved in OFDM-PON. Moreover, the transmission experiment of 10-Gb/s 16-QAM encrypted OFDM data is successfully demonstrated over 20-km single-mode fiber, which indicates that the proposed scheme not only improves the system security, but also can achieve the same performance as in the common IMDD-OFDM-PON system without encryption scheme.

  11. Performance Analysis of Long-Reach Coherent Detection OFDM-PON Downstream Transmission Using m-QAM-Mapped OFDM Signal

    Science.gov (United States)

    Pandey, Gaurav; Goel, Aditya

    2017-12-01

    In this paper, orthogonal frequency division multiplexing (OFDM)-passive optical network (PON) downstream transmission is demonstrated over different lengths of fiber at remote node (RN) for different m-QAM (quadrature amplitude modulation)-mapped OFDM signal (m=4, 16, 32 and 64) transmission from the central office (CO) for different data rates (10, 20 30 and 40 Gbps) using coherent detection at the user end or optical network unit (ONU). Investigation is performed with different number of subcarriers (32, 64, 128, 512 and 1,024), back-to-back optical signal-to-noise ratio (OSNR) along with transmitted and received constellation diagrams for m-QAM-mapped coherent OFDM downstream transmission at different speeds over different transmission distances. Received optical power is calculated for different bit error rates (BERs) at different speeds using m-QAM-mapped coherent detection OFDM downstream transmission. No dispersion compensation is utilized in between the fiber span. Simulation results suggest the different lengths and data rates that can be used for different m-QAM-mapped coherent detection OFDM downstream transmission, and the proposed system may be implemented in next-generation high-speed PONs (NG-PONs).

  12. Proposta, simulação e testes de arquitetura para redes ópticas passivas GPON e XG-PON

    OpenAIRE

    Rodrigo Alves Cardoso

    2015-01-01

    Resumo: O objetivo deste trabalho foi propor uma arquitetura de rede óptica passiva (PON) capaz de suportar um sistema GPON e permitir a evolução para redes PON de nova geração, ou XG-PON, de maneira que ambas as tecnologias possam coexistir na mesma infraestrutura de rede óptica. Na arquitetura foram considerados um mecanismo de proteção parcial e equipamentos que possibilitam sua efetiva construção. Foi apresentado um modelo matemático que permitiu a validação da arquitetura em função do cá...

  13. 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.

  14. Two-dimensional priority-based dynamic resource allocation algorithm for QoS in WDM/TDM PON networks

    Science.gov (United States)

    Sun, Yixin; Liu, Bo; Zhang, Lijia; Xin, Xiangjun; Zhang, Qi; Rao, Lan

    2018-01-01

    Wavelength division multiplexing/time division multiplexing (WDM/TDM) passive optical networks (PON) is being viewed as a promising solution for delivering multiple services and applications. The hybrid WDM / TDM PON uses the wavelength and bandwidth allocation strategy to control the distribution of the wavelength channels in the uplink direction, so that it can ensure the high bandwidth requirements of multiple Optical Network Units (ONUs) while improving the wavelength resource utilization. Through the investigation of the presented dynamic bandwidth allocation algorithms, these algorithms can't satisfy the requirements of different levels of service very well while adapting to the structural characteristics of mixed WDM / TDM PON system. This paper introduces a novel wavelength and bandwidth allocation algorithm to efficiently utilize the bandwidth and support QoS (Quality of Service) guarantees in WDM/TDM PON. Two priority based polling subcycles are introduced in order to increase system efficiency and improve system performance. The fixed priority polling subcycle and dynamic priority polling subcycle follow different principles to implement wavelength and bandwidth allocation according to the priority of different levels of service. A simulation was conducted to study the performance of the priority based polling in dynamic resource allocation algorithm in WDM/TDM PON. The results show that the performance of delay-sensitive services is greatly improved without degrading QoS guarantees for other services. Compared with the traditional dynamic bandwidth allocation algorithms, this algorithm can meet bandwidth needs of different priority traffic class, achieve low loss rate performance, and ensure real-time of high priority traffic class in terms of overall traffic on the network.

  15. Cost-effective TCM-based WDM-PON for highly asymmetric traffic conditions.

    Science.gov (United States)

    Lee, Danbi; Kwon, Won-Bae; Chae, Chang-Joon; Park, Chang-Soo

    2015-11-16

    A time compression multiplexing (TCM)-based wavelength division multiplexing passive optical network (WDM-PON) using a reflective semiconductor optical amplifier (RSOA) is proposed, and its feasibility is experimentally demonstrated. In the proposed system, the RSOA pre-amplifies a 10 Gb/s downstream signal and modulates the RSOA output, wavelength-locked to the downstream signal, with a 1.25 Gb/s upstream signal simultaneously. The sensitivity of the downstream signal is improved by about 3 dB through the RSOA. The downstream and upstream signals have power penalties of about 0.1 dB and 1.1 dB, respectively, at bit error rates (BERs) of 10(-9) after 20 km transmission.

  16. Design and implementation of flexible TWDM-PON with PtP WDM overlay based on WSS for next-generation optical access networks

    Science.gov (United States)

    Wu, Bin; Yin, Hongxi; Qin, Jie; Liu, Chang; Liu, Anliang; Shao, Qi; Xu, Xiaoguang

    2016-09-01

    Aiming at the increasing demand of the diversification services and flexible bandwidth allocation of the future access networks, a flexible passive optical network (PON) scheme combining time and wavelength division multiplexing (TWDM) with point-to-point wavelength division multiplexing (PtP WDM) overlay is proposed for the next-generation optical access networks in this paper. A novel software-defined optical distribution network (ODN) structure is designed based on wavelength selective switches (WSS), which can implement wavelength and bandwidth dynamical allocations and suits for the bursty traffic. The experimental results reveal that the TWDM-PON can provide 40 Gb/s downstream and 10 Gb/s upstream data transmission, while the PtP WDM-PON can support 10 GHz point-to-point dedicated bandwidth as the overlay complement system. The wavelengths of the TWDM-PON and PtP WDM-PON are allocated dynamically based on WSS, which verifies the feasibility of the proposed structure.

  17. Extrastriatal binding of [¹²³I]FP-CIT in the thalamus and pons

    DEFF Research Database (Denmark)

    Koch, Walter; Unterrainer, Marcus; Xiong, Guoming

    2014-01-01

    extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. METHODS: SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes...... error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. CONCLUSION: The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [(123)I]FP-CIT scans in healthy controls. For both...... the thalamus and the pons, an age-related decline in radiotracer binding was observed. Gender effects were demonstrated for binding in the thalamus only. As a potential clinical application, the data could be used as a reference to estimate SERT occupancy in addition to nigrostriatal integrity when using [(123...

  18. Arylesterase Phenotype-Specific Positive Association Between Arylesterase Activity and Cholinesterase Specific Activity in Human Serum

    Directory of Open Access Journals (Sweden)

    Yutaka Aoki

    2014-01-01

    Full Text Available Context: Cholinesterase (ChE specific activity is the ratio of ChE activity to ChE mass and, as a biomarker of exposure to cholinesterase inhibitors, has a potential advantage over simple ChE activity. Objective: To examine the association of several potential correlates (serum arylesterase/paraoxonase activity, serum albumin, sex, age, month of blood collection, and smoking with plasma ChE specific activity. Methods: We analyzed data from 195 cancer-free controls from a nested case-control study, accounting for potential confounding. Results: Arylesterase activity had an independent, statistically significant positive association with ChE specific activity, and its magnitude was the greatest for the arylesterase phenotype corresponding to the QQ PON1192 genotype followed by phenotypes corresponding to QR and RR genotypes. Serum albumin was positively associated with ChE specific activity. Conclusions: Plasma arylesterase activity was positively associated with plasma ChE specific activity. This observation is consistent with protection conferred by a metabolic phenotype resulting in reduced internal dose.

  19. Oxidant-antioxidant status in Egyptian children with sickle cell anemia: a single center based study.

    Science.gov (United States)

    El-Ghamrawy, Mona Kamal; Hanna, Wagdi Maurice; Abdel-Salam, Amina; El-Sonbaty, Marwa M; Youness, Eman R; Adel, Ahmed

    2014-01-01

    the present study was conducted to investigate the oxidant-antioxidant status in Egyptian children with sickle cell anemia. the serum levels of total antioxidant capacity (TAO), paraoxonase (PON), vitamin E, nitrite, and malondialdehyde (MDA) were measured in 40 steady state children with homozygous sickle cell anemia (24 males and 16 females) and 20 apparently healthy age- and gender-matched controls. mean serum TAO, PON, vitamin E, and nitrite levels were significantly lower in the group with sickle cell anemia, whereas mean serum MDA was significantly higher in these children compared to controls. No significant differences in mean levels of TAO, PON, nitrite, vitamin E, and MDA were found in sickle cell anemia patients receiving hydroxyurea when compared with those not receiving hydroxyurea. A significant negative correlation between serum nitrite and the occurrence of vaso-occlusive crises (VOC) was observed (r=-0.3, p=0.04). PON level was found to be positively correlated with patients' weight and BMI (r=-0.4, p=0.01; r=-0.7, panemia have chronic oxidative stress that may result in increased VOC, and decreased serum nitrite may be associated with increases in VOC frequency. A novel finding in this study is the decrease in PON level in these patients, which is an interesting subject for further research. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  20. Study on the capability of four-level partial response equalization in RSOA-based WDM-PON

    Science.gov (United States)

    Guo, Qi; Tran, An Vu

    2010-12-01

    The expected development of advanced video services with HDTV quality demands the delivery of more than Gb/s link to end users across the last mile connection. Future access networks are also required to have long reach for reduction in the number of central offices (CO). Fueled by those requirements, we propose a novel equalization scheme that increases the capacity and reach of the wavelength division multiplexing passive optical network (WDM-PON) based on a low bandwidth reflective semiconductor optical amplifier (RSOA). We investigate the characteristics of 10 Gb/s upstream transmission in WDM-PON using RSOA with only 1.2 GHz electrical bandwidth and various lengths of fiber. It is proven that the proposed four-level partial response equalizer (PRE) is capable of mitigating the impact of ISI in the received signals from optical network units (ONU) located 0 km to 75 km away from the optical line terminal (OLT).

  1. Langerhans cell histiocytosis with involvement of the pons: case report

    International Nuclear Information System (INIS)

    Vourtsi, A.; Papadopoulos, A.; Moulopoulos, L.A.; Vlahos, L.; Xenellis, J.

    1998-01-01

    Central nervous system involvement is uncommon in Langerhans cell histiocytosis. The suprasellar region is more frequently affected. There have been few reports of involvement of the brain parenchyma shown on CT or MRI. We present a case of involvement of the pons, showing marked contrast enhancement on MRI. (orig.)

  2. MIMO-OFDM WDM PON with DM-VCSEL for femtocells application

    DEFF Research Database (Denmark)

    Binti Othman, Maisara; Deng, Lei; Pang, Xiaodan

    2011-01-01

    We report on experimental demonstration of 2x2 MIMO-OFDM 5.6-GHz radio over fiber signaling over 20 km WDM-PON with directly modulated (DM) VCSELs for femtocells application. MIMO-OFDM algorithms effectively compensate for impairments in the wireless link. Error-free signal demodulation of 64...

  3. MRI measurements of the pons and cerebellum in children born preterm; associations with the severity of periventricular leukomalacia and perinatal risk factors

    International Nuclear Information System (INIS)

    Argyropoulou, M.I.; Xydis, V.; Argyropoulou, P.I.; Efremidis, S.C.; Drougia, A.; Andronikou, S.; Tzoufi, M.; Bassounas, A.

    2003-01-01

    Our purpose was to measure the size of the pons and cerebellum in preterm babies with periventricular leukomalacia (PVL), and to study their relationship with the severity of PVL and with perinatal risk factors. We examined 33 premature children, mean gestational age 31 weeks, range 26-36 weeks with PVL on MRI, and 27 full-term controls. On MRI at 0.4-5.5 years (mean 1.4 years) we measured the area of the corpus callosum and vermis, the anteroposterior diameter of the pons and the volume of the cerebellum. The area of the corpus callosum was used as a marker of white matter loss and PVL severity. All regional brain measurements except that of the vermis were significantly lower in patients than controls: corpus callosum (mm 2 ): 239.6±92.5 vs 434.8±126.8, P 3 ): 68.2±31.6 vs 100.6±28.3, P 2 ): 808.1±292.2 vs 942.2±246.2, NS. Significant reduction in the area of the vermis: 411.3±203.3 vs 935±252.6 mm 2 ; cerebellar volume: 16.3±12.5 vs 96.6±20.2 mm 3 ; and the diameter of the pons: 10.1±2.2 vs 17.5±1.3 mm (P <0.01) were observed in seven children with gestational age ≤28 weeks, severe hypotension and large patent ductus arteriosus (PDA). There was a significant correlation between the duration of mechanical ventilation and the size of the vermis, pons and cerebellum (R=-0.65, -0.57 and -0.73, respectively, P <0.01). (orig.)

  4. All-optical virtual private network system in OFDM based long-reach PON using RSOA re-modulation technique

    Science.gov (United States)

    Kim, Chang-Hun; Jung, Sang-Min; Kang, Su-Min; Han, Sang-Kook

    2015-01-01

    We propose an all-optical virtual private network (VPN) system in an orthogonal frequency division multiplexing (OFDM) based long reach PON (LR-PON). In the optical access network field, technologies based on fundamental upstream (U/S) and downstream (D/S) have been actively researched to accommodate explosion of data capacity. However, data transmission among the end users which is arisen from cloud computing, file-sharing and interactive game takes a large weight inside of internet traffic. Moreover, this traffic is predicted to increase more if Internet of Things (IoT) services are activated. In a conventional PON, VPN data is transmitted through ONU-OLT-ONU via U/S and D/S carriers. It leads to waste of bandwidth and energy due to O-E-O conversion in the OLT and round-trip propagation between OLT and remote node (RN). Also, it causes inevitable load to the OLT for electrical buffer, scheduling and routing. The network inefficiency becomes more critical in a LR-PON which has been researched as an effort to reduce CAPEX and OPEX through metro-access consolidation. In the proposed system, the VPN data is separated from conventional U/S and re-modulated on the D/S carrier by using RSOA in the ONUs to avoid bandwidth consumption of U/S and D/S unlike in previously reported system. Moreover, the transmitted VPN data is re-directed to the ONUs by wavelength selective reflector device in the RN without passing through the OLT. Experimental demonstration for the VPN communication system in an OFDM based LR-PON has been verified.

  5. 40 Gb/s Lane Rate NG-PON using Electrical/Optical Duobinary, PAM-4 and Low Complex Equalizations

    DEFF Research Database (Denmark)

    Wei, J. L.; Grobe, Klaus; Wagner, Christoph

    2016-01-01

    We present the first numerical investigation and comparison of 40-Gb/s lane rate electrical Duobinary, optical Duobinary and PAM-4 for NG-PONs incorporating low complex linear and nonlinear post-equalizations.......We present the first numerical investigation and comparison of 40-Gb/s lane rate electrical Duobinary, optical Duobinary and PAM-4 for NG-PONs incorporating low complex linear and nonlinear post-equalizations....

  6. Virtualización de xPON con SDN

    OpenAIRE

    Mesones Ruiz, Antonio

    2016-01-01

    Virtualization of different families of Passive Optical access Networks following the new Software-Defined Networking (SDN) paradigm SDN is a novel paradigm that enables more efficient operation and management in networks, by centralizing some functions that are distributed in the current network architectures. SIEPON is a novel standard that adds functionality to EPON, not covered by any current PON standard. We propose an implementation of SDN on SIEPON, improving flexibility and efficie...

  7. Induced overexpression of protein kinase D1 stimulates mitogenic signaling in human pancreatic carcinoma PANC-1 cells.

    Science.gov (United States)

    Kisfalvi, Krisztina; Hurd, Cliff; Guha, Sushovan; Rozengurt, Enrique

    2010-05-01

    Neurotensin (NT) stimulates protein kinase D1 (PKD1), extracellular signal regulated kinase (ERK), c-Jun N-terminal Kinase (JNK), and DNA synthesis in the human pancreatic adenocarcinoma cell line PANC-1. To determine the effect of PKD1 overexpression on these biological responses, we generated inducible stable PANC-1 clones that express wild-type (WT) or kinase-dead (K618N) forms of PKD1 in response to the ecdysone analog ponasterone-A (PonA). NT potently stimulated c-Jun Ser(63) phosphorylation in both wild type and clonal derivatives of PANC-1 cells. PonA-induced expression of WT, but not K618N PKD1, rapidly blocked NT-mediated c-Jun Ser(63) phosphorylation either at the level of or upstream of MKK4, a dual-specificity kinase that leads to JNK activation. This is the first demonstration that PKD1 suppresses NT-induced JNK/cJun activation in PANC-1 cells. In contrast, PKD1 overexpression markedly increased the duration of NT-induced ERK activation in these cells. The reciprocal influence of PKD1 signaling on pro-mitogenicERK and pro-apopotic JNK/c-Jun pathways prompted us to examine whether PKD1 overexpression promotes DNA synthesis and proliferation of PANC-1 cells. Our results show that PKD1 overexpression increased DNA synthesis and cell numbers of PANC-1 cells cultured in regular dishes or in polyhydroxyethylmethacrylate [Poly-(HEMA)]-coated dishes to eliminate cell adhesion (anchorage-independent growth). Furthermore, PKD1 overexpression markedly enhanced DNA synthesis induced by NT (1-10 nM). These results indicate that PKD1 mediates mitogenic signaling in PANC-1 and suggests that this enzyme could be a novel target for the development of therapeutic drugs that restrict the proliferation of these cells.

  8. Role of Genetic Background in Cardiovascular Risk Markers Changes in Water Polo Players.

    Science.gov (United States)

    Di Mauro, Debora; Currò, Monica; Trimarchi, Fabio; Vecchio, Mercurio; Rizzo, Giuseppina; Barreca, Davide; Visalli, Giuseppa; Ientile, Riccardo; Caccamo, Daniela

    2018-05-01

    Methylene-tetrahydrofolate reductase (MTHFR) and paraoxonase 1 (PON1) gene polymorphisms have been associated with hyperhomocysteinemia and oxidative stress increase, that are established cardiovascular risk factors. Given that intense physical activity may increase the susceptibility to adverse cardiovascular outcomes, here we investigated the effects of MTHFR C677T and A1298C as well as PON1 Q192R gene polymorphisms on cardiovascular risk markers in twenty-eight male water polo elite players. The mean plasma levels of homocysteine (Hcy) and advanced oxidation protein products (AOPP) were above reference limits in resting conditions, and increased after competition. Moreover, a positive correlation was found between Hcy and AOPP concentrations, and also between their variations (ratio post-exercise/pre-exercise values) and the variations of lactic dehydrogenase (LDH) and creatine kinase (CK) activities, known as muscle damage markers. The highest Hcy and AOPP values were found in subjects having either MTHFR CT/AC or TT/AA, and PON1 QR192 genotype, respectively. After exercise, Hcy concentrations significantly increased in CT/AC or TT/AA subjects than in athletes having other MTHFR genotypes. A training-induced increase in plasma levels of LDH and CK activities, as well as myoglobin concentrations, was also observed, even if significant differences were found only for CK activity in athletes with MTHFR CT/AC or TT/AA athletes. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Resource management research in Passive Optical Networks (PON)

    OpenAIRE

    Garfias Hernández, Paola

    2013-01-01

    Next Generation Access Networks (NGAN) are the new step forward to deliver broadband services and to facilitate the integration of different technologies. It is plausible to assume that, from a technological standpoint, the Future Internet will be composed of long-range high-speed optical networks; a number of wireless networks at the edge; and, in between, several access technologies, among which, the Passive Optical Networks (xPON) are very likely to succeed, due to their simplicity, low-co...

  10. Langerhans cell histiocytosis with involvement of the pons: case report

    Energy Technology Data Exchange (ETDEWEB)

    Vourtsi, A. [Xatzopoulou, Athens (Greece)]|[Department of Radiology, University of Athens Medical School, Athens (Greece); Papadopoulos, A.; Moulopoulos, L.A.; Vlahos, L. [Department of Radiology, University of Athens Medical School, Athens (Greece); Xenellis, J. [Department of Otorhinolaryngology, University of Athens Medical School, Athens (Greece)

    1998-03-01

    Central nervous system involvement is uncommon in Langerhans cell histiocytosis. The suprasellar region is more frequently affected. There have been few reports of involvement of the brain parenchyma shown on CT or MRI. We present a case of involvement of the pons, showing marked contrast enhancement on MRI. (orig.) With 2 figs., 17 refs.

  11. Multi-granularity Bandwidth Allocation for Large-Scale WDM/TDM PON

    Science.gov (United States)

    Gao, Ziyue; Gan, Chaoqin; Ni, Cuiping; Shi, Qiongling

    2017-12-01

    WDM (wavelength-division multiplexing)/TDM (time-division multiplexing) PON (passive optical network) is being viewed as a promising solution for delivering multiple services and applications, such as high-definition video, video conference and data traffic. Considering the real-time transmission, QoS (quality of services) requirements and differentiated services model, a multi-granularity dynamic bandwidth allocation (DBA) in both domains of wavelengths and time for large-scale hybrid WDM/TDM PON is proposed in this paper. The proposed scheme achieves load balance by using the bandwidth prediction. Based on the bandwidth prediction, the wavelength assignment can be realized fairly and effectively to satisfy the different demands of various classes. Specially, the allocation of residual bandwidth further augments the DBA and makes full use of bandwidth resources in the network. To further improve the network performance, two schemes named extending the cycle of one free wavelength (ECoFW) and large bandwidth shrinkage (LBS) are proposed, which can prevent transmission from interruption when the user employs more than one wavelength. The simulation results show the effectiveness of the proposed scheme.

  12. High triglycerides and low high-density lipoprotein cholesterol lipid profile in rheumatoid arthritis: A potential link among inflammation, oxidative status, and dysfunctional high-density lipoprotein.

    Science.gov (United States)

    Rodríguez-Carrio, Javier; Alperi-López, Mercedes; López, Patricia; López-Mejías, Raquel; Alonso-Castro, Sara; Abal, Francisco; Ballina-García, Francisco J; González-Gay, Miguel Á; Suárez, Ana

    The interactions between inflammation and lipid profile in rheumatoid arthritis (RA) are poorly understood. The lipid profile study in RA has been biased toward lipoprotein levels, whereas those of triglycerides (TGs) and lipoprotein functionality have been underestimated. Since recent findings suggest a role for TG and TG-rich lipoproteins (TRL) on inflammation, we aimed to evaluate a combined lipid profile characterized by high TG and low high-density lipoprotein cholesterol levels (TG high HDL low ) in RA. Lipid profiles were analyzed in 113 RA patients, 113 healthy controls, and 27 dyslipemic subjects. Levels of inflammatory mediators, paraoxonase-1 (PON1) activity, and total antioxidant capacity were quantified in serum. PON1-rs662 status was evaluated by real-time polymerase chain reaction. The TG high HDL low profile was detected in 29/113 RA patients. Although no differences in prevalence compared with healthy controls or dyslipemic subjects were observed, this profile was associated with increased tumor necrosis factor α (P = .004), monocyte chemotactic protein (P = .004), interferon-gamma-inducible protein-10 (P = .018), and leptin (P < .001) serum levels in RA, where decreased PON1 activity and total antioxidant capacity were found. TG high HDL low prevalence was lower among anti-TNFα-treated patients (P = .004). When RA patients were stratified by PON1-rs662 status, these associations remained in the low-activity genotype (QQ). Finally, a poor clinical response on TNFα blockade was related to an increasing prevalence of the TG high HDL low profile over treatment (P = .021) and higher TRL levels at baseline (P = .042). The TG high HDL low profile is associated with systemic inflammation, decreased PON1 activity, and poor clinical outcome on TNFα blockade in RA, suggesting a role of TRL and HDL dysfunction as the missing link between inflammation and lipid profile. Copyright © 2017 National Lipid Association. Published by Elsevier Inc

  13. A 80 km reach fully passive WDM-PON based on reflective ONUs

    DEFF Research Database (Denmark)

    Presi, Marco; Proietti, Roberto; Prince, Kamau

    2008-01-01

    We propose a novel line coding combination (Inverse RZ coding in downlink and RZ in uplink) that extends the reach of WDM Passive Optical Networks based on Reflective SOAs with no in-line amplification. We achieved full downstream remodulation even when feeding the reflective SOA with power level...... as low as -35dBm, thus increasing the system power budget. We experimentally assessed this scheme for a fully passive, full-duplex and symmetrical 1.25Gb/s WDM-PON over a 80km G.652 feeder....

  14. Distributed fiber Raman amplification in long reach PON bidirectional access links

    DEFF Research Database (Denmark)

    Tafur Monroy, Idelfonso; Kjær, Rasmus; Öhman, Filip

    2008-01-01

    Distributed Raman fiber amplification is proposed and experimentally demonstrated to support long reach passive optical network (PON) links. An 80 km, bidirectional, single fiber link is demonstrated using both standard intensity optical modulators at 10 Gb/s and up to 7.5 Gb/s using novel...

  15. C-fos expression in the pons and medulla of the cat during carbachol-induced active sleep.

    Science.gov (United States)

    Yamuy, J; Mancillas, J R; Morales, F R; Chase, M H

    1993-06-01

    Microinjection of carbachol into the rostral pontine tegmentum of the cat induces a state that is comparable to naturally occurring active (REM, rapid eye movement) sleep. We sought to determine, during this pharmacologically induced behavioral state, which we refer to as active sleep-carbachol, the distribution of activated neuron within the pons and medulla using c-fos immunocytochemistry as a functional marker. Compared with control cats, which were injected with saline, active sleep-carbachol cats exhibited higher numbers of c-fos-expressing neurons in (1) the medial and portions of the lateral reticular formation of the pons and medulla, (2) nuclei in the dorsolateral rostral pons, (3) various raphe nuclei, including the dorsal, central superior, magnus, pallidus, and obscurus, (4) the medial and lateral vestibular, prepositus hypoglossi, and intercalatus nuclei, and (5) the abducens nuclei. On the other hand, the mean number of c-fos-expressing neurons found in the masseter, facial, and hypoglossal nuclei was lower in carbachol-injected than in control cats. The data indicate that c-fos expression can be employed as a marker of state-dependent neuronal activity. The specific sites in which there were greater numbers of c-fos-expressing neurons during active sleep-carbachol are discussed in relation to the state of active sleep, as well as the functional role that these sites play in generating the various physiological patterns of activity that occur during this state.

  16. A new architecture and MAC protocol for fully flexible hybrid WDM/TDM PON

    NARCIS (Netherlands)

    Das, G.; Lannoo, B.; Jung, H.D.; Koonen, A.M.J.; Colle, D.; Pickavet, M.; Demeester, P.

    2009-01-01

    In this paper we propose a novel architecture and MAC protocol for a scalable, cost effective WDM / TDM PON providing fully flexible dynamic bandwidth allocation for upstream and downstream data transmission.

  17. Extrastriatal binding of [123I]FP-CIT in the thalamus and pons: gender and age dependencies assessed in a European multicentre database of healthy controls

    International Nuclear Information System (INIS)

    Koch, Walter; Unterrainer, Marcus; Xiong, Guoming; Bartenstein, Peter; Diemling, Markus; Varrone, Andrea; Dickson, John C.; Tossici-Bolt, Livia; Sera, Terez; Asenbaum, Susanne; Booij, Jan; Kapucu, Ozlem L.; Kluge, Andreas; Ziebell, Morten; Darcourt, Jacques; Nobili, Flavio; Pagani, Marco; Hesse, Swen; Borght, Thierry Vander; Laere, Koen van; Tatsch, Klaus; La Fougere, Christian

    2014-01-01

    Apart from binding to the dopamine transporter (DAT), [ 123 I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes of interest analysis for the thalamus and the pons. Data were examined for gender and age effects as well as for potential influence of striatal DAT radiotracer binding. Thalamic binding was significantly higher than pons binding. Partial correlations showed an influence of putaminal DAT binding on measured binding in the thalamus but not on the pons. Data showed high interindividual variation in extrastriatal binding. Significant gender effects with 31 % higher binding in women than in men were observed in the thalamus, but not in the pons. An age dependency with a decline per decade (±standard error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [ 123 I]FP-CIT scans in healthy controls. For both the thalamus and the pons, an age-related decline in radiotracer binding was observed. Gender effects were demonstrated for binding in the thalamus only. As a potential clinical application, the data could be used as a reference to estimate SERT occupancy in addition to nigrostriatal integrity when using [ 123 I]FP-CIT for DAT imaging in patients treated with selective serotonin reuptake inhibitors. (orig.)

  18. 85 km Long Reach PON System Using a Reflective SOA-EA Modulator and Distributed Raman Fiber Amplification

    DEFF Research Database (Denmark)

    Tafur Monroy, Idelfonso; Öhman, Filip; Yvind, Kresten

    2006-01-01

    We report on a bidirectional 85 km long reach PON system supported by distributed fiber Raman amplification with a record 7.5 Gb/s remote carrier modulated upstream signal by employing a reflective SOA-EA monolithically integrated circuit......We report on a bidirectional 85 km long reach PON system supported by distributed fiber Raman amplification with a record 7.5 Gb/s remote carrier modulated upstream signal by employing a reflective SOA-EA monolithically integrated circuit...

  19. The effects of resveratrol on hepatic oxidative stress in metabolic syndrome model induced by high fructose diet.

    Science.gov (United States)

    Yilmaz Demirtas, C; Bircan, F S; Pasaoglu, O T; Turkozkan, N

    2018-01-01

    The purpose of this study was to evaluate probable protective effects of resveratrol treatment on hepatic oxidative events in a rat model of metabolic syndrome (MetS). Thirty-two male adult rats were randomly divided into 4 groups: control, fructose, resveratrol, and fructose plus resveratrol. To induce MetS, fructose solution (20 % in drinking water) was used. Resveratrol (10 mg/kg/day) was given by oral gavage. All treatments were given for 8 weeks. Serum lipid profile, glucose and insulin levels, liver total oxidant status (TOS) levels and paraoxonase (PON), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were analyzed. Fructose-fed rats displayed statistically significant increases in TOS levels, and decreases in PON activity compared to the control group. Resveratrol treatment moderately prevented the decrease in liver PON activity caused by fructose. On the other hand, resveratrol, alone or in combination with fructose, did not change the TOS levels when compared to the fructose group. The SOD and CAT activities in all groups did not change. In this experimental design, high-fructose consumption led to elevated TOS levels and low PON activities. The resveratrol therapy shown beneficial effects on PON activity. However, it was found to behave like a prooxidant when administered together with fructose and alone in some parameters. Our results can inspire the development of new clinical therapy in patients with MetS (Tab. 2, Ref. 34).

  20. OCDMA PON supporting ONU inter-networking based on gain-switched Fabry-Pérot lasers with external dual-wavelength injection.

    Science.gov (United States)

    Liu, Jie; Zeng, Duoduo; Guo, Changjian; Xu, Lei; He, Sailing

    2010-10-25

    We propose and demonstrate an OCDMA-PON scheme with optical network unit (ONU) internetworking capability, which utilizes low-cost gain-switched Fabry-Pérot (GS-FP) lasers with external dual-wavelength injection as the pulse sources on the ONU side. The injection-generated optical pulses in two wavelengths from the same GS-FP laser are used separately for the PON uplink transmission and ONU internetworking. Experimental results based on a two-user OCDMA system confirm the feasibility of the proposed scheme. With OCDMA technologies, separate ONU-internetworking groups can be established using different optical codes. We also give experiment results to analyze the performance of the ONU-ONU transmission at different power of interference signals when two ONU-internetworking groups are present in the OCDMA-PON.

  1. Impairment analysis of WDM-PON based on low-cost tunable lasers

    DEFF Research Database (Denmark)

    Wagner, Christoph; Eiselt, Michael H.; Lawin, Mirko

    2016-01-01

    channel must be kept below 15%. Similar values result for the upstream pilot tones. In order to limit crosstalk, such systems require reduced launch power during wavelength tuning and can cover up to 40 km differential reach. These results confirm that WDM-PON based on low-cost lasers is a technically...

  2. Photonic integrated transmitter and receiver for NG-PON2

    Science.gov (United States)

    Tavares, Ana; Lopes, Ana; Rodrigues, Cláudio; Mãocheia, Paulo; Mendes, Tiago; Brandão, Simão.; Rodrigues, Francisco; Ferreira, Ricardo; Teixeira, António

    2014-08-01

    In this paper the authors present a monolithic Photonic Integrated Circuit which includes a transmitter and a receiver for NG-PON2. With this layout it is possible to build an OLT and, by redesigning some filters, also an ONU. This technology allows reducing the losses in the transmitter and in the receiver, increasing power budget, and also reducing the OEO conversions, which has been a major problem that operators want to surpass.

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

    Science.gov (United States)

    2015-12-01

    calcium increase we further explored a potential role for calcium signaling in PON2 inactivation. Cells were treated with the calcium mobilizers ATP...which host cells are exposed. The rapid partitioning of 3OC12 into host cells and intracellular entrapment of 3OC12- acid must be considered in future

  4. Extrastriatal binding of [{sup 123}I]FP-CIT in the thalamus and pons: gender and age dependencies assessed in a European multicentre database of healthy controls

    Energy Technology Data Exchange (ETDEWEB)

    Koch, Walter; Unterrainer, Marcus; Xiong, Guoming; Bartenstein, Peter [University of Munich, Department of Nuclear Medicine, Munich (Germany); Diemling, Markus [Hermes Medical Solutions, Stockholm (Sweden); Varrone, Andrea [Karolinska University Hospital, Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm (Sweden); Dickson, John C. [UCLH NHS Foundation Trust and University College, Institute of Nuclear Medicine, London (United Kingdom); Tossici-Bolt, Livia [University Hospitals Southampton NHS Trust, Department of Medical Physics, Southampton (United Kingdom); Sera, Terez [University of Szeged, Department of Nuclear Medicine and Euromedic Szeged, Szeged (Hungary); Asenbaum, Susanne [Medical University of Vienna, Department of Neurology, Vienna (Austria); Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Centre, Amsterdam (Netherlands); Kapucu, Ozlem L. [Gazi University, Department of Nuclear Medicine, Faculty of Medicine, Ankara (Turkey); Kluge, Andreas [ABX-CRO, Dresden (Germany); Ziebell, Morten [Rigshospitalet and University of Copenhagen, Neurobiology Research Unit, Copenhagen (Denmark); Darcourt, Jacques [University of Nice-Sophia Antipolis, Nuclear Medicine Department, Centre Antoine Lacassagne, Nice (France); Nobili, Flavio [University of Genoa, Clinical Neurology Unit, Department of Neuroscience (DINOGMI), Genoa (Italy); Pagani, Marco [CNR, Institute of Cognitive Sciences and Technologies, Rome (Italy); Karolinska Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Hesse, Swen [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Leipzig University Medical Centre, Molecular Neuroimaging IFB Adiposity Diseases, Leipzig (Germany); Borght, Thierry Vander [Universite Catholique de Louvain, Nuclear Medicine Division, CHU Dinant Godinne, Yvoir (Belgium); Laere, Koen van [University Hospital and K.U. Leuven, Nuclear Medicine, Leuven (Belgium); Tatsch, Klaus [Staedtisches Klinikum Karlsruhe, Department of Nuclear Medicine, Karlsruhe (Germany); La Fougere, Christian [University of Munich, Department of Nuclear Medicine, Munich (Germany); University of Tuebingen, Department of Nuclear Medicine, Tuebingen (Germany)

    2014-10-15

    Apart from binding to the dopamine transporter (DAT), [{sup 123}I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes of interest analysis for the thalamus and the pons. Data were examined for gender and age effects as well as for potential influence of striatal DAT radiotracer binding. Thalamic binding was significantly higher than pons binding. Partial correlations showed an influence of putaminal DAT binding on measured binding in the thalamus but not on the pons. Data showed high interindividual variation in extrastriatal binding. Significant gender effects with 31 % higher binding in women than in men were observed in the thalamus, but not in the pons. An age dependency with a decline per decade (±standard error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [{sup 123}I]FP-CIT scans in healthy controls. For both the thalamus and the pons, an age-related decline in radiotracer binding was observed. Gender effects were demonstrated for binding in the thalamus only. As a potential clinical application, the data could be used as a reference to estimate SERT occupancy in addition to nigrostriatal integrity when using [{sup 123}I]FP-CIT for DAT imaging in patients treated with selective serotonin reuptake inhibitors. (orig.)

  5. Impact of PON deployment on metro networks

    Science.gov (United States)

    Poirrier, Julien; Herviou, Fabrice; Barboule, Hélène; Moignard, Maryse

    2009-01-01

    FTTH or FTTC, depending on countries and areas, will be the key technology for operators to differentiate themselves from competitors and win market share. Such a disruptive evolution of the access network should be supported by a significant re-design of the higher network layers. In the present paper, the required features of these new WDM networks are presented. Capacity and cost are the two obvious drivers. But versatility will be crucial to cope with an uncertain context (tedious prediction of traffic, regulation and services) and with very diverse population densities. Finally we also address how PON could benefit from mature WDM technologies to ease the global network design.

  6. Adaptive upstream rate adjustment by RSOA-ONU depending on different injection power of seeding light in standard-reach and long-reach PON systems

    Science.gov (United States)

    Yeh, C. H.; Chow, C. W.; Shih, F. Y.; Pan, C. L.

    2012-08-01

    The wavelength division multiplexing-time division multiplexing (WDM-TDM) passive optical network (PON) using reflective semiconductor optical amplifier (RSOA)-based colorless optical networking units (ONUs) is considered as a promising candidate for the realization of fiber-to-the-home (FTTH). And this architecture is actively considered by Industrial Technology Research Institute (ITRI) for the realization of FTTH in Taiwan. However, different fiber distances and optical components would introduce different power budgets to different ONUs in the PON. Besides, due to the aging of optical transmitter (Tx), the power decay of the distributed optical carrier from the central office (CO) could also reduce the injection power into each ONU. The situation will be more severe in the long-reach (LR) PON, which is considered as an option for the future access. In this work, we investigate a WDM-TDM PON using RSOA-based ONU for upstream data rate adjustment depending on different continuous wave (CW) injection powers. Both standard-reach (25 km) and LR (100 km) transmissions are evaluated. Moreover, a detail analysis of the upstream signal bit-error rate (BER) performances at different injection powers, upstream data rates, PON split-ratios under stand-reach and long-reach is presented.

  7. Aronia melanocarpa Treatment and Antioxidant Status in Selected Tissues in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Renata Francik

    2014-01-01

    Full Text Available Aronia juice is considered to be a source of compounds with high antioxidative potential. We conducted a study on the impact of compounds in the Aronia juice on oxidative stress in plasma and brain tissues. The influence of Aronia juice on oxidative stress parameters was tested with the use of a model with a high content of fructose and nonsaturated fats. Therefore, the activity of enzymatic (catalase, CAT, and paraoxonase, PON and nonenzymatic (thiol groups, SH, and protein carbonyl groups, PCG oxidative stress markers, which indicate changes in the carbohydrate and protein profiles, was marked in brain tissue homogenates. Adding Aronia caused statistically significant increase in the CAT activity in plasma in all tested diets, while the PON activity showed a statistically significant increase only in case of high fat diet. In animals fed with Aronia juice supplemented with carbohydrates or fat, statistically significant increase in the PON activity and the decrease in the CAT activity in brain tissue were observed. In case of the high fat diet, an increase in the number of SH groups and a decrease in the number of PCG groups in brain tissue were observed.

  8. Demonstration of digital fronthaul over self-seeded WDM-PON in commercial LTE environment.

    Science.gov (United States)

    Ma, Yiran; Xu, Zhiguang; Zhang, Chengliang; Lin, Huafeng; Wang, Qing; Zhou, Min; Wang, Heng; Yu, Jingwen; Wang, Xiaomu

    2015-05-04

    CPRI between BBU and RRU equipment is carried by self-seeded WDM-PON prototype system within commercial LTE end-to-end environment. Delay and jitter meets CPRI requirements while services demonstrated show the same performance as bare fiber.

  9. 10 Gb/s Real-Time All-VCSEL Low Complexity Coherent scheme for PONs

    DEFF Research Database (Denmark)

    Rodes Lopez, Roberto; Cheng, Ning; Jensen, Jesper Bevensee

    2012-01-01

    Real time demodulation of a 10 Gb/s all-VCSEL based coherent PON link with a simplified coherent receiver scheme is demonstrated. Receiver sensitivity of −33 dBm is achieved providing high splitting ratio and link reach....

  10. Oxidant-antioxidant status in Egyptian children with sickle cell anemia: a single center based study

    Directory of Open Access Journals (Sweden)

    Mona Kamal El-Ghamrawy

    Full Text Available OBJECTIVE:the present study was conducted to investigate the oxidant-antioxidant status in Egyptian children with sickle cell anemia.METHODS:the serum levels of total antioxidant capacity (TAO, paraoxonase (PON, vitamin E, nitrite, and malondialdehyde (MDA were measured in 40 steady state children with homozygous sickle cell anemia (24 males and 16 females and 20 apparently healthy age- and gender-matched controls.RESULTS:mean serum TAO, PON, vitamin E, and nitrite levels were significantly lower in the group with sickle cell anemia, whereas mean serum MDA was significantly higher in these children compared to controls. No significant differences in mean levels of TAO, PON, nitrite, vitamin E, and MDA were found in sickle cell anemia patients receiving hydroxyurea when compared with those not receiving hydroxyurea. A significant negative correlation between serum nitrite and the occurrence of vaso-occlusive crises (VOC was observed (r = -0.3, p = 0.04. PON level was found to be positively correlated with patients' weight and BMI (r = -0.4, p = 0.01; r = -0.7, p < 0.001, respectively, but not with frequency of VOC. The area under the curve of serum nitrite in predicting occurrence of VOC was 0.782, versus 0.701 for PON, and 0.650 for TAO (p = 0.006. Serum MDA was not correlated with nitrite, PON, TAO, or vitamin E levels. No significant correlations were detected between serum nitrite and hemoglobin or antioxidant enzymes.CONCLUSION:children with sickle cell anemia have chronic oxidative stress that may result in increased VOC, and decreased serum nitrite may be associated with increases in VOC frequency. A novel finding in this study is the decrease in PON level in these patients, which is an interesting subject for further research.

  11. Advanced glycation end products affect cholesterol homeostasis by impairing ABCA1 expression on macrophages.

    Science.gov (United States)

    Kamtchueng Simo, Olivier; Ikhlef, Souade; Berrougui, Hicham; Khalil, Abdelouahed

    2017-08-01

    Reverse cholesterol transport (RCT), which is intimately linked to high-density lipoproteins (HDLs), plays a key role in cholesterol homeostasis and the prevention of atherosclerosis. The goal of the present study was to investigate the effect of aging and advanced glycation end products (AGEs) on RCT as well as on other factors that may affect the antiatherogenic property of HDLs. The transfer of macrophage-derived cholesterol to the plasma and liver and then to the feces for elimination was significantly lower in aged mice than in young mice. Chronic injection of d -galactose (D-gal) or AGEs also significantly reduced RCT (65.3% reduction in [ 3 H]cholesterol levels in the plasma of D-gal-treated mice after 48 h compared with control mice, P cholesterol levels in the plasma, although the levels were lower than those of control mice. The in vitro incubation of HDLs with dicarbonyl compounds increased the carbonyl and conjugated diene content of HDLs and significantly reduced PON1 paraoxonase activity (87.4% lower than control HDLs, P cholesterol (69.1% decrease, P < 0.0001). Our results showed, for the first time, that RCT is altered with aging and that AGEs contribute significantly to this alteration.

  12. [Alterations in the protein content and dysfunction of high-density lipoproteins from hyperhomocysteinemic mice].

    Science.gov (United States)

    Julve, Josep; Errico, Teresa Laura; Chen, Xiangyu; Santos, David; Freixa, Júlia; Porcel, Inmaculada; Cubero, Esther; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2013-01-01

    The aim of this study was to evaluate the proteic changes in high-density lipoproteins (HDL) induced by methionine-induced hyperhomocysteinemia in mice and its relationship with two of their main antiatherogenic properties. The oral administration of methionine resulted in an elevation (~8 times) in the plasma concentration of homocysteine. Hyperhomocysteinemia was inversely correlated with the plasma concentration of HDL cholesterol and its main protein component of HDL, apolipoprotein (apo) A-I, respectively. The cholesterol efflux in vivo from macrophages to HDL was decreased in hyperhomocysteinemic mice compared with the control mice. However, the reverse cholesterol transport from macrophages to feces remained unchanged. On the other hand, the ability of HDL from hyperhomocysteinemic mice to prevent the oxidative modification of low-density lipoproteins (LDL) was found decreased and associated with a concomitant reduction in the plasma activity of paraoxonase-1 (PON1) and the plasma concentration of apoA-I, and with a relative reduction in the apoA-IV content (~1.5 times) in the hyperhomocysteinemic HDL, respectively. The decrease in the ability of HDL from hyperhomocysteinemic mice to prevent LDL from oxidation was associated with a decrease in the apoA-I, PON1 and apoA-IV. Copyright © 2013 Elsevier España, S.L. and SEA. All rights reserved.

  13. 300 Gb/s IM/DD based SDM-WDM-PON with laserless ONUs

    DEFF Research Database (Denmark)

    Bao, Fangdi; Morioka, Toshio; Oxenløwe, Leif Katsuo

    2018-01-01

    A low-cost, high-speed SDM-WDM-PON architecture is proposed by using a multi-core fiber (MCF) and intensity modulation/directly detection (IM/DD). One of the MCF cores is used for sending laser sources from optical line terminal (OLT) to optical network unit (ONU), thus facilitating laserless...

  14. Experimental demonstration of novel source-free ONUs in bidirectional RF up-converted optical OFDM-PON utilizing polarization multiplexing.

    Science.gov (United States)

    Zhang, Chongfu; Chen, Chen; Feng, Yuan; Qiu, Kun

    2012-03-12

    We propose and experimentally demonstrate a novel cost-effective optical orthogonal frequency-division multiplexing-based passive optical network (OFDM-PON) system, wherein all optical network units (ONUs) are source-free not only in the optical domain but also in the electric domain, by utilizing polarization multiplexing (PolMUX) in the downlink transmission. Two pure optical bands with a frequency interval of 10 GHz and downlink up-converted 10 GHz OFDM signal are carried in two orthogonal states of polarization (SOPs), respectively. 10 GHz radio frequency (RF) source can be generated by a heterodyne of two pure optical bands after polarization beam splitting in each ONU, therefore it can be used to down-convert the downlink OFDM signal and up-convert the uplink OFDM signal. In the whole bidirectional up-converted OFDM-PON system, only one single RF source is employed in the optical line terminal (OLT). Experimental results successfully verify the feasibility of our proposed cost-effective optical OFDM-PON system.

  15. Asymptomatic pons tuberculoma in an infant with miliary tuberculosis

    International Nuclear Information System (INIS)

    Uysal, Gulnar; Guven, Akif; Gursoy, Tugba; Altunc, Umut

    2005-01-01

    Miliary tuberculosis is caused by the hematogenous spread of Mycobacterium tuberculosis and consists of 1.5% of all tuberculosis cases. It is seen mostly in infants because of the immature immune system, and central nervous system CNS involvement is not rare. Tuberculomas are rarely seen in the localized form of CNS tuberculosis, and only 4% are localized in the brain stem. We report a 4.5-month-old infant who deteriorated during follow-up with the diagnosis of cytomegalovirus pneumonia, and afterwards received the diagnosis of miliary tuberculosis. Although the baby had no neurologic abnormality and cerebrospinal fluid findings were normal, cranial MRI revealed contrast enhanced nodular lesions in pons, cerebellum, and right parietal region. The case is presented to intensify the importance of CNS investigation even if the patient with miliary tuberculosis has no neurologic finding. (author)

  16. A New Wavelength Optimization and Energy-Saving Scheme Based on Network Coding in Software-Defined WDM-PON Networks

    Science.gov (United States)

    Ren, Danping; Wu, Shanshan; Zhang, Lijing

    2016-09-01

    In view of the characteristics of the global control and flexible monitor of software-defined networks (SDN), we proposes a new optical access network architecture dedicated to Wavelength Division Multiplexing-Passive Optical Network (WDM-PON) systems based on SDN. The network coding (NC) technology is also applied into this architecture to enhance the utilization of wavelength resource and reduce the costs of light source. Simulation results show that this scheme can optimize the throughput of the WDM-PON network, greatly reduce the system time delay and energy consumption.

  17. A reconfigurable all-optical VPN based on XGM effect of SOA in WDM PON

    Science.gov (United States)

    Hu, Xiaofeng; Zhang, Liang; Cao, Pan; Wang, Tao; Su, Yikai

    2010-12-01

    We propose and experimentally demonstrate a reconfigurable all-optical VPN scheme enabling intercommunications among different ONUs in a WDM PON. Reconfiguration is realized by dynamically setting wavelength conversion of optical VPN signal using a SOA in the OLT.

  18. Senyalització a baixa potència a TWDM-PON

    OpenAIRE

    Peso Estébanez, Patricia

    2015-01-01

    Treball realitzat al Istituto Superiore Mario Boella (ISMB) [ANGLÈS] Nowadays the demand for high transmission velocities brings the opportunity to deeply study the usage of optical networks, which present high bit rates moreover large distance budgets on the link. New standard on the Passive Optical Networks, NG-PON2, is on the standardization process. This standard increase both the bit rates on downstream and upstream communications, the number of users connected to one Central Office (...

  19. 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.

  20. Isolated pons involvement in Posterior Reversible Encephalopathy Syndrome: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Mariangela Ferrara

    2017-03-01

    Conclusions: Though isolated infratentorial involvement in PRES recognizes several causes, hypertension, which is a common feature in Turner syndrome, would have played a key role in our case with solely pons MRI T2-hyperintensity.

  1. Immediate IPTV channel leave by explicit user tracking in PON

    Science.gov (United States)

    Zhu, Peng; Yoshiuchi, Hideya; Yoshizawa, Satoshi

    2007-11-01

    In this paper, we propose a novel IPTV channel leave mechanism for Passive Optical Network (PON). By explicit user tracking and automatic differentiation of IGMP v2 and v3 users, the proposed mechanism can realize immediate channel leave in both Optical Line Terminal (OLT) and Optical Network Unit (ONU) while avoiding removing the channel which still has users. Simulation results show that the proposed mechanism can significantly save the bandwidth consumption during "channel surf" by users, compared to the standard IGMP timeout mechanism.

  2. Remote heterodyne millimeter-wave over fiber based OFDM-PON with master-to-slave injected dual-mode colorless FPLD pair.

    Science.gov (United States)

    Chen, Hsiang-Yu; Chi, Yu-Chieh; Lin, Gong-Ru

    2015-08-24

    A remote heterodyne millimeter-wave (MMW) carrier at 47.7 GHz over fiber synthesized with the master-to-slave injected dual-mode colorless FPLD pair is proposed, which enables the future connection between the wired fiber-optic 64-QAM OFDM-PON at 24 Gb/s with the MMW 4-QAM OFDM wireless network at 2 Gb/s. Both the single- and dual-mode master-to-slave injection-locked colorless FPLD pairs are compared to optimize the proposed 64-QAM OFDM-PON. For the unamplified single-mode master, the slave colorless FPLD successfully performs the 64-QAM OFDM data at 24 Gb/s with EVM, SNR and BER of 8.5%, 21.5 dB and 2.9 × 10(-3), respectively. In contrast, the dual-mode master-to-slave injection-locked colorless FPLD pair with amplified and unfiltered master can transmit 64-QAM OFDM data at 18 Gb/s over 25-km SMF to provide EVM, SNR and BER of 8.2%, 21.8 dB and 2.2 × 10(-3), respectively. For the dual-mode master-to-slave injection-locked colorless FPLD pair, even though the modal dispersion occurred during 25-km SMF transmission makes it sacrifice the usable OFDM bandwidth by only 1 GHz, which guarantees the sufficient encoding bitrate for the optically generated MMW carrier to implement the fusion of MMW wireless LAN and DWDM-PON with cost-effective and compact architecture. As a result, the 47.7-GHz MMW carrier remotely beat from the dual-mode master-to-slave injection-locked colorless FPLD pair exhibits an extremely narrow bandwidth of only 0.48 MHz. After frequency down-conversion operation, the 47.7-GHz MMW carrier successfully delivers 4-QAM OFDM data up to 2 Gb/s with EVM, SNR and BER of 33.5%, 9.51 dB and 1.4 × 10(-3), respectively.

  3. Impairments due to Burst-Mode Transmission in a Raman-based Long Reach PON Link

    DEFF Research Database (Denmark)

    Kjær, Rasmus; Tafur Monroy, Idelfonso; Oxenløwe, Leif Katsuo

    2007-01-01

    A recently proposed passive-optical-network (PON) link based on distributed Raman amplification is tested with disturbing burst-mode traffic. The resulting impairments are quantified through penalty measurements on a single surviving data channel as a function of the disturbing channel power. When...... the disturbing channels co- or counter propagate with the data channel, penalties of less than 1 dB are found for disturbing input powers up to 7 and 11 dBm, respectively. The penalty is further reduced when a moderate amount of continuous-wave light is used to clamp the gain. The results indicate...

  4. Changes in orexinergic immunoreactivity of the piglet hypothalamus and pons after exposure to chronic postnatal nicotine and intermittent hypercapnic hypoxia.

    Science.gov (United States)

    Hunt, Nicholas J; Russell, Benjamin; Du, Man K; Waters, Karen A; Machaalani, Rita

    2016-06-01

    We recently showed that orexin expression in sudden infant death syndrome (SIDS) infants was reduced by 21% in the hypothalamus and by 40-50% in the pons as compared with controls. Orexin maintains wakefulness/sleeping states, arousal, and rapid eye movement sleep, abnormalities of which have been reported in SIDS. This study examined the effects of two prominent risk factors for SIDS, intermittent hypercapnic hypoxia (IHH) (prone-sleeping) and chronic nicotine exposure (cigarette-smoking), on orexin A (OxA) and orexin B (OxB) expression in piglets. Piglets were randomly assigned to five groups: saline control (n = 7), air control (n = 7), nicotine [2 mg/kg per day (14 days)] (n = 7), IHH (6 min of 7% O2 /8% CO2 alternating with 6-min periods of breathing air, for four cycles) (n = 7), and the combination of nicotine and IHH (N + IHH) (n = 7). OxA/OxB expression was quantified in the central tuberal hypothalamus [dorsal medial hypothalamus (DMH), perifornical area (PeF), and lateral hypothalamus], and the dorsal raphe, locus coeruleus of the pons. Nicotine and N + IHH exposures significantly increased: (i) orexin expression in the hypothalamus and pons; and (ii) the total number of neurons in the DMH and PeF. IHH decreased orexin expression in the hypothalamus and pons without changing neuronal numbers. Linear relationships existed between the percentage of orexin-positive neurons and the area of pontine orexin immunoreactivity of control and exposure piglets. These results demonstrate that postnatal nicotine exposure increases the proportion of orexin-positive neurons in the hypothalamus and fibre expression in the pons, and that IHH exposure does not prevent the nicotine-induced increase. Thus, although both nicotine and IHH are risk factors for SIDS, it appears they have opposing effects on OxA and OxB expression, with the IHH exposure closely mimicking what we recently found in SIDS. © 2016 Federation of European Neuroscience Societies and John

  5. Optical power equalization for upstream traffic with injection-locked Fabry-Perot lasers in TDM-PON

    Science.gov (United States)

    Huang, Ting-Tsan; Sheu, Lih-Gen; Chi, Sien

    2010-10-01

    An optical power equalization of upstream traffic in time-division-multiplexed passive optical network (TDM-PON) based on injection-locked Fabry-Perot lasers has been experimentally investigated. The upstream transmitters with stable spectrum are achieved by using an external injection light source in the optical line terminal (OLT). The different upstream powers can be equalized by injection locking a Fabry-Perot laser diode (FP-LD) biased below threshold current in OLT. The dynamic upstream power range from - 8.5 to - 19.5 db m is reduced to a 1.6 dB maximal power variation, when the uplink signal is directly modulated at 1.25 Gb/s.

  6. Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers

    Directory of Open Access Journals (Sweden)

    Ravi Varatharajalu

    2016-01-01

    Full Text Available Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories from ω-3 polyunsaturated fatty acids (PUFA and Lieber-deCarli high menhaden (13.8% of total calories from ω-3 PUFA alcohol-liquid (5% diets supplemented with or without curcumin (150 mg/kg/day for 8 weeks. Treatment with curcumin protected against high ω-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1 mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to high ω-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol-induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with high ω-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and high ω-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis.

  7. Effect of rosuvastatin on fasting and postprandial endothelial biomarker levels and microvascular reactivity in patients with type 2 diabetes and dyslipidemia: a preliminary report.

    Science.gov (United States)

    Kim, Kyoung Min; Jung, Kyong Yeun; Yun, Han Mi; Lee, Seo Young; Oh, Tae Jung; Jang, Hak Chul; Lim, Soo

    2017-11-09

    The cardiovascular benefits of statins have been proven, but their effect on circulation in small vessels has not been examined fully. We investigated the effect of 20 mg rosuvastatin on biomarkers, including paraoxonase-1 (PON-1) and asymmetric dimethylarginine (ADMA), and on microvascular reactivity. We enrolled 20 dyslipidemic patients with type 2 diabetes and 20 age- and body mass index (BMI)-matched healthy controls. Rosuvastatin (20 mg/day) was given to the patient group for 12 weeks. Biochemical parameters, including PON-1 and ADMA, were compared between the patient and control groups, and before and after rosuvastatin treatment in the patient group. Fasting and 2 h postprandial levels of PON-1 and ADMA after mixed-meal challenge were also compared. Microvascular reactivity in a peripheral artery was examined using laser Doppler flowmetry. The respective mean ± standard deviation of age and BMI were 50.1 ± 3.8 year and 25.8 ± 3.7 kg/m 2 in the patients and 50.2 ± 3.2 year and 25.4 ± 3.4 kg/m 2 in the controls. The patient group had worse profiles of cardiometabolic biomarkers, including PON-1 and ADMA, than the controls. In the patients treated with 20 mg rosuvastatin, low-density lipoprotein (LDL)-cholesterol decreased from 147.2 ± 26.5 to 68.3 ± 24.5 mg/dL and high-density lipoprotein (HDL)-cholesterol increased from 42.4 ± 5.2 to 44.7 ± 6.2 mg/dL (both P fasting and 2 h postprandial levels of PON-1 increased and those of ADMA decreased after treatment with rosuvastatin for 12 weeks. The changes in postprandial levels of both biomarkers were greater than those after fasting. Microcirculation assessed as reactive hyperemia in the patients after an ischemic challenge increased significantly from 335.3 ± 123.4 to 402.7 ± 133.4% after rosuvastatin treatment. The postprandial changes in the biomarkers were significantly associated with improvement of microvascular reactivity. Rosuvastatin treatment for 12

  8. Expression of Membrane-Bound Human AminopeptidaseP as a Soluble Enzyme and an Investigation into Its Efficacy Towards Offering Protection Against the Toxicity of Chemical Warfare Nerve Agents

    Science.gov (United States)

    2016-09-01

    APP appears to be the cleavage of an N-terminal amino acid residue from peptides exhibiting a proline at P-1 residue such as bradykinin [11]. In...amino acid residue 658, replacing the Trp codon (TGG) immediately upstream of the hydrophobic peptide acting as the GPI-anchoring signal. A 6...hydrolase activity between human and chimeric recombinant mammalian paraoxonase-1 enzymes. Biochemistry, 2009. 48(43): p. 10416-22. 19. Aleti, V., et al

  9. Design of the frame structure for a multiservice interactive system using ATM-PON

    Science.gov (United States)

    Nam, Jae-Hyun; Jang, Jongwook; Lee, Jung-Tae

    1998-10-01

    The MAC (Medium Access Control) protocol controls B-NT1s' (Optical Network Unit) access to the shared capacity on the PON, this protocol is very important if TDMA (Time Division Multiple Access) multiplexing is used on the upstream. To control the upstream traffic some kind of access protocol has to be implemented. There are roughly two different approaches to use request cells: in a collision free way or such that collisions in a request slot are allowed. It is the objective of this paper to describe a MAC-protocol structure that supports both approaches and hybrids of it. In our paper we grantee the QoS (Quality of Service) of each B-NT1 through LOC, LOV, LOA field that are the length field of the transmitted cell at each B-NT1. Each B-NT1 transmits its status of request on request cell.

  10. PAM4 based symmetrical 112-Gbps long-reach TWDM-PON

    Science.gov (United States)

    Wu, Liyu; Gao, Fan; Zhang, Minming; Fu, Songnian; Deng, Lei; Choi, Michael; Chang, Donald; Lei, Gordon K. P.; Liu, Deming

    2018-02-01

    We experimentally demonstrate cost effective symmetrical 112-Gbps long-reach passive optical network (LR-PON) over 70-km standard signal mode fiber (SSMF), based on pulse amplitude modulation (PAM)-4. Four 10G-class directly modulated lasers (DMLs) at C-band are used for achieving 4 × 28-Gbps downstream transmission, while two 18G-class DMLs at O-band are used to realize 2 × 56-Gbps upstream transmission, without any optical amplification in optical distributed network (ODN). Both dispersion compensation fiber (DCF) for downstream signal and praseodymium-doped fiber amplifier (PDFA) for upstream signal are equipped at optical line terminal (OLT). Meanwhile, sparse Volterra filter (SVF) equalizer is proposed to mitigate the transmission impairments with substantial reduction of computation complexity. Finally, we can successfully provide a loss budget of 33 dB per downstream wavelength channel, indicating of 64 optical network units (ONUs) with more than 1.25 Gbps per ONU.

  11. Hypertensive Encephalopathy: Isolated Pons Involvement Mimicking Central Pontine Myelinolysis

    International Nuclear Information System (INIS)

    Gamanagatti, S.; Subramanian, S.

    2006-01-01

    MRI of the brain was performed, and it demonstrated an isolated high signal on the T2 weighted and fluid attenuated inversion recovery sequences that involved only the central pons with sparing the periphery. There was no restricted diffusion on diffusion weighted imaging. The differential diagnosis included posterior reversible syndrome and central pontine myelinolysis; however, the blood sodium on admission was normal. The pathogenesis of HE is that the auto-regulatory mechanisms that control the cerebral blood flow are exceeded, resulting in hyper-perfusion. The consequent over-distension of the cerebral vessels, the breakdown of the blood brain barrier and ultimately, the extravasation of fluid into the interstitium all cause vasogenic edema. In most cases, the changes of hypertensive encephalopathy represent reversible vasogenic edema, which can be seen on T2-weighted images, and restricted diffusion is not seen on the diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) maps. Hypertensive encephalopathy that manifests as a reversible increased signal isolated to the pons on T2-weighted images is extremely uncommon. The differential diagnosis for such pontine T2 hyperintensity includes pontine glioma, ischemic and radiation changes (generally irreversible conditions), as well as central pontine myelinolysis (CPM) and demyelinating disorders such as multiple sclerosis, acute disseminated encephalomyelitis and rhomb-encephalitis. In CPM electrolyte imbalances provide a clue for the diagnosis, where as for glioma, there will be an expansion and mass effect. In conclusion, clinical recognition of brainstem HE may be difficult. The features of a lack of correlation between the severity of the radiological abnormality and the clinical status, combined with the rapid resolution following antihypertensive treatment, should suggest the diagnosis. It is important for the radiologist to be familiar with the imaging abnormalities of this life

  12. Hypertensive Encephalopathy: Isolated Pons Involvement Mimicking Central Pontine Myelinolysis

    Energy Technology Data Exchange (ETDEWEB)

    Gamanagatti, S.; Subramanian, S. [India Institute of Medical Sciences, New Delhi (India)

    2006-09-15

    MRI of the brain was performed, and it demonstrated an isolated high signal on the T2 weighted and fluid attenuated inversion recovery sequences that involved only the central pons with sparing the periphery. There was no restricted diffusion on diffusion weighted imaging. The differential diagnosis included posterior reversible syndrome and central pontine myelinolysis; however, the blood sodium on admission was normal. The pathogenesis of HE is that the auto-regulatory mechanisms that control the cerebral blood flow are exceeded, resulting in hyper-perfusion. The consequent over-distension of the cerebral vessels, the breakdown of the blood brain barrier and ultimately, the extravasation of fluid into the interstitium all cause vasogenic edema. In most cases, the changes of hypertensive encephalopathy represent reversible vasogenic edema, which can be seen on T2-weighted images, and restricted diffusion is not seen on the diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) maps. Hypertensive encephalopathy that manifests as a reversible increased signal isolated to the pons on T2-weighted images is extremely uncommon. The differential diagnosis for such pontine T2 hyperintensity includes pontine glioma, ischemic and radiation changes (generally irreversible conditions), as well as central pontine myelinolysis (CPM) and demyelinating disorders such as multiple sclerosis, acute disseminated encephalomyelitis and rhomb-encephalitis. In CPM electrolyte imbalances provide a clue for the diagnosis, where as for glioma, there will be an expansion and mass effect. In conclusion, clinical recognition of brainstem HE may be difficult. The features of a lack of correlation between the severity of the radiological abnormality and the clinical status, combined with the rapid resolution following antihypertensive treatment, should suggest the diagnosis. It is important for the radiologist to be familiar with the imaging abnormalities of this life

  13. Radiation necrosis of the optic chiasm, optic tract, hypothalamus, and upper pons after radiotherapy for pituitary adenoma, detected by gadolinium-enhanced, T1-weighted magnetic resonance imaging: Case report

    International Nuclear Information System (INIS)

    Tachibana, O.; Yamaguchi, N.; Yamashima, T.; Yamashita, J.

    1990-01-01

    A 26-year-old woman was treated for a prolactin secreting pituitary adenoma by surgery and radiotherapy (5860 rads). Fourteen months later, she developed right hemiparesis and dysarthria. A T1-weighted magnetic resonance imaging scan using gadolinium contrast showed a small, enhanced lesion in the upper pons. Seven months later, she had a sudden onset of loss of vision, and radiation optic neuropathy was diagnosed. A T1-weighted magnetic resonance imaging scan showed widespread gadolinium-enhanced lesions in the optic chiasm, optic tract, and hypothalamus. Magnetic resonance imaging is indispensable for the early diagnosis of radiation necrosis, which is not visualized by radiography or computed tomography

  14. A cost-effective structure of a centralized-light-source WDM-PON utilizing inverse-duobinary-RZ downstream and DPSK upstream

    International Nuclear Information System (INIS)

    Chen Long-Quan; Qiao Yao-Jun; Ji Yue-Feng

    2013-01-01

    In this paper, we propose a new structure of a centralized-light-source wavelength division multiplexed passive optical network (WDM-PON) utilizing inverse-duobinary-return-to-zero (inverse-duobinary-RZ) downstream and DPSK upstream. It reuses downstream light for the upstream modulation, which retrenches lasers assembled at each optical network unit (ONU), and ultimately cuts down the cost of ONUs a great deal. Meanwhile, a 50-km-reach WDM-PON experiment with 10-Gb/s inverse-duobinary-RZ downstream and 6-Gb/s DPSK upstream is demonstrated here. It is revealed to be a novel cost-effective alternative for the next generation access network. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

  15. POlish-Norwegian Study (PONS): research on chronic non-communicable diseases in European high risk countries - study design.

    Science.gov (United States)

    Zatoński, Witold A; Mańczuk, Marta

    2011-01-01

    A large-scale population study of health and disease would represent the most powerful tool to address these important issues in Poland. The aim is to extensively survey the study population with respect to important factors related to health and wellbeing, and subsequently, the intention is to follow-up the population for important health outcomes, including the incidence and mortality of cancer, cardiovascular disease, and other major causes of morbidity and mortality. The infrastructure for establishing a large cohort of people in Poland is needed; therefore, the PONS (Polish-Norwegian Study) project represents an eff ort to establish such infrastructure. The PONS Study is enrolling individuals aged 45-64 years. Structured lifestyle and food frequency questionnaires are administered. Study participants undergo medical check-up, anthropometric measurements and provide blood and urine sample for long-term storage. Fasting glucose and lipids profile are checked in the laboratory. This report describes the design, justification and methodology of the presented prospective cohort study. Recruitment of participants began in September 2010, and by the end of 2011 it is planned to achieve a total of between 10,000 – 15,000 participants. The PONS study is the fi rst prospective cohort study with blood and urine collection ever conducted in Central and Eastern Europe. It will provide reliable new data on both established and emerging risk factors for several major chronic diseases in a range of different circumstances.

  16. 85 km long reach PON system using a reflective SOA-EA modulator and distributed Raman fiber amplification

    NARCIS (Netherlands)

    Tafur Monroy, I.; Öhman, F.; Yvind, K.; Kjaer, R.; Peucheret, C.; Koonen, A.M.J.; Jeppesen, P.

    2006-01-01

    We report on a bidirectional 85 km long reach PON system supported by distributed fiber Raman amplification with a record 7.5 Gb/s remote carrier modulated upstream signal by employing a reflective SOA-EA monolithically integrated circuit.

  17. Activated neuro-oxidative and neuro-nitrosative pathways at the end of term are associated with inflammation and physio-somatic and depression symptoms, while predicting outcome characteristics in mother and baby.

    Science.gov (United States)

    Roomruangwong, Chutima; Barbosa, Decio Sabbatini; Matsumoto, Andressa Keiko; Nogueira, André de Souza; Kanchanatawan, Buranee; Sirivichayakul, Sunee; Carvalho, André F; Duleu, Sebastien; Geffard, Michel; Moreira, Estefania Gastaldello; Maes, Michael

    2017-12-01

    To examine oxidative & nitrosative stress (O&NS) biomarkers at the end of term in relation to perinatal affective symptoms, neuro-immune biomarkers and pregnancy-related outcome variables. We measured plasma advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical trapping antioxidant parameter (TRAP), -sulfhydryl (-SH), peroxides (LOOH) and paraoxonase (PON)1 activity in pregnant women with and without prenatal depression and non-pregnant controls. Pregnancy is accompanied by significantly increased AOPP and NOx, and lowered TRAP, -SH and LOOH. Increased O&NS and lowered LOOH and -SH levels are associated with prenatal depressive and physio-somatic symptoms (fatigue, pain, dyspepsia, gastro-intestinal symptoms). Increased AOPP and NOx are significantly associated with lowered -SH, TRAP and zinc, and with increased haptoglobin and C-reactive protein levels. Increased O&NS and lowered TRAP and PON 1 activity, at the end of term predict mother (e.g. hyperpigmentation, labor duration, caesarian section, cord length, breast milk flow) and baby (e.g. sleep and feeding problems) outcome characteristics. Pregnancy is accompanied by interrelated signs of O&NS, lowered antioxidant defenses and activated neuro-immune pathways. Increased O&NS at the end of term is associated with perinatal depressive and physio-somatic symptoms and may predict obstetric and behavioral complications in mother and baby. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 2x2 MIMO-OFDM Gigabit fiber-wireless access system based on polarization division multiplexed WDM-PON

    DEFF Research Database (Denmark)

    Deng, Lei; Pang, Xiaodan; Zhao, Ying

    2012-01-01

    We propose a spectral efficient radio over wavelength division multiplexed passive optical network (WDM-PON) system by combining optical polarization division multiplexing (PDM) and wireless multiple input multiple output (MIMO) spatial multiplexing techniques. In our experiment, a training-based...

  19. 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

  20. Oxidative profiles of LDL and HDL isolated from women with preeclampsia.

    Science.gov (United States)

    León-Reyes, G; Maida-Claros, R F; Urrutia-Medina, A X; Jorge-Galarza, E; Guzmán-Grenfell, A M; Fuentes-García, S; Medina-Navarro, R; Moreno-Eutimio, M A; Muñoz-Sánchez, J L; Hicks, J J; Torres-Ramos, Y D

    2017-05-16

    Oxidative stress causes biochemical changes in lipids and proteins; these changes can induce damage to the vascular endothelium and create maternal complications that are characteristic of preeclampsia. In this study, we evaluated the oxidative profile of lipoproteins isolated from women with preeclampsia. Thirty women diagnosed with preeclampsia and thirty women without preeclampsia were included in the study. Lipid-damage biomarkers, including conjugated dienes, lipohydroperoxides and malondialdehyde, were measured. The reduction of nitroblue tetrazolium, the formation of dityrosines, and the carbonylation of proteins were assessed as indicators of protein damage. The protective activity of HDL-c was evaluated by the paraoxonase-I activity present on the HDL-c particles. Serum lipid profiles were also quantified in both groups. Data were analysed using Student's t test and the Pearson correlation coefficient. Our results demonstrated in PE women evident oxidative changes in the lipids and proteins in HDL-c and LDL-c particles and the activity of the antioxidant enzyme PON-I decreased 59.9%. HDL-c exhibited self-defence, as demonstrated by the negative correlation between paraoxonase-I activity and the formation of lipohydroperoxides in HDL-c (r = -0.3755, p preeclampsia show oxidative damage to lipids and proteins. We propose an oxidative profile based on the oxidation levels indicated by each of the markers used. We also found that paraoxonase-I is inactivated in the presence of lipohydroperoxides. Antioxidant support might be helpful to reduce oxidative stress in patients with preeclampsia. Further investigations are necessary to define the association between antioxidant activities and preeclampsia.

  1. PONS - Mobility Assistance on Footpaths for Public Transportation.

    Science.gov (United States)

    Koutny, Reinhard; Miesenberger, Klaus

    2015-01-01

    This paper presents an ongoing project targeting mobility support for users of public transportation including people with limited mobility. Existing approaches in this field mostly offer non-continuous guidance during the whole journey including multiple rides with different vehicles and footpaths in between at transfer points. Especially people with limited mobility, like people with disabilities and elderly people, or travelers who are not familiar with the specific route or transfer point, like tourists, often struggle with public transportation. They crave for a seamless approach covering all links of the mobility chain - the sequence of sections of the whole route - and providing comprehensive assistance throughout the whole journey. Previous projects and widespread experiences of project partners revealed that especially footpath sections are lacking proper support. In particular, the consortium identified three problem areas in existing approaches when dealing with footpath sections: (1) A lack of information, (2) a lack of orientation and (3) a lack of provision of services. In order to bridge (lat. PONS) these gaps in the mobility chain, new paradigms and technology concepts are developed to tackle the shortcomings on footpaths and combined in a toolkit to help developers of applications with focus on pedestrian navigation and public transport to improve their solutions with sustainable and state-of-the-art approaches.

  2. Power budget improvement of symmetric 40 Gb/s TWDM based PON2 system utilizing DMLs and DCF technique

    Science.gov (United States)

    Bindhaiq, Salem; Zulkifli, Nadiatulhuda; Supa'at, Abu Sahmah M.; Idrus, Sevia M.; Salleh, M. S.

    2018-01-01

    In this paper, we propose to use optical dispersion compensation based on the widely deployed compensating fiber (DCF) employing directly modulated lasers (DMLs) to improve the power budget in a symmetric 40 Gb/s time and wavelength division multiplexed-passive optical network (TWDM-PON) systems. The DML output waveforms in terms of output optical power, bandwidth enhancement factor (α) characteristics are investigated in order to minimize the effect of DML chirp and improve the transmission performance. Simulation results show dispersion compensation of up to 140 km of SMF with power budget of 56.6 dB and less than 2 dB dispersion penalty. The feasibility of bandwidth enhancement factor and power budget is also investigated. The simulation results indicate sufficient dispersion compensation for TWDM-PON based on DML transmission, which may vary considerably in their practical demonstration due to different system characterization.

  3. The radio-on-fiber-wavelength-division-multiplexed-passive-optical network (WDM-RoF-PON) for wireless and wire layout with linearly-polarized dual-wavelength fiber laser and carrier reusing

    Science.gov (United States)

    Ji, Wei; Chang, Jun

    2013-07-01

    In this paper, we design a WDM-RoF-PON based on linearly-polarized dual-wavelength fiber laser and CSRZ-DPSK, which can achieve wire-line and wireless access synchronously. With the CSRZ-DPSK modulation, the wireless access in ONU can save RF source and the frequency of radio carrier can be controlled by OLT. The dual-wavelength fiber laser is the union light source of WDM-PON with polarization multiplexing. By the RSOA and downstream light source reusing, the ONU can save omit laser source and makes the WDM-PON to be colorless. The networking has the credible transmission property, including wireless access and fiber transmission. The networking also has excellent covering range.

  4. Adaptación española de la versión reducida multicanal del Perfil de Sensibilidad No Verbal (MiniPONS

    Directory of Open Access Journals (Sweden)

    Francisco Martínez-Sánchez

    2013-05-01

    Full Text Available En este trabajo se presenta la adaptación española de la versión reducida multicanal del Perfil de Sensibilidad No Verbal (MiniPONS (Bänziger, Scherer, Hall y Rosenthal, 2011. Esta escala evalúa las diferencias individuales en la habilidad para reconocer emociones, actitudes interpersonales y comunicación de intenciones por canales no verbales. Esta versión multicanal reducida está compuesta por 64 estímulos no verbales de vídeo y/o audio que representan a una mujer en blanco y negro. El principal objetivo de este estudio es analizar las propiedades psicométricas del MiniPONS empleando para ello una amplia muestra de participantes (N = 1154 de entre 18 a 60 años, también se examinaron las diferencias en la sensibilidad no verbal en función del sexo y la edad. Se presentan los valores normativos, la fiabilidad y validez en tres estudios con 168, 254 y 1154 estudiantes universitarios. Los resultados muestran que las mujeres obtienen mejores puntuaciones en todas las condiciones estimulares, éstas no sólo procesan más eficientemente información emocional no verbal por canales unisensoriales (rostro, cuerpo, voz, si no que también la integran mejor. Los resultados indican que la versión española del MiniPONS presenta unas propiedades psicométricas similares a la escala original, mostrando moderada consistencia interna y fiabilidad test-retest, así como también una razonable validez convergente obtenida en las correlaciones con otras pruebas que evalúan la capacidad de reconocimiento emocional. Se concluye que la versión española del MiniPONS es un instrumento que evalúa adecuadamente la sensibilidad no verbal. Se discuten las limitaciones y potencial utilidad de la escala.

  5. The Neuroprotective Effect of Cornus mas on Brain Tissue of Wistar Rats

    Directory of Open Access Journals (Sweden)

    Renata Francik

    2014-01-01

    Full Text Available Cornelian cherry (Cornus mas is a valuable source of phenolic antioxidants. Flavonoid derivatives as nonenzymatic antioxidants are important in the pathophysiology of many diseases including neurological disorders (e.g., Alzheimer’s disease or heart disease. In this study, we examined the effect of an addition of freeze-dried fruit of cornelian cherry on three types of diets: control diet, fructose diet, and diet enriched in fats (high-fat diet. This effect was studied by determining the following antioxidant parameters in both brain tissue and plasma in rats: catalase, ferric reducing ability of plasma, paraoxonase, protein carbonyl groups, and free thiol groups. Results indicate that both fructose diet and high-fat diet affect the antioxidant capacity of the organism. Furthermore, an addition of cornelian cherry resulted in increased activity of catalase in brain tissue, while in plasma it caused the opposite effect. In turn, with regard to paraoxonase activity in both brain tissue and plasma, it had a stimulating effect. Adding cornelian cherry to the tested diets increased the activity of PON in both tested tissues. Moreover, protective effect of fruits of this plant was observed in the process of oxidation of proteins by decreasing levels of protein carbonyl groups and thiol groups in brain tissue as well as in plasma.

  6. In-service communication channel sensing based on reflectometry for TWDM-PON systems

    Science.gov (United States)

    Iida, Daisuke; Kuwano, Shigeru; Terada, Jun

    2014-05-01

    Many base stations are accommodated in TWDM-PON based mobile backhaul and fronthaul networks for future radio access, and failed connections in an optical network unit (ONU) wavelength channel severely degrade system performance. A cost effective in-service ONU wavelength channel monitor is essential to ensure proper system operation without failed connections. To address this issue we propose a reflectometry-based remote sensing method that provides wavelength channel information with the optical line terminal (OLT)-ONU distance. The method realizes real-time monitoring of ONU wavelength channels without signal quality degradation. Experimental results show it achieves wavelength channel distinction with high distance resolution.

  7. RISET STRATEGI IMPLEMENTASI C-RAN DI TELKOMSEL MELALUI KOLABORASI JARINGAN NG-PON2 DI TELKOM AKSES MENGGUNAKAN PENDEKATAN METODE STRATEGIC SITUATION ANALYSIS

    Directory of Open Access Journals (Sweden)

    Tri Susanto

    2007-07-01

    Full Text Available Cloud Radio Access Network (C-RAN adalah teknologi akses radio yang diyakini mampu menekan biaya CAPEX dan OPEX dari mobile operator dan memberikan performansi yang lebih baik dibandingkan Radio Access Network (RAN tradisional. Salah satu faktor kunci sukses implementasi C-RAN adalah penyediaan jaringan fonthaul yang efektif. Tujuan penelitian ini adalah membuat strategi implementasi C-RAN di Telkomsel melalui kolaborasi jaringan NG-PON2 di Telkom Akses. Pada tulisan ini menggunakan metode analisis kualitatif dengan melakukan strategy situation analysis (SSA yaitu melakukan analisa data eksternal maupun internal dan selanjutnya diformulasikan sebagai dasar pembuatan strategi implementasi. Dari penelitian ini dihasilkan usulan strategi implementasi C-RAN di Telkomsel melalui kolaborasi jaringan NG-PON2 di Telkom Akses.

  8. Evaluation of the Impact of Coherent and Incoherent Crosstalk on the Performance of Wavelength-agnostic WDM-PON Systems

    DEFF Research Database (Denmark)

    Wagner, Christoph; Eiselt, Michael; Grobe, Klaus

    2015-01-01

    Wavelength-agnostic WDM-PON systems recently got a lot of interest as low-cost solution for metro area networking. Here, wavelength-agnostic means that the wavelength from the optical network unit to the optical line terminal is not known by the optical network unit a priori. Furthermore, calibra...

  9. Evaluation of serum oxidative and antioxidative status in patients with erectile dysfunction.

    Science.gov (United States)

    Aldemir, M; Okulu, E; Neşelioğlu, S; Erel, O; Ener, K; Kayıgil, Ö

    2012-05-01

    We evaluated and compared serum oxidative and antioxidative parameters of patients with erectile dysfunction (ED) and control subjects. Twenty married male patients with ED for at least 12 months (Group 1) and 20 volunteer healthy, sexually active, married and age-matched men (Group 2) were included in the study. Group 1 and 2 were compared concerning serum mean total antioxidant capacity (TAC), total oxidant status (TOS), paraoxonase1 (PON1), arylesterase, total thiol and oxidative stress index (OSI). Mean patient age was 47.9 ± 8.1 and 44.4 ± 10.6, respectively, in Group 1 and 2. Serum TAC levels were 1.7 ± 0.5 and 2.3 ± 0.3, respectively, in Group 1 and 2 (P = 0.002). Serum TOS levels were 21.8 ± 20.5 and 11.7 ± 2.2, respectively, in Group 1 and 2 (P = 0.035). Serum PON1 levels were 69.8 ± 13.1 and 164.9 ± 56.5, respectively, in Group 1 and 2 (P total thiol levels were 733.1 ± 253 and 885.5 ± 95.3, respectively, in Group 1 and 2 (P = 0.016). Serum OSI was 0.14 ± 0.17 and 0.05 ± 0.11, respectively, in Group 1 and 2 (P = 0.021). Mean blood platelet count was significantly higher in Group 1 (P = 0.001). A positive correlation between platelets and oxidative state and a negative correlation between platelets and antioxidative state were found. Oxidative stress was detected to be increased, whereas antioxidative parameters were detected to be decreased in patients with ED. © 2011 Blackwell Verlag GmbH.

  10. WDM-PON-compatible system for simultaneous distribution of gigabit baseband and wireless ultrawideband services with flexible bandwidth allocation

    DEFF Research Database (Denmark)

    Pham, Tien Thang; Yu, Xianbin; Gibbon, Timothy Braidwood

    2011-01-01

    In this paper, a novel and simple scheme to realize flexible access for gigabit wireline and impulse radio ultrawideband (IR-UWB) wireless services is proposed. The UWB signals are generated by multi-carrier upconverting and reshaping the baseband signals.The proposed system was experimentally...... demonstrated with the performances of 2.0-Gbps data in both baseband and UWB formats after 46-km single mode fiber transmission and further 0.5-m wireless for UWB data. The flexibility of the system is confirmed by investigating the system performance at different data rates including 1.0 Gbps and 1.6 Gbps....... Optical wavelength independency and data-rate variability of UWB signal generation makes the system attractive for potential wireline and wireless applications in existing WDM-PON systems....

  11. OLT-centralized sampling frequency offset compensation scheme for OFDM-PON.

    Science.gov (United States)

    Chen, Ming; Zhou, Hui; Zheng, Zhiwei; Deng, Rui; Chen, Qinghui; Peng, Miao; Liu, Cuiwei; He, Jing; Chen, Lin; Tang, Xionggui

    2017-08-07

    We propose an optical line terminal (OLT)-centralized sampling frequency offset (SFO) compensation scheme for adaptively-modulated OFDM-PON systems. By using the proposed SFO scheme, the phase rotation and inter-symbol interference (ISI) caused by SFOs between OLT and multiple optical network units (ONUs) can be centrally compensated in the OLT, which reduces the complexity of ONUs. Firstly, the optimal fast Fourier transform (FFT) size is identified in the intensity-modulated and direct-detection (IMDD) OFDM system in the presence of SFO. Then, the proposed SFO compensation scheme including phase rotation modulation (PRM) and length-adaptive OFDM frame has been experimentally demonstrated in the downlink transmission of an adaptively modulated optical OFDM with the optimal FFT size. The experimental results show that up to ± 300 ppm SFO can be successfully compensated without introducing any receiver performance penalties.

  12. Análisis de una red PON UDWDM bajo la influencia de los efectos no lineales

    OpenAIRE

    Yépez Pulles, Pablo Roberto

    2017-01-01

    Today, the way in which information and communication technologies are used have accelerated the development of data networks; this requires more bandwidth and higher transmission speeds every day. The UDWDM-PON (Ultra Dense Wavelength Division Multiplexing – Passive Optical Network) networks are the solution because they are economical in implementation, maintenance, efficient use of bandwidth, and the ability to cover higher information speeds and more users. However, we must be careful wit...

  13. Pomegranate for Your Cardiovascular Health

    Directory of Open Access Journals (Sweden)

    Michael Aviram

    2013-04-01

    Full Text Available 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.

  14. A flexible solution for the next generation EPON with hybrid bidirectional 1Gbps and 10Gbps

    Science.gov (United States)

    Zhang, Weixun; Qiao, Yaojun; Li, Hui; Ji, Yuefeng

    2007-11-01

    Ethernet PON (EPON) has been proved to be a successful technology among all the standardized PON systems [1, 2], in terms of its cost-effective and large bandwidth virtue. And EPON has become a network of a choice for subscriber oriented digital service delivery, taking over the market previously dominated by DSL. However, with the development of advanced video services, the bandwidth capacity of current EPON seems to be not well suited for the future large deployment of triple-play services. Many researches are now taken about the Next Generation EPON; and the recent 10G EPON system standardization effort in the IEEE [3] results a lot of interest in the evolution of current PON systems towards high data rate system capable of providing a future-proof platform for delivery of personalized triple-play services. In this paper, a novel architecture of TDM-based 10GE-PON system is proposed. It combines the GE-PON and 10GE-PON systems, and provides symmetric 1Gbps/10Gbps or asymmetric access simultaneously. According to the results of the simulation on the system throughput and latency performance, the system is verified to be one solution and an important step from 1Gbit/s to 10Gbit/s for the Next Generation EPON.

  15. Performance Analysis of a Hybrid Raman Optical Parametric Amplifier in the O- and E-Bands for CWDM PONs

    Directory of Open Access Journals (Sweden)

    Sasanthi Peiris

    2014-12-01

    Full Text Available We describe a hybrid Raman-optical parametric amplifier (HROPA operating at the O- and E-bands and designed for coarse wavelength division multiplexed (CWDM passive optical networks (PONs. We present the mathematical model and simulation results for the optimization of this HROPA design. Our analysis shows that separating the two amplification processes allows for optimization of each one separately, e.g., proper selection of pump optical powers and wavelengths to achieve maximum gain bandwidth and low gain ripple. Furthermore, we show that the proper design of optical filters incorporated in the HROPA architecture can suppress idlers generated during the OPA process, as well as other crosstalk that leaks through the passive optical components. The design approach enables error free performance for all nine wavelengths within the low half of the CWDM band, assigned to upstream traffic in a CWDM PON architecture, for all possible transmitter wavelength misalignments (±6 nm from the center wavelength of the channel band. We show that the HROPA can achieve error-free performance with a 170-nm gain bandwidth (e.g., 1264 nm–1436 nm, a gain of >20 dB and a gain ripple of <4 dB.

  16. comparative study of glucose homeostasis, lipids and lipoproteins, HDL functionality, and cardiometabolic parameters in modestly severely obese African Americans and White Americans with prediabetes: implications for the metabolic paradoxes.

    Science.gov (United States)

    Healy, Sara J; Osei, Kwame; Gaillard, Trudy

    2015-02-01

    To determine whether modestly severe obesity modifies glucose homeostasis, levels of cardiometabolic markers, and HDL function in African Americans (AAs) and white Americans (WAs) with prediabetes. We studied 145 subjects with prediabetes (N = 61 WAs, N = 84 AAs, mean age 46.5 ± 11.2 years, mean BMI 37.8 ± 6.3 kg/m(2)). We measured fasting levels of lipids, lipoproteins, and an inflammatory marker (C-reactive protein [CRP]); HDL functionality (i.e., levels of paraoxonase 1 [PON1]); and levels of oxidized LDL, adiponectin, and interleukin-6 (IL-6). We measured serum levels of glucose, insulin, and C-peptide during an oral glucose tolerance test. Values for insulin sensitivity index (Si), glucose effectiveness index (Sg), glucose effectiveness at zero insulin (GEZI), and acute insulin response to glucose (AIRg) were derived using a frequently sampled intravenous glucose tolerance test (using MINMOD software). Mean levels of fasting and incremental serum glucose, insulin, and C-peptide tended to be higher in WAs versus AAs. The mean Si was not different in WAs versus AAs (2.6 ± 2.3 vs. 2.9 ± 3.0 × 10(-4) × min(-1) [μU/mL](-1)). Mean values for AIRg and disposition index as well as Sg and GEZI were lower in WAs than AAs. WAs had higher serum triglyceride levels than AAs (116.1 ± 55.5 vs. 82.7 ± 44.2 mg/dL, P = 0.0002). Mean levels of apolipoprotein (apo) A1, HDL cholesterol, PON1, oxidized LDL, CRP, adiponectin, and IL-6 were not significantly different in obese AAs versus WAs with prediabetes. Modestly severe obesity attenuated the ethnic differences in Si, but not in Sg and triglyceride levels in WAs and AAs with prediabetes. Despite the lower Si and PON1 values, AAs preserved paradoxical relationships between the Si and HDL/apoA1/triglyceride ratios. We conclude that modestly severe obesity has differential effects on the pathogenic mechanisms underlying glucose homeostasis and atherogenesis in obese AAs and WAs with prediabetes. © 2015 by the American

  17. Segmental sensory disturbance in brain stem infarctions of the lateral lower pons and lateral medulla

    International Nuclear Information System (INIS)

    Matsumoto, Sadayuki; Yamasaki, Masahiro; Maya, Kiyomi; Imai, Terukuni; Okuda, Bungo.

    1987-01-01

    We reported on seven cases of brainstem infarctions of the lateral lower pons and lateral medulla, the sensory deficit manifested over the trunk or the leg namely segmental sensory disturbances. All patients showed dissociated sensory disturbance of pain and temperature with retained deep sensations except two cases in which touch was also slightly impaired. The sensory distribution was classified into two types. The first ''crossed type'', ipsilatral face and contralateral trunk and leg below the level was involved in 4 cases, and the second ''unilateral type'' contralateral face and trunk above the level in 3 cases. Clinico-anatomical evaluation was executed by MRI. Lesions were detected in the lateral lower pons in two cases and in the lateral medulla in one case. The location of lesions by MRI revealed more lateral lesions showed ''crossed type'' of segmental sensory disturbance and more medial lesions ''unilateral type''. It was shown that the segmental sensory disturbance could be explained by the partial involvement of the lateral spinothalamic tract, which is arranged with the fibers from the sacral segments most lateral. We considered it very important to differentiate the segmental sensory disturbance by brainstem lesion in practical clinical diagnosis. We also emphasize the type of segmental sensory disturbance could be a localizing sign in the lateral brainstem as such, ''crossed type'' indicating the lesion of the lateral portion and ''unilateral type'' the medial portion of the lateral lower brainstem. (author)

  18. Reconfigurable WDM-PON empowered by a low-cost 8-channel directly modulated laser module

    Science.gov (United States)

    Zhang, Yi-ming; Liu, Yu; Zhang, Zhi-ke; Zhao, Ze-ping; Tian, Ye; Zhu, Ning-hua

    2017-11-01

    A 10 Gbit/s 16-km-long reconfigurable wavelength-division-multiplexing passive optical network (WDM-PON) is presented empowered by a low-cost multi-channel directly modulated laser (DML) module. Compared with the case using discrete devices in conventional scheme, the proposed DML module provides a cost-effective solution with reduced complexity. The clear eye diagram and the bit error rate ( BER) of less than 2×10-7 with a sensitivity of -7 dBm are obtained. Due to the special packaging design, the crosstalk between channels under condition of simultaneous operation can be negligible.

  19. Effects of field high temperature on grain yield and quality of a subtropical type japonica rice—Pon-Lai rice

    Directory of Open Access Journals (Sweden)

    Yi-Chien Wu

    2016-01-01

    Full Text Available Typical japonica type rice is sensitive to high temperature. Pon-Lai rice is a special japonica type with adaptation to the subtropical climate in Taiwan. Facing climate change, rising temperatures would damage the yield and quality of rice production. This research was conducted using Pon-Lai rice in the field of a subtropical climate. We conducted 2 experiments, including a year-round experiment and collection of samples from different districts for building different temperature conditions. We analyzed the correlation between rising temperature and rice yield or quality. In our results, the critical period of temperature effect is 0–15 days after heading (H15. The threshold of high temperature damage in yield and appearance quality was 25–27 °C. Grain weight decreased about 2–6%, while the temperature of H15 was raised 1 °C above the thresholds. Perfect grain ratio and chalky grain ratio decreased and increased, respectively, while the temperature of H15 was raised above the thresholds. However, the high temperature in H15 affected the physicochemical characteristics. In addition, we found positive correlation between grain length to width ratio and perfect grain ratio. Grain length to width ratio could be an index of temperature effects for grain quality. In our study, when the temperature was below 30 °C, a rising temperature of H15 could damage rice yield and appearance quality, and change grain shape. Our results could provide reference for dealing with the warming future in other temperate rice-cultivated countries.

  20. Selected serum oxidative stress biomarkers in dogs with non-food-induced and food-induced atopic dermatitis.

    Science.gov (United States)

    Almela, Ramón M; Rubio, Camila P; Cerón, José J; Ansón, Agustina; Tichy, Alexander; Mayer, Ursula

    2018-06-01

    Oxidative stress (OS) has been shown to be involved in the pathogenesis of human and canine atopic dermatitis (AD) through several distinct mechanisms. Selected serum biomarkers of OS (sbOS) have been validated in normal dogs and studied in several canine diseases. To the best of the authors' knowledge, the sbOS evaluated in this study have not previously been described in canine AD. The aims of the study were to evaluate a panel of sbOS in dogs with food-induced (FIAD) and non-food-induced (NFIAD) AD: cupric reducing antioxidant capacity (CUPRAC), ferrous oxidation-xylenol orange (FOX), ferric reducing ability of the plasma (FRAP), paraoxonase-1 (PON1), trolox equivalent antioxidant capacity (TEAC) and serum total thiol (THIOL). The aim was to compare these metabolites with those in healthy control dogs, and to correlate sbOS with validated pruritus and CADESI-04 severity scales in dogs with AD. Forty six healthy, nine NFIAD and three FIAD client-owned dogs were included. The study was designed as a cohort study. There were significant differences in atopic dogs when compared to healthy dogs for all of the sbOS analysed. These findings suggest that OS could play a role in the pathogenesis of canine NFIAD and FIAD. In addition, the evaluation of sbOS could be useful for precision medicine to help to detect atopic dogs that might benefit from antioxidant-targeted therapies. © 2018 ESVD and ACVD.

  1. Computational enzymology for degradation of chemical warfare agents: promising technologies for remediation processes

    Directory of Open Access Journals (Sweden)

    2017-03-01

    Full Text Available Chemical weapons are a major worldwide problem, since they are inexpensive, easy to produce on a large scale and difficult to detect and control. Among the chemical warfare agents, we can highlight the organophosphorus compounds (OP, which contain the phosphorus element and that have a large number of applications. They affect the central nervous system and can lead to death, so there are a lot of works in order to design new effective antidotes for the intoxication caused by them. The standard treatment includes the use of an anticholinergic combined to a central nervous system depressor and an oxime. Oximes are compounds that reactivate Acetylcholinesterase (AChE, a regulatory enzyme responsible for the transmission of nerve impulses, which is one of the molecular targets most vulnerable to neurotoxic agents. Increasingly, enzymatic treatment becomes a promising alternative; therefore, other enzymes have been studied for the OP degradation function, such as phosphotriesterase (PTE from bacteria, human serum paraoxonase 1 (HssPON1 and diisopropyl fluorophosphatase (DFPase that showed significant performances in OP detoxification. The understanding of mechanisms by which enzymes act is of extreme importance for the projection of antidotes for warfare agents, and computational chemistry comes to aid and reduce the time and costs of the process. Molecular Docking, Molecular Dynamics and QM/MM (quantum-mechanics/molecular-mechanics are techniques used to investigate the molecular interactions between ligands and proteins.

  2. Association of Multiple Genetic Variants with the Extension and Severity of Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Simone Cristina Pinto Matheus Fischer

    2018-02-01

    Full Text Available Abstract Background: Metabolic syndrome (MS is a condition that, when associated with ischemic heart disease and cardiovascular events, can be influenced by genetic variants and determine more severe coronary atherosclerosis. Objectives: To examine the contribution of genetic polymorphisms to the extension and severity of coronary disease in subjects with MS and recent acute coronary syndrome (ACS. Methods: Patients (n = 116, 68% males aged 56 (9 years, with criteria for MS, were prospectively enrolled to the study during the hospitalization period after an ACS. Clinical and laboratory parameters, high-sensitivity C-reactive protein, thiobarbituric acid reactive substances, adiponectin, endothelial function, and the Gensini score were assessed. Polymorphisms of paraoxonase-1 (PON-1, methylenotetrahydrofolate reductase (MTHFR, endothelial nitric oxide synthase (ENOS, angiotensin-converting enzyme (ACE, angiotensin II type 1 receptor (AT1R, apolipoprotein C3 (APOC3, lipoprotein lipase (LPL were analysed by polymerase chain reaction (PCR technique, followed by the identification of restriction fragment length polymorphisms (RFLP, and a genetic score was calculated. Parametric and non-parametric tests were used, as appropriate. Significance was set at p < 0.05. Results: Polymorphisms of PON-1, MTHFR and ENOS were not in the Hardy-Weinberg equilibrium. The DD genotype of LPL was associated with higher severity and greater extension of coronary lesions. Genetic score tended to be higher in patients with Gensini score < P50 (13.7 ± 1.5 vs. 13.0 ± 1.6, p = 0.066, with an inverse correlation between genetic and Gensini scores (R = -0.194, p = 0.078. Conclusions: The LPL polymorphism contributed to the severity of coronary disease in patients with MS and recent ACS. Combined polymorphisms were associated with the extension of coronary disease, and the lower the genetic score the more severe the disease.

  3. A novel PON based UMTS broadband wireless access network architecture with an algorithm to guarantee end to end QoS

    Science.gov (United States)

    Sana, Ajaz; Hussain, Shahab; Ali, Mohammed A.; Ahmed, Samir

    2007-09-01

    In this paper we proposes a novel Passive Optical Network (PON) based broadband wireless access network architecture to provide multimedia services (video telephony, video streaming, mobile TV, mobile emails etc) to mobile users. In the conventional wireless access networks, the base stations (Node B) and Radio Network Controllers (RNC) are connected by point to point T1/E1 lines (Iub interface). The T1/E1 lines are expensive and add up to operating costs. Also the resources (transceivers and T1/E1) are designed for peak hours traffic, so most of the time the dedicated resources are idle and wasted. Further more the T1/E1 lines are not capable of supporting bandwidth (BW) required by next generation wireless multimedia services proposed by High Speed Packet Access (HSPA, Rel.5) for Universal Mobile Telecommunications System (UMTS) and Evolution Data only (EV-DO) for Code Division Multiple Access 2000 (CDMA2000). The proposed PON based back haul can provide Giga bit data rates and Iub interface can be dynamically shared by Node Bs. The BW is dynamically allocated and the unused BW from lightly loaded Node Bs is assigned to heavily loaded Node Bs. We also propose a novel algorithm to provide end to end Quality of Service (QoS) (between RNC and user equipment).The algorithm provides QoS bounds in the wired domain as well as in wireless domain with compensation for wireless link errors. Because of the air interface there can be certain times when the user equipment (UE) is unable to communicate with Node B (usually referred to as link error). Since the link errors are bursty and location dependent. For a proposed approach, the scheduler at the Node B maps priorities and weights for QoS into wireless MAC. The compensations for errored links is provided by the swapping of services between the active users and the user data is divided into flows, with flows allowed to lag or lead. The algorithm guarantees (1)delay and throughput for error-free flows,(2)short term fairness

  4. A Pontine Region is a Neural Correlate of the Human Affective Processing Network

    Directory of Open Access Journals (Sweden)

    Tatia M.C. Lee

    2015-11-01

    Full Text Available The in vivo neural activity of the pons during the perception of affective stimuli has not been studied despite the strong implications of its role in affective processing. To examine the activity of the pons during the viewing of affective stimuli, and to verify its functional and structural connectivity with other affective neural correlates, a multimodal magnetic resonance imaging methodology was employed in this study. We observed the in vivo activity of the pons when viewing affective stimuli. Furthermore, small-world connectivity indicated that the functional connectivity (FC between the pons and the cortico-limbic affective regions was meaningful, with the coefficient λ being positively associated with self-reported emotional reactivity. The FC between the pons and the cortico-limbic-striatal areas was related to self-reported negative affect. Corroborating this finding was the observation that the tract passing through the pons and the left hippocampus was negatively related to self-reported positive affect and positively correlated with emotional reactivity. Our findings support the framework that the pons works conjunctively with the distributed cortico-limbic-striatal systems in shaping individuals' affective states and reactivity. Our work paves the path for future research on the contribution of the pons to the precipitation and maintenance of affective disorders.

  5. Evaluation of oxidative stress status and antioxidant capacity in patients with painful bladder syndrome/interstitial cystitis: preliminary results of a randomised study.

    Science.gov (United States)

    Ener, Kemal; Keske, Murat; Aldemir, Mustafa; Özcan, Muhammet Fuat; Okulu, Emrah; Özayar, Asım; Ergin, Merve; Doluoğlu, Ömer Gökhan; Çakmak, Serdar; Erel, Özcan

    2015-08-01

    This study aimed to investigate oxidative stress in etiopathogenesis by analyzing serum total antioxidant capacity (TAC), total oxidant status (TOS), binding capacity of exogenous cobalt to human albumin (IMA), serum advanced oxidation protein products (AOPP), paraoxonase (PON), arylesterase, IgE, and C-reactive protein (CRP) in bladder pain syndrome/interstitial cystitis (BPS/IC). The study included 16 female patients diagnosed with BPS/IC and 25 healthy female subjects forming the control group. A bladder biopsy was performed on all patients in the BPS/IC group by carrying out cystoscopy with hydrodistention under general anesthesia. The results of serum TAC, TOS, IMA, AOPP, PON, arylesterase, IgE, and CRP of the subjects in both groups were compared. The mean age of the 16 female patients in the BPS/IC group was 43.6 ± 14.5 years, and the mean age of the 25 healthy subjects in the control group was 42.0 ± 10.3 years. According to the criteria of International Society for the Study of Interstitial Cystitis (ESSIC), eight patients were classified as Type 2A, three patients as Type 2B, four patients as Type 2C, and one patient as Type 3C. In the BPS/IC group, while TAC was found significantly lower than in the control group, IMA, IgE, and CRP were found significantly higher (P < 0.05). When binary logistic regression analysis was performed, the created model was determined to have 81.3 % sensitivity and 80 % specifity. In the etiology of BPS/IC, mechanism of oxidative damage comes into prominence. In the diagnosis of BPS/IC, IgE, CRP, and TAC are not specific markers when used separately; however, a higher specifity and sensitivity could be reached when used jointly in the suspected patients.

  6. Association between diet and polymorphisms in individuals with statin-controlled dyslipidaemia grouped according to oxidative stress biomarkers

    Directory of Open Access Journals (Sweden)

    Patrícia Borges Botelho

    2012-03-01

    Full Text Available The objective of this study was to investigate whether differences in diet and in single-nucleotide polymorphisms (SNPs found in paraoxonase-1 (PON-1, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR, cholesterol ester transfer protein (CETP and apolipoprotein E (APOE genes, are associated with oxidative stress biomarkers and consequently with susceptibility of low-density cholesterol (LDL to oxidation. A multivariate approach was applied to a group of 55 patients according to three biomarkers: plasma antioxidant activity, malondialdehyde and oxidized LDL (oxLDL concentrations. Individuals classified in Cluster III showed the worst prognoses in terms of antioxidant activity and oxidative status. Individuals classified in Cluster I presented the lowest oxidative status, while individuals grouped in Cluster II presented the highest levels of antioxidant activity. No difference in nutrient intake was observed among the clusters. Significantly higher γ- and δ-tocopherol concentrations were observed in those individuals with the highest levels of antioxidant activity. No single linear regression was statistically significant, suggesting that mutant alleles of the SNPs selected did not contribute to the differences observed in oxidative stress response. Although not statistically significant, the p value of the APO E coefficient for oxLDL response was 0.096, indicating that patients who carry the TT allele of the APO E gene tend to present lower plasma oxLDL concentrations. Therefore, the differences in oxidative stress levels observed in this study could not be attributed to diet or to the variant alleles of PON-1, CETP, HMGCR or APO E. This data supports the influence of γ-tocopherol and δ-tocopherol on antioxidant activity, and highlights the need for further studies investigating APO E alleles and LDL oxidation.O objetivo deste estudo foi investigar se diferenças na dieta e em polimorfismos de nucleotídeos únicos (SNPs encontrados no

  7. Effects of vitamin A, C and E, or omega-3 fatty acid supplementation on the level of paraoxonase and arylesterase activity in streptozotocin-induced diabetic rats: an investigation of activities in plasma, and heart and liver homogenates.

    Science.gov (United States)

    Zarei, Mahnaz; Fakher, Shima; Tabei, Seyed Mohammad Bagher; Javanbakht, Mohammad Hassan; Derakhshanian, Hoda; Farahbakhsh-Farsi, Payam; Sadeghi, Mohammad Reza; Mostafavi, Ebrahim; Djalali, Mahmoud

    2016-03-01

    This study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fatty acid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus. A total of 64 male Sprague Dawley® rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fatty acid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured. Arylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p Vitamin A, C and E supplementation, and omega-3 fatty acid supplementation significantly increased liver arylesterase activity (p Vitamin A, C and E, or omega-3 fatty acid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications. Copyright: © Singapore Medical Association.

  8. Synergistic convergence and split pons in horizontal gaze palsy and progressive scoliosis in two sisters

    Directory of Open Access Journals (Sweden)

    Jain Nitin

    2011-01-01

    Full Text Available Synergistic convergence is an ocular motor anomaly where on attempted abduction or on attempted horizontal gaze, both the eyes converge. It has been related to peripheral causes such as congenital fibrosis of extraocular muscles (CFEOM, congenital cranial dysinnervation syndrome, ocular misinnervation or rarely central causes like horizontal gaze palsy with progressive scoliosis, brain stem dysplasia. We hereby report the occurrence of synergistic convergence in two sisters. Both of them also had kyphoscoliosis. Magnetic resonance imaging (MRI brain and spine in both the patients showed signs of brain stem dysplasia (split pons sign differing in degree (younger sister had more marked changes.

  9. Grape Polyphenols Increase the Activity of HDL Enzymes in Old and Obese Rats

    Directory of Open Access Journals (Sweden)

    Andriy L. Zagayko

    2013-01-01

    Full Text Available HDL particles are protein-rich particles that act as a vehicle for reverse cholesterol transport from tissues to the liver. The purpose of this study was to investigate age-dependent changes in the functional activity of HDL and the effect of high-energy diet on this index, as well as to correct it under the influence of grape polyphenols from “Enoant” obtained from Vitis vinifera grapes. We observed the age-dependent composition changes in HDL particle. It was shown that total lipids and triacylglycerol (TG levels were higher in 24-month-old animals. In obese rats, HDL total lipids and TG levels were higher in 24-month-old than in the 3-month-old and 12-month-old groups but did not differ from 24-month-old group. The plasma HDL paraoxonase (PON and lecithin:cholesterol acyltransferase (LCAT activity levels were decreased in old-aged rats, and cholesteryl ester transfer protein (CETP activity was higher in old rats. Keeping 12-month-old animals on high-fructose diet completely leveled the age differences in the data that have been measured between 12-month-old and 24-month-old rats. After “Enoant” administration, an increase of HDL PON and LCAT activity levels and a reduction of CETP activity were found in 24-month-old and obese rats.

  10. The effect of ginger (Zingiber officinale) on glycemic markers in patients with type 2 diabetes.

    Science.gov (United States)

    Shidfar, Farzad; Rajab, Asadollah; Rahideh, Tayebeh; Khandouzi, Nafiseh; Hosseini, Sharieh; Shidfar, Shahrzad

    2015-06-01

    Ginger (Zingiber officinale) is one of the functional foods which contains biological compounds including gingerol, shogaol, paradol and zingerone. Ginger has been proposed to have anti-cancer, anti-thrombotic, anti-inflammatory, anti-arthritic, hypolipidemic and analgesic properties. Here, we report the effect of ginger supplementation on glycemic indices in Iranian patients with type 2 diabetes. A double-blind, placebo-controlled, randomized clinical trial was conducted on 20-60 -year-old patients with type 2 diabetes who did not receive insulin. Participants in the intervention and control groups were received 3 g of powdered ginger or placebo (lactose) (in capsules) daily for 3 months. Glycemic indices, total antioxidant capacity (TAC), malondialdehyde (MDA), C-reactive protein (CRP), serum paraoxonase, dietary intake and physical activity were measured at the beginning and end of the study, and after 12 h fasting. Comparison of the indices after 3 months showed that the differences between the ginger and placebo groups were statistically significant as follows: serum glucose (-19.41 ± 18.83 vs. 1.63 ± 4.28 mg/dL, p ginger improved glycemic indices, TAC and PON-1 activity in patients with type 2 diabetes.

  11. Possible role of selective serotonin reuptake inhibitor sertraline on oxidative stress responses.

    Science.gov (United States)

    Battal, D; Yalin, S; Eker, E D; Aktas, A; Sahin, N O; Cebo, M; Berköz, M

    2014-01-01

    The naphthylamine derivative sertraline is a potent and selective inhibitor of serotonin reuptake into presynaptic terminals and the most widely used that has been shown to have both antidepressant and antianxiety effects. In the present study the possible role of sertraline (acute and chronically doses) was evaluated on lipid peroxidation levels and antioxidant enzyme activities in plasma and brain tissues of (10, 40, 80 mg/kg) sertraline treated Wistar albino rats (n=48). Lipid peroxidation levels (MDA) of plasma and brain tissue increased in all acute and chronic sertraline treated rats (p Catalase (CAT) levels of plasma and brain tissue and paraoxonase (PON) levels of plasma decreased (p < 0.05) as compared with vehicle group. Based on the data, it can be concluded that high dose sertraline administration enhances oxidative stress. Therefore, dose adjustment in depression patients seems significant as it may help prevention of further prognosis of the diseases.

  12. 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.

  13. Effect of taurine supplementation on hyperhomocysteinemia and markers of oxidative stress in high fructose diet induced insulin resistance

    Directory of Open Access Journals (Sweden)

    El Mesallamy Hala O

    2010-06-01

    Full Text Available Abstract Background High intake of dietary fructose is accused of being responsible for the development of the insulin resistance (IR syndrome. Concern has arisen because of the realization that fructose, at elevated concentrations, can promote metabolic changes that are potentially deleterious. Among these changes is IR which manifests as a decreased biological response to normal levels of plasma insulin. Methods Oral glucose tolerance tests (OGTT were carried out, homeostasis model assessment of insulin resistance (HOMA was calculated, homocysteine (Hcy, lipid concentrations and markers of oxidative stress were measured in male Wistar rats weighing 170-190 g. The rats were divided into four groups, kept on either control diet or high fructose diet (HFD, and simultaneously supplemented with 300 mg/kg/day taurine via intra-peritoneal (i.p. route for 35 days. Results Fructose-fed rats showed significantly impaired glucose tolerance, impaired insulin sensitivity, hypertriglyceridemia, hypercholesterolemia, hyperhomocysteinemia (HHcy, lower total antioxidant capacity (TAC, lower paraoxonase (PON activity, and higher nitric oxide metabolites (NOx concentration, when compared to rats fed on control diet. Supplementing the fructose-fed rats with taurine has ameliorated the rise in HOMA by 56%, triglycerides (TGs by 22.5%, total cholesterol (T-Chol by 11%, and low density lipoprotein cholesterol (LDL-C by 21.4%. Taurine also abolished any significant difference of TAC, PON activity and NOx concentration among treated and control groups. TAC positively correlated with PON in both rats fed on the HFD and those received taurine in addition to the HFD. Fructose-fed rats showed 34.7% increase in Hcy level. Taurine administration failed to prevent the observed HHcy in the current dosage and duration. Conclusion Our results indicate that HFD could induce IR which could further result in metabolic syndrome (MS, and that taurine has a protective role against

  14. Enhanced noise tolerance for 10 Gb/s Bi-directional cross-wavelength reuse colorless WDM-PON by using spectrally shaped OFDM signals

    Science.gov (United States)

    Choudhury, Pallab K.

    2018-05-01

    Spectrally shaped orthogonal frequency division multiplexing (OFDM) signal for symmetric 10 Gb/s cross-wavelength reuse reflective semiconductor optical amplifier (RSOA) based colorless wavelength division multiplexed passive optical network (WDM-PON) is proposed and further analyzed to support broadband services of next generation high speed optical access networks. The generated OFDM signal has subcarriers in separate frequency ranges for downstream and upstream, such that the re-modulation noise can be effectively minimized in upstream data receiver. Moreover, the cross wavelength reuse approach improves the tolerance against Rayleigh backscattering noise due to the propagation of different wavelengths in the same feeder fiber. The proposed WDM-PON is successfully demonstrated for 25 km fiber with 16-QAM (quadrature amplitude modulation) OFDM signal having bandwidth of 2.5 GHz for 10 Gb/s operation and subcarrier frequencies in 3-5.5 GHz and DC-2.5 GHz for downstream (DS) and upstream (US) transmission respectively. The result shows that the proposed scheme maintains a good bit error rate (BER) performance below the forward error correction (FEC) limit of 3.8 × 10-3 at acceptable receiver sensitivity and provides a high resilience against re-modulation and Rayleigh backscattering noises as well as chromatic dispersion.

  15. High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted MR Images: Comparison between Gadobutrol and Linear Gadolinium-Based Contrast Agents.

    Science.gov (United States)

    Moser, F G; Watterson, C T; Weiss, S; Austin, M; Mirocha, J; Prasad, R; Wang, J

    2018-02-01

    In view of the recent observations that gadolinium deposits in brain tissue after intravenous injection, our aim of this study was to compare signal changes in the globus pallidus and dentate nucleus on unenhanced T1-weighted MR images in patients receiving serial doses of gadobutrol, a macrocyclic gadolinium-based contrast agent, with those seen in patients receiving linear gadolinium-based contrast agents. This was a retrospective analysis of on-site patients with brain tumors. Fifty-nine patients received only gadobutrol, and 60 patients received only linear gadolinium-based contrast agents. Linear gadolinium-based contrast agents included gadoversetamide, gadobenate dimeglumine, and gadodiamide. T1 signal intensity in the globus pallidus, dentate nucleus, and pons was measured on the precontrast portions of patients' first and seventh brain MRIs. Ratios of signal intensity comparing the globus pallidus with the pons (globus pallidus/pons) and dentate nucleus with the pons (dentate nucleus/pons) were calculated. Changes in the above signal intensity ratios were compared within the gadobutrol and linear agent groups, as well as between groups. The dentate nucleus/pons signal ratio increased in the linear gadolinium-based contrast agent group ( t = 4.215, P linear gadolinium-based contrast agent group ( t = 2.931, P linear gadolinium-based contrast agents. © 2018 by American Journal of Neuroradiology.

  16. Book 1

    African Journals Online (AJOL)

    lipoproteins (HDL)11. Although the nat- ural substrate(s) of this enzyme are un- known, it is capable of the hydrolysis of a variety of xenobiotics, including or- ganophosphates and aryl esters that are common components of insecticides and nerve agents12. Paraoxonase has been shown to metabolize lipid-soluble radicals ...

  17. On-the-field performance of quintuple-play long-reach OFDM-based WDM-PON optical access networks.

    Science.gov (United States)

    Llorente, Roberto; Morant, Maria; Pellicer, Eloy; Herman, Milan; Nagy, Zsolt; Alves, Tiago; Cartaxo, Adolfo; Herrera, Javier; Correcher, Jose; Quinlan, Terence; Walker, Stuart; Rodrigues, Cláudio; Cluzeaud, Pierre; Schmidt, Axel; Piesiewicz, Radoslaw; Sambaraju, Rakesh

    2014-03-24

    In this paper the on-the-field performance of a WDM-PON optical access providing quintuple-play services using orthogonal frequency division multiplexing (OFDM) modulation is evaluated in a real fiber-to-the-home (FTTH) network deployed by Towercom operator in Bratislava (Slovakia). A bundle of quintuple-play services comprising full-standard OFDM-based signals (LTE, WiMAX, UWB and DVB-T) and an ad-hoc OFDM-GbE signal is transmitted in coexistence per single user. Both downstream and upstream transmission performances are evaluated in different on-the-field long-reach optical link distance configurations. Four wavelength multi-user transmission of quintuple-play OFDM services is demonstrated exceeding 60.8 km reach in standard single mode fiber.

  18. A new method of equalizing the optical power by a liquid crystal-based tunable encoder/decoder in SAC-OCDMA PON

    Science.gov (United States)

    Chen, He; Qiao, Yang; Zhao, Yanbin; Liu, Yang; Liu, Meilin; Liu, Lijun; Zhou, Bilei

    2015-11-01

    A new method of equalizing the optical power is proposed to enhance the performance in the SAC OCDMA PON. The method is to use a tunable liquid crystal-based tunable encoder for further development by voltage controlling individually, so it is achieved in one device for encoding and power equalization, the experimental results show that the system BER and eye diagram are greatly improved. Since the method does not use additional devices in the condition, the system are lower complexity and cost-effective.

  19. Two Cases of Acute Disseminated Encephalomyelitis Following Vaccination Against Human Papilloma Virus

    Science.gov (United States)

    Sekiguchi, Kenji; Yasui, Naoko; Kowa, Hisatomo; Kanda, Fumio; Toda, Tatsushi

    2016-01-01

    We herein present two cases of acute disseminated encephalomyelitis (ADEM) following vaccination against human papilloma virus (HPV). Case 1 experienced diplopia and developed an unstable gait 14 days after a second vaccination of Cervarix. Brain magnetic resonance imaging (MRI) showed an isolated small, demyelinating lesion in the pontine tegmentum. Case 2 experienced a fever and limb dysesthesia 16 days after a second vaccination of Gardasil. Brain MRI revealed hyperintense lesion in the pons with slight edema on a T2-weighted image. Both cases resolved completely. It is important to accumulate further data on confirmed cases of ADEM temporally associated with HPV vaccination. PMID:27803416

  20. Localized single voxel 1H MR spectroscopy toward routine clinical use

    International Nuclear Information System (INIS)

    Lee, Jung Hee; Choi, Choong Gon; Kim, Sang Tae; Kim, Jin Suh; Mun, Chi Woong; Suh, Dae Chul; Lim, Tae Hwan; Auh, Young Ho

    1996-01-01

    To evaluate the automated 1 H magnetic resonance spectroscopy ( 1 H-MRS) method for a routine clinical use, various regions of the normal human brain were examined for regional variations, the reproducibility, and the quality control of the spectral data. Localized 1 H-MRS was performed in a GE 1.5T SIGNA MRI/MRS system using the automated method (PROton Brain Exam:PROBE). Six regions of the human brain from normal volunteers (N=25, age=23-65) were examined: Occipital gray matter, parietal white matter, frontal white matter, pons, cerebellum, and basal ganglia region. STEAM was used as the localization method with the following parameters : TE=30 msec, TR=3.0 sec, AVG=48 AVG, NEX=2, Spectral Width (SW)=2500 Hz, Size (SI)=2048 points (2K), and the size of voxel=7-9 ml. The reproducibility and the quality control of the spectral data were evaluated. For the 6 regions, the regional variation by the spectral patterns and the metabolites ratios relative to creatine was well demonstrated. Rates of the auto prescan success and the percentages of obtaining the acceptable quality spectral were high in the parietal white matter, occipital gray matter, and basal ganglia regions, and low in the frontal white matter and pons regions. PROBE is a highly practical as well as reliable method to produce reproducible quality spectra that represent the regional metabolic exam or as an additional series to a routine brain MRI exam, which takes less than 10 minutes for acquisition of one spectrum. In order to obtain good quality spectra, a good quality control scheme of the MR instrument is mandatory

  1. Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.

    Science.gov (United States)

    Eylers, V V; Maudsley, A A; Bronzlik, P; Dellani, P R; Lanfermann, H; Ding, X-Q

    2016-03-01

    Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain (1)H-MRS was used in combination with quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure. Sixty healthy volunteers, 21-70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2' were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data. Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2' decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2' in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2' in the putamen. The effects of normal aging on brain metabolites and microstructure are region-dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients. © 2016 by American Journal of Neuroradiology.

  2. Self-homodyne optical OFDM for broadband WDM-PONs with crosstalk-free remodulation and enhanced tolerance to Rayleigh noise

    Science.gov (United States)

    Lyu, WeiChao; Wang, Andong; Xie, Dequan; Zhu, Long; Guan, Xun; Wang, Jian; Xu, Jing

    2018-05-01

    We propose a novel architecture for wavelength-division-multiplexed passive optical network (WDM-PON) that can simultaneously circumvent both remodulation crosstalk and Rayleigh noise, based on self-homodyne detection and optical orthogonal frequency-division multiplexing (OFDM) remodulation. The proposed self-homodyne detection at optical network unit (ONU) requires neither frequency offset compensation nor phase noise compensation, and thus can significantly reduce system complexity and power consumption. Bidirectional transmission of 12.5 Gb/s down- and up-stream signals, via single 25 km single-mode fiber without dispersion compensation, is demonstrated in a proof-of-concept experiment.

  3. Design and implementation of digital television over ethernet PON transmission system

    Science.gov (United States)

    Lu, Xi; Liu, Deming; Mao, Minjing; Wang, Jinjuan

    2005-11-01

    There are two primary methods of transmitting signal of digital television to the home in China. The first one is HFC mode, which is widely used. The other is IPTV mode, which is emerging. In this paper, the scheme of digital television over Ethernet PON is proposed. There are several differences from this system to IPTV and Video over LAN: the real-time transmission of equal-bandwidth based on statistical multiplexing, channel switching based on multicast and IP CA system, etc.. And these are also the key techniques used in this system. The architecture of DTV over EPON system, the function of every component, the framing process and the multiplexing of Ethernet frame are described. The implementation procedure of the system is shown. The mechanism of channel switching using multicast technique is designed and realized. We also present the method of using static VLAN and IGMP snooping mechanism to implement statistical multiplexing on Ethernet layer, and put forward the concept of IP Conditional Access System and define it. An experimental system of DTV over EPON is set up and the experimental result is significant.

  4. Design and performance investigation of LDPC-coded upstream transmission systems in IM/DD OFDM-PONs

    Science.gov (United States)

    Gong, Xiaoxue; Guo, Lei; Wu, Jingjing; Ning, Zhaolong

    2016-12-01

    In Intensity-Modulation Direct-Detection (IM/DD) Orthogonal Frequency Division Multiplexing Passive Optical Networks (OFDM-PONs), aside from Subcarrier-to-Subcarrier Intermixing Interferences (SSII) induced by square-law detection, the same laser frequency for data sending from Optical Network Units (ONUs) results in ONU-to-ONU Beating Interferences (OOBI) at the receiver. To mitigate those interferences, we design a Low-Density Parity Check (LDPC)-coded and spectrum-efficient upstream transmission system. A theoretical channel model is also derived, in order to analyze the detrimental factors influencing system performances. Simulation results demonstrate that the receiver sensitivity is improved 3.4 dB and 2.5 dB under QPSK and 8QAM, respectively, after 100 km Standard Single-Mode Fiber (SSMF) transmission. Furthermore, the spectrum efficiency can be improved by about 50%.

  5. Novel toggle-rate based energy-efficient scheme for heavy load real-time IM-DD OFDM-PON with ONU LLID identification in time-domain using amplitude decision.

    Science.gov (United States)

    Qin, Youxiang; Zhang, Junjie

    2017-07-10

    A novel low complexity and energy-efficient scheme by controlling the toggle-rate of ONU with time-domain amplitude identification is proposed for a heavy load downlink in an intensity-modulation and direct-detection orthogonal frequency division multiplexing passive optical network (IM-DD OFDM-PON). In a conventional OFDM-PON downlink, all ONUs have to perform demodulation for all the OFDM frames in a broadcast way no matter whether the frames are targeted to or not, which causes a huge energy waste. However, in our scheme, the optical network unit (ONU) logical link identifications (LLIDs) are inserted into each downlink OFDM frame in time-domain at the optical line terminal (OLT) side. At the ONU side, the LLID is obtained with a low complexity and high precision amplitude identification method. The ONU sets the toggle-rate of demodulation module to zero when the frames are not targeted to, which avoids unnecessary digital signal processing (DSP) energy consumption. Compared with the sleep-mode methods consisting of clock recovery and synchronization, toggle-rate shows its advantage in fast changing, which is more suitable for the heavy load scenarios. Moreover, for the first time to our knowledge, the characteristics of the proposed scheme are investigated in a real-time IM-DD OFDM system, which performs well at the received optical power as low as -21dBm. The experimental results show that 25.1% energy consumption can be saved in the receiver compared to the conventional configurations.

  6. 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

  7. 40-Gb/s PAM4 with low-complexity equalizers for next-generation PON systems

    Science.gov (United States)

    Tang, Xizi; Zhou, Ji; Guo, Mengqi; Qi, Jia; Hu, Fan; Qiao, Yaojun; Lu, Yueming

    2018-01-01

    In this paper, we demonstrate 40-Gb/s four-level pulse amplitude modulation (PAM4) transmission with 10 GHz devices and low-complexity equalizers for next-generation passive optical network (PON) systems. Simple feed-forward equalizer (FFE) and decision feedback equalizer (DFE) enable 20 km fiber transmission while high-complexity Volterra algorithm in combination with FFE and DFE can extend the transmission distance to 40 km. A simplified Volterra algorithm is proposed for reducing computational complexity. Simulation results show that the simplified Volterra algorithm reduces up to ∼75% computational complexity at a relatively low cost of only 0.4 dB power budget. At a forward error correction (FEC) threshold of 10-3 , we achieve 31.2 dB and 30.8 dB power budget over 40 km fiber transmission using traditional FFE-DFE-Volterra and our simplified FFE-DFE-Volterra, respectively.

  8. Neonatology oxidative status in preterm infants with premature preterm rupture of membranes and fetal inflammatuar response syndrome.

    Science.gov (United States)

    Özalkaya, Elif; Karatekin, Güner; Topçuoğlu, Sevilay; Karatepe, Hande Özgün; Hafızoğlu, Taner; Baran, Pervin; Ovalı, Fahri

    2017-10-01

    The aim of this study, to determine an index of oxidative stress index in preterm infants less than 34 weeks gestational age with premature preterm rupture of membrane (PPROM) and fetal inflammatory response syndrome (FIRS). This study was designed as a prospective study. Fifty-one premature infants less than 35 weeks of gestational age were included in the study. The umbilical cord blood concentrations of IL-6, TAC (total antioxidant capacity) and PON-1 (paraoxonase-1) levels and TOS (total oxidative stress) were studied. The oxidative stress index (OSI = TAC/TOS) was calculated in all of prematüre infants. PPROM was defined as rupture of membranes at least 24 hours before the onset of labor. FIRS was defined by an umbilical cord IL-6 level greater than 11 pg/mL. Premature infants included in the study were divided into 4 groups. Group 1 included preterm infants without FIRS and with PPROM (n = 16), while Group 2 included preterm infants without PPROM and with FIRS (n = 9), Group 3 consisted of premature infants with PPROM and FIRS (n = 21) and Group 4 included premature infants without PPROM or FIRS (n = 5). Umbilical cord TOS level was found to be higher in the preterm infants without FIRS and with PPROM (36.1 μmol H 2 O 2 Equiv./L) compared to the preterm infants without PPROM or FIRS (11.9 μmol H 2 O 2 Equiv./L) (p = 0.03). Umbilical cord PON-1 level was found to be lower in the preterms without FIRS and with PPROM (32 U/L), preterms without PPROM and with FIRS (30. 3 U/L) and the preterm infants with both PPROM and FIRS (48.6 U/L) compared to the preterm infants having no PPROM or FIRS (85.6 U/L) (p = 0.001). High pro-oxidant capacity was found in PPROM and low antioxidant capacity in PPROM and FIRS. Copyright © 2017. Published by Elsevier B.V.

  9. Cytotoxic Effects of Ionizing Radiation and Chlorpyrifos on White Rats

    International Nuclear Information System (INIS)

    El-Bahkery, A.M.L.H.

    2014-01-01

    The hazard of accidental exposure to ionizing radiation (IR) and/or neurotoxic insecticides like the organophosphorus insecticide chlorpyrifos (CPF) represent series health problem for human. In the present work, the cytotoxic effects of ionizing radiation and chlorpyrifos on rats were studied where animals were under glutathione (GSH) depletion. Animals were pre-treated with single dose of Buthionine Sulfoximine (BSO) (200 mg/kg body weight, by oral intubation), then treated with high dose of CPF (30 mg/kg body weight) and or exposure to IR (single dose of 6 Gy whole body gamma ray) one hour after BSO treatment. Another groups of animals pertreated with N-acetyl cystiene (NAC) one hour before treated with CPF and/or IR. After 24 hours blood sample, liver and brain were taken and used for estimate the GSH level and the activities of glutathione-stransferase (GST), glutathione reductase (GR), acetyl cholinesterase (AChE), carboxyl esterase (CE), paraoxonase (PON) and arylesterase (AE). Also, native PAGE electrophoresis was undertaken for separating the CE and PON isozymes in plasma, liver and brain. The results indicated that CPF produced no change in GSH level. Whereas, treatment with either BSO or IR, produced decrease in GSH level. NAC restored GSH level near the control level in all treated groups CPF had no effect on GST activity and pretreatment with either BSO or NAC increased GST activity in CPF treated groups. Also, exposure to IR had no effect on GST activity. Whereas, IR in combination with CPF and/or NAC and/or BSO produced inhibition in plasma GST activity and increased liver GST activity. In addition, both CPF and IR had no effect on the activity of GR. Whereas, pre-treatment with either BSO or NAC produced inhibition in plasma and liver GR activity in CPF treated groups. No change had observed in the IR exposed groups. Treatment with CPF inhibited AChE activity in plasma, liver and brain. Whereas, exposure to IR inhibited AChE activity in brain only

  10. 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.

  11. Activity and stability of a <PON>> oxynitride in the dehydrogenation of isobutane

    Energy Technology Data Exchange (ETDEWEB)

    Delsarte, S.; Grange, P. [Univ. Catholique de Louvain (Belgium). Unite de Catalyse et Chimie des Materiaux Divises; Laurent, Y. [Lab. de Chimie des Materiaux, Univ. de Rennes 1, Rennes (France)

    2000-07-01

    Isobutane dehydrogenation was studied on platinum impregnated mixed aluminium gallium phosphorus oxide and oxynitride, in a continuous, flow micro-reactor at 500-550 C. Comparison of the <> and <PON>> shows the importance of nitridation on the acido-basic properties of the catalyst. A deactivation of the catalyst, due to the deposition of carbonaceous species on the surface, was observed. As the properties of the oxynitride would be altered by a regeneration treatment at high temperature with flowing oxygen, the possibility of decreasing the deactivation rate by decreasing the reaction temperature and by adding hydrogen to the reactant mixture was explored. Catalytic tests, carried out at different hydrogen partial pressures, showed that the hydrogen inhibits the carbon deposition on the surface of the catalyst and thus increases the catalytic stability. (orig.)

  12. Conventional Physics can Explain Excess Heat in the Fleischmann-Pons Cold Fusion Effect

    Science.gov (United States)

    Chubb, Scott

    2011-03-01

    In 1989, when Fleischmann and Pons (FP) claimed they had created room temperature, nuclear fusion in a solid, a firestorm of controversy erupted. Beginning in 1991, the Office of Naval Research began a decade-long study of the FP excess heat effect. This effort documented the fact that the excess heat that FP observed is the result of a form of nuclear fusion that can occur in solids at reduced temperature, dynamically, through a deuteron (d)+d?helium-4 reaction, without high-energy particles or ? rays. This fact has been confirmed at SRI and at a number of other laboratories (most notably in the laboratory of Y. Arata, located at Osaka University, Japan). A key reason this fact has not been accepted is the lack of a cogent argument, based on fundamental physical ideas, justifying it. In the paper, this question is re-examined, based on a generalization of conventional energy band theory that applies to finite, periodic solids, in which d's are allowed to occupy wave-like, ion band states, similar to the kinds of states that electrons occupy in ordinary metals. Prior to being experimentally observed, the Ion Band State Theory of cold fusion predicted a potential d+d?helium-4 reaction, without high energy particles, would explain the excess heat, the helium-4 would be found in an unexpected place (outside heat- producing electrodes), and high-loading, x?1, in PdDx, would be required.

  13. Plane of nutrition during the preweaned period and Mannheimia haemolytica dose influence metabolic responses in post-weaned Holstein calves challenged with bovine herpesvirus-1 and Mannheimia haemolytica

    Science.gov (United States)

    To determine whether previous plane of milk replacer nutrition (PON) and M. haemolytica (MH) dose influences metabolic responses to a combined viral-bacterial respiratory challenge, Holstein calves (1 day of age; n=30) were assigned to treatments in a 2 x 3 factorial with preweaned PON and dose of M...

  14. Plane of nutrition during the preweaned period and Mannheimia haemolytica dose influences inflammatory responses to a combined bovine herpesvirus-1 and Mannheimia haemolytica challenge in post-weaned Holstein calves

    Science.gov (United States)

    To determine whether previous plane of milk replacer nutrition (PON) and M. haemolytica (MH) dose influences inflammatory responses to a combined viral-bacterial respiratory challenge, Holstein calves (1 day of age; n=30) were assigned to treatments in a 2 x 3 factorial with preweaned PON and dose o...

  15. STEREOLOGICAL ANALYSIS OF THE HUMAN PONS VASCULAR NETWORK

    Directory of Open Access Journals (Sweden)

    Ivan Jovanović

    2003-04-01

    Full Text Available Liver is the largest parenchymatous organ, well vascularized, weighing approximately 1.8-3.0% of the whole body weight. Among all abdominal traumas liver injuries account for 25%. For more serious liver injuries the mortality is around 40% in children below 10 years of age. For lesions of the juxtahepatic veins (three major hepatic veins or the retrohepatic portion of v. cava or for complex, combined intra abdominal injuries, the mortality is even up to 70%.This work analyzed the period 1988-2000 during which there were 19 children admitted and treated for blunt liver injuries at the Clinic of Pediatric Surgery and Orthopedics in Nis; I, II and III scale injuries prevailed (17 cases; 89.4%. These injuries were surgically treated for the most part (17 cases; 89.4%. In 7 children (36.8% there were combined injuries. The lethality was 26.3%-5 cases, with three major complications: two intrahepatic hematomas and one biliary fistula associated with biliary peritonitis and biloma formation.

  16. Magnetic Resonance and Spectroscopy of the Human Brain in Gulf War Illness

    National Research Council Canada - National Science Library

    Weiner, Michael

    2004-01-01

    The goal of this project is to test the hypotheses that: 1) Subjects with GWI have reduced NAA in the basal ganglia and pons, which are not accounted for by confounds such as PTSD, depression, and alcohol abuse. 2...

  17. Regional brain distribution of toluene in rats and in a human autopsy

    Energy Technology Data Exchange (ETDEWEB)

    Ameno, Kiyoshi; Kiriu, Takahiro; Fuke, Chiaki; Ameno, Setsuko; Shinohara, Toyohiko; Ijiri, Iwao (Kagawa Medical School (Japan). Dept. of Forensic Medicine)

    1992-02-01

    Toluene concentrations in 9 brain regions of acutely exposed rats and that in 11 brain regions of a human case who inhaled toluene prior to death are described. After exposure to toluene by inhalation (2000 or 10 000 ppm) for 0.5 h or by oral dosing (400 mg/kg.), rats were killed by decapitation 0.5 and 4 h after onset of inhalation and 2 and 10 h after oral ingestion. After each experimental condition the highest range of brain region/blood toluene concentration ratio (BBCR) was in the brain stem regions (2.85-3.22) such as the pons and medulla oblongata, the middle range (1.77-2.12) in the midbrain, thalamus, caudate-putamen, hypothalamus and cerebellum, and the lowest range (1.22-1.64) in the hippocampus and cerebral cortex. These distribution patterns were quite constant. Toluene concentration in various brain regions were unevenly distributed and directly related blood levels. In a human case who had inhaled toluene vapor, the distribution among brain regions was relatively similar to that in rats, the highest concentration ratios being in the corpus callosum (BBCR:2.66) and the lowest in the hippocampus (BBCR:1.47). (orig.).

  18. Magnetic Resonance and Spectroscopy of the Human Brain in Gulf War Illness

    National Research Council Canada - National Science Library

    Weiner, Michael

    2003-01-01

    The goal of this project is to test the hypotheses that: 1.) Subjects with GWI have reduced NAA in the basal ganglia and pons, which are not accounted for by confounds such as depression, post traumatic stress disorder, and alcoholism. 2...

  19. Widely scattered CT lesions in the midbrain and the pons in a case of neuro-Behcet's syndrome

    International Nuclear Information System (INIS)

    Kuroiwa, Yoshiyuki; Tohgi, Hideo; Kanayama, Hiroumi; Fujimori, Masaki; Aoki, Hidehiko

    1985-01-01

    We report on a 30-year-old man with neuro-Behcet's disease. His main neurologic symptoms and signs included headache, alternating hemiparesis, dysarthria, and truncal ataxia. Lumbar puncture demonstrated an elevated pressure, pleocytosis, and an increased protein concentration. Intravenous betamethasone produced a rapid and sustained improvement, without recurrence for two years. Widely scattered foci of small, low-density lesions were disclosed in the midbrain and the pons on a cranial CT scan with 2.5 mm thin-cut slices to enable us to focus on the brainstem. Such CT lesions are consistent with the neuropathological features of this illness, which shows a tendency for brainstem lesions to predominate; these lesions probably represent necrotic areas secondary to vasculitis. Brainstem CT studies with thin-cut slices may be an important diagnostic aid in patients suspected of having neuro-Behcet's disease. (author)

  20. Bandwidth efficient bidirectional 5 Gb/s overlapped-SCM WDM PON with electronic equalization and forward-error correction.

    Science.gov (United States)

    Buset, Jonathan M; El-Sahn, Ziad A; Plant, David V

    2012-06-18

    We demonstrate an improved overlapped-subcarrier multiplexed (O-SCM) WDM PON architecture transmitting over a single feeder using cost sensitive intensity modulation/direct detection transceivers, data re-modulation and simple electronics. Incorporating electronic equalization and Reed-Solomon forward-error correction codes helps to overcome the bandwidth limitation of a remotely seeded reflective semiconductor optical amplifier (RSOA)-based ONU transmitter. The O-SCM architecture yields greater spectral efficiency and higher bit rates than many other SCM techniques while maintaining resilience to upstream impairments. We demonstrate full-duplex 5 Gb/s transmission over 20 km and analyze BER performance as a function of transmitted and received power. The architecture provides flexibility to network operators by relaxing common design constraints and enabling full-duplex operation at BER ∼ 10(-10) over a wide range of OLT launch powers from 3.5 to 8 dBm.

  1. Hepatopancreatic intoxication of lambda cyhalothrin insecticide on albino rats.

    Science.gov (United States)

    Elhalwagy, Manal Ea; Abd-Alrahman, Sherif H; Nahas, A A; Ziada, Reem M; Mohamady, Aziza H

    2015-01-01

    Despite the known adverse effects of lambda cyhalothrin insecticide, little is known about its hepatopancreatic intoxication effects. The present study was carried out to elucidate sub-chronic effect of Karat 2.5% EC formulation of lambda cyhalothrin on male albino rats. To explore the effects of exposure to lambda cyhalothrin on rats and its mechanism, low (1/40 of LD50, 5 mg/kg/day) and high dose (1/4 of LD50, 50 mg/kg/day) lambda cyhalothrin were applied to rats via drinking water for 3 months. Blood samples were collected monthly, and the animals were dissected for liver and pancreas's examination at the end of the experiment. Lambda cyhalothrin administration was associated with the elevation in lipid peroxidation marker, malondialdehyde (MDA), reduction in SH-protein a major marker for antioxidant, as well as basel paraoxonase (PON) in both treated groups throughout the experimental periods. In addition, significant elevations in liver enzymes alanin amino transferase, (ALT), and aspartate amino transferase (AST), as well as plasma acetylcholinesterase (AChE) and glucose level. While, significant reduction in insulin level through the experimental periods. Results of histopathological and histochemical studies showed that lambda cyhalothrin exposure induces liver and pancreatic tissues damage and depletion in glycogen content was pronounced in liver of both treated groups. In conclusion subchronic intoxication with lambda cyhalothrin formulation induced remarkable changes in the examined parameters.

  2. Novel WRM-based architecture of hybrid PON featuring online access and full-fiber-fault protection for smart grid

    Science.gov (United States)

    Li, Xingfeng; Gan, Chaoqin; Liu, Zongkang; Yan, Yuqi; Qiao, HuBao

    2018-01-01

    In this paper, a novel architecture of hybrid PON for smart grid is proposed by introducing a wavelength-routing module (WRM). By using conventional optical passive components, a WRM with M ports is designed. The symmetry and passivity of the WRM makes it be easily integrated and very cheap in practice. Via the WRM, two types of network based on different ONU-interconnected manner can realize online access. Depending on optical switches and interconnecting fibers, full-fiber-fault protection and dynamic bandwidth allocation are realized in these networks. With the help of amplitude modulation, DPSK modulation and RSOA technology, wavelength triple-reuse is achieved. By means of injecting signals into left and right branches in access ring simultaneously, the transmission delay is decreased. Finally, the performance analysis and simulation of the network verifies the feasibility of the proposed architecture.

  3. Full-asynchronous gigabit-symmetric DPSK downstream and OOK upstream OCDMA-PON with source-free ONUs employing all-optical self-clocked time gate.

    Science.gov (United States)

    Dai, Bo; Shimizu, Satoshi; Wang, Xu; Wada, Naoya

    2012-12-10

    We propose an asynchronous gigabit-symmetric optical code division multiplexing access passive optical network (OCDMA-PON) in which optical network units (ONUs) are source-free. In the experiment, we demonstrate a duplex OCDMA system with a 50 km 10 Gbit/s/user 4-user DPSK-OCDMA downlink and a 50 km 10 Gbit/s/user 4-user OOK-OCDMA uplink and error-free duplex transmissions are achieved. Besides, we investigate an all-optical self-clocked time gate, which is used for the signal regeneration of decoded signals and ensures asynchronization in the up/downstream transmissions. Furthermore, we evaluate the power budget of the proposed duplex transmission.

  4. Somatotopic arrangement and location of the corticospinal tract in the brainstem of the human brain.

    Science.gov (United States)

    Jang, Sung Ho

    2011-07-01

    The corticospinal tract (CST) is the most important motor pathway in the human brain. Detailed knowledge of CST somatotopy is important in terms of rehabilitative management and invasive procedures for patients with brain injuries. In this study, I conducted a review of nine previous studies of the somatotopical location and arrangement at the brainstem in the human brain. The results of this review indicated that the hand and leg somatotopies of the CST are arranged medio-laterally in the mid to lateral portion of the cerebral peduncle, ventromedial-dorsolaterally in the pontine basis, and medio-laterally in the medullary pyramid. However, few diffusion tensor imaging (DTI) studies have been conducted on this topic, and only nine have been reported: midbrain (2 studies), pons (4 studies), and medulla (1 study). Therefore, further DTI studies should be conducted in order to expand the literature on this topic. In particular, research on midbrain and medulla should be encouraged.

  5. All-optical VPN utilizing DSP-based digital orthogonal filters access for PONs

    Science.gov (United States)

    Zhang, Xiaoling; Zhang, Chongfu; Chen, Chen; Jin, Wei; Qiu, Kun

    2018-04-01

    Utilizing digital filtering-enabled signal multiplexing and de-multiplexing, a cost-effective all-optical virtual private network (VPN) system is proposed, for the first time to our best knowledge, in digital filter multiple access passive optical networks (DFMA-PONs). Based on the DFMA technology, the proposed system can be easily designed to meet the requirements of next generation network's flexibility, elasticity, adaptability and compatibility. Through dynamic digital filter allocation and recycling, the proposed all-optical VPN system can provide dynamic establishments and cancellations of multiple VPN communications with arbitrary traffic volumes. More importantly, due to the employment of DFMA technology, the system is not limited to a fixed signal format and different signal formats such as pulse amplitude modulation (PAM), quadrature amplitude modulation (QAM) and orthogonal frequency division multiplexing (OFDM) can be used. Moreover, one transceiver is sufficient to simultaneously transmit upstream (US)/VPN data to optical line terminal (OLT) or other VPN optical network units (ONUs), thus leading to great reduction in network constructions and operation expenditures. The proposed all-optical VPN system is demonstrated with the transceiver incorporating the formats of QAM and OFDM, which can be made transparent to downstream (DS), US and VPN communications. The bit error rates (BERs) of DS, US and VPN for OFDM signals are below the forward-error-correction (FEC) limit of 3 . 8 × 10-3 when the received optical powers are about -16.8 dBm, -14.5 dBm and -15.7 dBm, respectively.

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

    African Journals Online (AJOL)

    Nadia Youssef Sadek Morcos

    2015-03-31

    Mar 31, 2015 ... toxicity primarily by inhibiting the enzyme acetylcholinesterase. (AChE) [1]. ... 3. Methods. DNA was extracted from whole blood using a QIAamp Blood .... activity. It is not clear whether this is because of a decreased stability of ...

  7. Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent.

    Science.gov (United States)

    Roberts, D R; Chatterjee, A R; Yazdani, M; Marebwa, B; Brown, T; Collins, H; Bolles, G; Jenrette, J M; Nietert, P J; Zhu, X

    2016-12-01

    While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus. We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations. During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (r s = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in

  8. Brain metabolite changes on proton magnetic resonance spectroscopy in children with poorly controlled type 1 diabetes mellitus

    International Nuclear Information System (INIS)

    Sarac, K.; Alkan, A.; Baysal, T.; Akinci, A.; Aslan, M.; Oezcan, C.

    2005-01-01

    The metabolite changes in the brains of children with poorly controlled type 1 diabetes mellitus (DM) were investigated by proton magnetic resonance spectroscopy (MRS). A total of 30 subjects and 14 age-matched healthy volunteers underwent single-voxel MRS (TE: 136). The duration of disease, medication, presence of hypoglycaemia episodes and the level of haemoglobin A1C (HbA1C) in the patients were noted. Voxels were placed in the pons, left basal ganglion (LBG) and left posterior parietal white matter (PPWM). N-acetylaspartate (NAA)/creatinine (Cr) and choline (Cho)/Cr ratios were calculated. The average HbA1c level was 11.9±3.4 (8.2-19.4). The average number of keto-acidosis episodes was 1.9±2.2 (0-9) and the average number of daily insulin injections was 2.8±0.97 (2-4). MRS revealed lower NAA/Cr and Cho/Cr ratios in the pons and lower NAA/Cr ratio in the PPWM of patients with DM than in control subjects. No significant correlation was observed between the number of hypoglycaemia episodes and metabolite ratios. Metabolic abnormalities have been observed by MRS in the brain of poorly controlled type 1 DM children. These metabolic changes, in particular in the pons region, include a decrease in NAA, indicating neuronal loss or functional impairment, and likely explanations for a decrease in Cho may be dynamic changes in membrane lipids and/or decreased membrane turnover. (orig.)

  9. Brain metabolite changes on proton magnetic resonance spectroscopy in children with poorly controlled type 1 diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Sarac, K.; Alkan, A.; Baysal, T. [Inonu University School of Medicine, Department of Radiology, Malatya (Turkey); Akinci, A.; Aslan, M. [Inonu University School of Medicine, Department of Paediatric Endocrinology, Malatya (Turkey); Oezcan, C. [Inonu University School of Medicine, Department of Neurology, Malatya (Turkey)

    2005-07-01

    The metabolite changes in the brains of children with poorly controlled type 1 diabetes mellitus (DM) were investigated by proton magnetic resonance spectroscopy (MRS). A total of 30 subjects and 14 age-matched healthy volunteers underwent single-voxel MRS (TE: 136). The duration of disease, medication, presence of hypoglycaemia episodes and the level of haemoglobin A1C (HbA1C) in the patients were noted. Voxels were placed in the pons, left basal ganglion (LBG) and left posterior parietal white matter (PPWM). N-acetylaspartate (NAA)/creatinine (Cr) and choline (Cho)/Cr ratios were calculated. The average HbA1c level was 11.9{+-}3.4 (8.2-19.4). The average number of keto-acidosis episodes was 1.9{+-}2.2 (0-9) and the average number of daily insulin injections was 2.8{+-}0.97 (2-4). MRS revealed lower NAA/Cr and Cho/Cr ratios in the pons and lower NAA/Cr ratio in the PPWM of patients with DM than in control subjects. No significant correlation was observed between the number of hypoglycaemia episodes and metabolite ratios. Metabolic abnormalities have been observed by MRS in the brain of poorly controlled type 1 DM children. These metabolic changes, in particular in the pons region, include a decrease in NAA, indicating neuronal loss or functional impairment, and likely explanations for a decrease in Cho may be dynamic changes in membrane lipids and/or decreased membrane turnover. (orig.)

  10. Návrh a simulace optické přístupové sítě typu PON

    OpenAIRE

    Mikauš, Jiří

    2012-01-01

    Cílem diplomové práce bylo demonstrovat zvolenou PON sít v simulačním nástroji OPNET Modeler. Práce se věnuje pasivním optickým sítím. Zejména pak řešením, která jsou založená na přenosu Ethernet rámců. V teoretické části jsou popsány standardy EPON a 10GEPON. Standard EPON byl představen již v roce 2004. Novější 10GEPON je zpětně plně kompatibilní, což jej předurčuje jako vhodné řešení pro moderní sítě s vyšším nárokem na přenosové rychlosti. V praktické části je popsán postup při tvorbě síť...

  11. [18F]Fluoroethylflumazenil: a novel tracer for PET imaging of human benzodiazepine receptors

    International Nuclear Information System (INIS)

    Gruender, G.; Lange-Asschenfeldt, C.; Vernaleken, I.; Lueddens, H.; Siessmeier, T.; Buchholz, H.-G.; Bartenstein, P.; Stoeter, P.; Drzezga, A.; Roesch, F.

    2001-01-01

    5-(2'-[ 18 F]Fluoroethyl)flumazenil ([ 18 F]FEF) is a fluorine-18 labelled positron emission tomography (PET) tracer for central benzodiazepine receptors. Compared with the established [ 11 C]flumazenil, it has the advantage of the longer half-life of the fluorine-18 label. After optimisation of its synthesis and determination of its in vitro receptor affinities, we performed first PET studies in humans. PET studies in seven healthy human volunteers were performed on a Siemens ECAT EXACT whole-body scanner after injection of 100-280 MBq [ 18 F]FEF. In two subjects, a second PET scan was conducted after pretreatment with unlabelled flumazenil (1 mg or 2.5 mg i.v., 3 min before tracer injection). A third subject was studied both with [ 18 F]FEF and with [ 11 C]flumazenil. Brain radioactivity was measured for 60-90 min p.i. and analysed with a region of interest-oriented approach and on a voxelwise basis with spectral analysis. Plasma radioactivity was determined from arterial blood samples and metabolites were determined by high-performance liquid chromatography. In human brain, maximum radioactivity accumulation was observed 4±2 min p.i., with a fast clearance kinetics resulting in 50% and 20% of maximal activities at about 10 and 30 min, respectively. [ 18 F]FEF uptake followed the known central benzodiazepine receptor distribution in the human brain (occipital cortex >temporal cortex >cerebellum >thalamus >pons). Pretreatment with unlabelled flumazenil resulted in reduced tracer uptake in all brain areas except for receptor-free reference regions like the pons. Parametric images of distribution volume and binding potential generated on a voxelwise basis revealed two- to three-fold lower in vivo receptor binding of [ 18 F]FEF compared with [ 11 C]flumazenil, while relative uptake of [ 18 F]FEF was higher in the cerebellum, most likely owing to its relatively higher affinity for benzodiazepine receptors containing the α6 subunit. Metabolism of [ 18 F]FEF was very

  12. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

    International Nuclear Information System (INIS)

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos; Knowlton, Caitlin; Kim, Baek; Sawyer, Sara L.; Diaz-Griffero, Felipe

    2014-01-01

    SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs

  13. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

    Energy Technology Data Exchange (ETDEWEB)

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States); Knowlton, Caitlin; Kim, Baek [Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States); Sawyer, Sara L. [Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712 (United States); Diaz-Griffero, Felipe, E-mail: Felipe.Diaz-Griffero@einstein.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States)

    2014-07-15

    SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs.

  14. Hypolipidemic, antioxidant and antiatherogenic property of sardine by-products proteins in high-fat diet induced obese rats.

    Science.gov (United States)

    Affane, Fouad; Louala, Sabrine; El Imane Harrat, Nour; Bensalah, Fatima; Chekkal, Hadjera; Allaoui, Amine; Lamri-Senhadji, Myriem

    2018-04-15

    Fish by-products valorization on account of their richness in bioactive compounds may represent a better alternative to marine products with a view to economic profitability and sustainable development. In this study, we compared the effect of sardine by-product proteins (SBy-P), with those of the fillets (SF-P) or casein (Cas), on growth parameters, serum leptin level, lipids disorders, lipid peroxidation and reverse cholesterol transport, in diet-induced obese rats. Obesity was induced by feeding rats a high-fat diet (20% sheep fat), during 12 weeks. At body weight (BW) of 400 ± 20 g, eighteen obese rats were divided into three homogenous groups and continue to consume the high-fat diet for 4 weeks containing either, 20% SBy-P, SF-P or Cas. The results showed that SBy-P, compared to SF-P and Cas, efficiently reduced food intake (FI), BW gain and serum leptin level, and improved blood lipids levels and reverse cholesterol transport by reducing total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-HDL 1 -C) serum levels, increasing the level of high-density lipoprotein cholesterol (HDL 2 -C and HDL 3 -C), and enhancing lecithin: cholesterol acyltransferase (LCAT) activity. Furthermore, they attenuated lipid peroxidation by increasing atheroprotective activity of the paraoxonase-1 (PON-1). Sardine by-product proteins due to their richness in certain essential amino acids, highlight weight-loss, lipid-lowering, antioxidant and anti-atherogenic potentials, contributing to the improvement of the complications associated with obesity. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Melatonin mitigates thioacetamide-induced hepatic fibrosis via antioxidant activity and modulation of proinflammatory cytokines and fibrogenic genes.

    Science.gov (United States)

    Lebda, Mohamed A; Sadek, Kadry M; Abouzed, Tarek K; Tohamy, Hossam G; El-Sayed, Yasser S

    2018-01-01

    The potential antifibrotic effects of melatonin against induced hepatic fibrosis were explored. Rats were allocated into four groups: placebo; thioacetamide (TAA) (200mg/kg bwt, i.p twice weekly for two months); melatonin (5mg/kgbwt, i.p daily for a week before TAA and continued for an additional two months); and melatonin plus TAA. Hepatic fibrotic changes were evaluated biochemically and histopathologically. Hepatic oxidative/antioxidative indices were assessed. The expression of hepatic proinflammatory cytokines (tumor necrosis factor-α, and interleukin-1β), fibrogenic-related genes (transforming growth factor-1β, collagen I, collagen, III, laminin, and autotaxin) and an antioxidant-related gene (thioredoxin-1) were detected by qRT-PCR. In fibrotic rats, melatonin lowered serum aspartate aminotransferase, alanine aminotransferase, and autotaxin activities, bilirubin, hepatic hydroxyproline and plasma ammonia levels. Melatonin displayed hepatoprotective and antifibrotic potential as indicated by mild hydropic degeneration of some hepatocytes and mild fibroplasia. In addition, TAA induced the depletion of glutathione, glutathione s-transferase, glutathione peroxidase, superoxide dismutase, catalase, and paraoxonase-1 (PON-1), while inducing the accumulation of malondialdehyde, protein carbonyl (C=O) and nitric oxide (NO), and DNA fragmentation. These effects were restored by melatonin pretreatment. Furthermore, melatonin markedly attenuated the expression of proinflammatory cytokines and fibrogenic genes via the upregulation of thioredoxin-1 mRNA transcripts. Melatonin exhibits potent anti-inflammatory, antioxidant and fibrosuppressive activities against TAA-induced hepatic fibrogenesis via the suppression of oxidative stress, DNA damage, proinflammatory cytokines and fibrogenic gene transcripts. In addition, we demonstrate that the antifibrotic activity of melatonin is mediated by the induction of thioredoxin-1 with attenuation of autotaxin expressions

  16. Expression and function of human hemokinin-1 in human and guinea pig airways.

    Science.gov (United States)

    Grassin-Delyle, Stanislas; Naline, Emmanuel; Buenestado, Amparo; Risse, Paul-André; Sage, Edouard; Advenier, Charles; Devillier, Philippe

    2010-10-07

    Human hemokinin-1 (hHK-1) and endokinins are peptides of the tachykinin family encoded by the TAC4 gene. TAC4 and hHK-1 expression as well as effects of hHK-1 in the lung and airways remain however unknown and were explored in this study. RT-PCR analysis was performed on human bronchi to assess expression of tachykinin and tachykinin receptors genes. Enzyme immunoassay was used to quantify hHK-1, and effects of hHK-1 and endokinins on contraction of human and guinea pig airways were then evaluated, as well as the role of hHK-1 on cytokines production by human lung parenchyma or bronchi explants and by lung macrophages. In human bronchi, expression of the genes that encode for hHK-1, tachykinin NK1-and NK2-receptors was demonstrated. hHK-1 protein was found in supernatants from explants of human bronchi, lung parenchyma and lung macrophages. Exogenous hHK-1 caused a contractile response in human bronchi mainly through the activation of NK2-receptors, which blockade unmasked a NK1-receptor involvement, subject to a rapid desensitization. In the guinea pig trachea, hHK-1 caused a concentration-dependant contraction mainly mediated through the activation of NK1-receptors. Endokinin A/B exerted similar effects to hHK-1 on both human bronchi and guinea pig trachea, whereas endokinins C and D were inactive. hHK-1 had no impact on the production of cytokines by explants of human bronchi or lung parenchyma, or by human lung macrophages. We demonstrate endogenous expression of TAC4 in human bronchi, the encoded peptide hHK-1 being expressed and involved in contraction of human and guinea pig airways.

  17. Expression and function of human hemokinin-1 in human and guinea pig airways

    Directory of Open Access Journals (Sweden)

    Sage Edouard

    2010-10-01

    Full Text Available Abstract Background Human hemokinin-1 (hHK-1 and endokinins are peptides of the tachykinin family encoded by the TAC4 gene. TAC4 and hHK-1 expression as well as effects of hHK-1 in the lung and airways remain however unknown and were explored in this study. Methods RT-PCR analysis was performed on human bronchi to assess expression of tachykinin and tachykinin receptors genes. Enzyme immunoassay was used to quantify hHK-1, and effects of hHK-1 and endokinins on contraction of human and guinea pig airways were then evaluated, as well as the role of hHK-1 on cytokines production by human lung parenchyma or bronchi explants and by lung macrophages. Results In human bronchi, expression of the genes that encode for hHK-1, tachykinin NK1-and NK2-receptors was demonstrated. hHK-1 protein was found in supernatants from explants of human bronchi, lung parenchyma and lung macrophages. Exogenous hHK-1 caused a contractile response in human bronchi mainly through the activation of NK2-receptors, which blockade unmasked a NK1-receptor involvement, subject to a rapid desensitization. In the guinea pig trachea, hHK-1 caused a concentration-dependant contraction mainly mediated through the activation of NK1-receptors. Endokinin A/B exerted similar effects to hHK-1 on both human bronchi and guinea pig trachea, whereas endokinins C and D were inactive. hHK-1 had no impact on the production of cytokines by explants of human bronchi or lung parenchyma, or by human lung macrophages. Conclusions We demonstrate endogenous expression of TAC4 in human bronchi, the encoded peptide hHK-1 being expressed and involved in contraction of human and guinea pig airways.

  18. Real time 1.55 μm VCSEL-based coherent detection link

    DEFF Research Database (Denmark)

    Rodes Lopez, Roberto; Parekh, D.; Jensen, Jesper Bevensee

    2012-01-01

    This paper presents an experimental demonstration of VCSEL-based PON with simplified real-time coherent receiver at 2.5 Gbps. Receiver sensitivity of −37 dBm is achieved proving splitting ratio up to 2048 after 17 km fiber transmission.......This paper presents an experimental demonstration of VCSEL-based PON with simplified real-time coherent receiver at 2.5 Gbps. Receiver sensitivity of −37 dBm is achieved proving splitting ratio up to 2048 after 17 km fiber transmission....

  19. CYP1A1 and CYP1A2 expression: Comparing 'humanized' mouse lines and wild-type mice; comparing human and mouse hepatoma-derived cell lines

    International Nuclear Information System (INIS)

    Uno, Shigeyuki; Endo, Kaori; Ishida, Yuji; Tateno, Chise; Makishima, Makoto; Yoshizato, Katsutoshi; Nebert, Daniel W.

    2009-01-01

    Human and rodent cytochrome P450 (CYP) enzymes sometimes exhibit striking species-specific differences in substrate preference and rate of metabolism. Human risk assessment of CYP substrates might therefore best be evaluated in the intact mouse by replacing mouse Cyp genes with human CYP orthologs; however, how 'human-like' can human gene expression be expected in mouse tissues? Previously a bacterial-artificial-chromosome-transgenic mouse, carrying the human CYP1A1 C YP1A2 locus and lacking the mouse Cyp1a1 and Cyp1a2 orthologs, was shown to express robustly human dioxin-inducible CYP1A1 and basal versus inducible CYP1A2 (mRNAs, proteins, enzyme activities) in each of nine mouse tissues examined. Chimeric mice carrying humanized liver have also been generated, by transplanting human hepatocytes into a urokinase-type plasminogen activator(+/+) s evere-combined-immunodeficiency (uPA/SCID) line with most of its mouse hepatocytes ablated. Herein we compare basal and dioxin-induced CYP1A mRNA copy numbers, protein levels, and four enzymes (benzo[a]pyrene hydroxylase, ethoxyresorufin O-deethylase, acetanilide 4-hydroxylase, methoxyresorufin O-demethylase) in liver of these two humanized mouse lines versus wild-type mice; we also compare these same parameters in mouse Hepa-1c1c7 and human HepG2 hepatoma-derived established cell lines. Most strikingly, mouse liver CYP1A1-specific enzyme activities are between 38- and 170-fold higher than human CYP1A1-specific enzyme activities (per unit of mRNA), whereas mouse versus human CYP1A2 enzyme activities (per unit of mRNA) are within 2.5-fold of one another. Moreover, both the mouse and human hepatoma cell lines exhibit striking differences in CYP1A mRNA levels and enzyme activities. These findings are relevant to risk assessment involving human CYP1A1 and CYP1A2 substrates, when administered to mice as environmental toxicants or drugs.

  20. Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

    OpenAIRE

    Jiae Kim; Jiae Kim; Kristina K. Peachman; Kristina K. Peachman; Ousman Jobe; Ousman Jobe; Elaine B. Morrison; Atef Allam; Atef Allam; Linda Jagodzinski; Sofia A. Casares; Mangala Rao

    2017-01-01

    Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP) models for studying human immunodeficiency virus (HIV)-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several...

  1. Análisis de prestaciones de láseres en redes de acceso ópticas pasivas de siguiente generación NG-PON2 (Next Generation Passive Optical Networks)

    OpenAIRE

    Martín González, Daniel

    2017-01-01

    Este trabajo se centra en el estudio a nivel físico de las redes ópticas de acceso de siguiente generación (NG-PON2, Next Generation Passive Optical Networks), con las que se llegan a conseguir velocidades de transmisión de datos no inferiores a 40Gbits/s. Esto es gracias a la introducción de 4 longitudes de onda en cada sentido de transmisión. Además, estas redes tienen la ventaja añadida de conseguir transmisiones entre el OLT (Optical Line Termination) y las ONUs (Optical Network Units) de...

  2. Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

    Science.gov (United States)

    Kim, Jiae; Peachman, Kristina K.; Jobe, Ousman; Morrison, Elaine B.; Allam, Atef; Jagodzinski, Linda; Casares, Sofia A.; Rao, Mangala

    2017-01-01

    Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP) models for studying human immunodeficiency virus (HIV)-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several different types of humanized mice have been developed with varying levels of reconstitution of human CD45+ cells. In this study, we utilized humanized Rag1KO.IL2RγcKO.NOD mice expressing HLA class II (DR4) molecule (DRAG mice) infused with HLA-matched hematopoietic stem cells from umbilical cord blood to study early events after HIV-1 infection, since the mucosal tissues of these mice are highly enriched for human lymphocytes and express the receptors and coreceptors needed for HIV-1 entry. We examined the various tissues on days 4, 7, 14, and 21 after an intravaginal administration of a single dose of purified primary HIV-1. Plasma HIV-1 RNA was detected as early as day 7, with 100% of the animals becoming plasma RNA positive by day 21 post-infection. Single cells were isolated from lymph nodes, bone marrow, spleen, gut, female reproductive tissue, and brain and analyzed for gag RNA and strong stop DNA by quantitative (RT)-PCR. Our data demonstrated the presence of HIV-1 viral RNA and DNA in all of the tissues examined and that the virus was replication competent and spread rapidly. Bone marrow, gut, and lymph nodes were viral RNA positive by day 4 post-infection, while other tissues and plasma became positive typically between 7 and 14 days post-infection. Interestingly, the brain was the last tissue to become HIV-1 viral RNA and DNA positive by day 21 post-infection. These data support the notion that humanized DRAG mice could serve as an excellent model for studying the

  3. Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

    Directory of Open Access Journals (Sweden)

    Jiae Kim

    2017-10-01

    Full Text Available Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP models for studying human immunodeficiency virus (HIV-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several different types of humanized mice have been developed with varying levels of reconstitution of human CD45+ cells. In this study, we utilized humanized Rag1KO.IL2RγcKO.NOD mice expressing HLA class II (DR4 molecule (DRAG mice infused with HLA-matched hematopoietic stem cells from umbilical cord blood to study early events after HIV-1 infection, since the mucosal tissues of these mice are highly enriched for human lymphocytes and express the receptors and coreceptors needed for HIV-1 entry. We examined the various tissues on days 4, 7, 14, and 21 after an intravaginal administration of a single dose of purified primary HIV-1. Plasma HIV-1 RNA was detected as early as day 7, with 100% of the animals becoming plasma RNA positive by day 21 post-infection. Single cells were isolated from lymph nodes, bone marrow, spleen, gut, female reproductive tissue, and brain and analyzed for gag RNA and strong stop DNA by quantitative (RT-PCR. Our data demonstrated the presence of HIV-1 viral RNA and DNA in all of the tissues examined and that the virus was replication competent and spread rapidly. Bone marrow, gut, and lymph nodes were viral RNA positive by day 4 post-infection, while other tissues and plasma became positive typically between 7 and 14 days post-infection. Interestingly, the brain was the last tissue to become HIV-1 viral RNA and DNA positive by day 21 post-infection. These data support the notion that humanized DRAG mice could serve as an excellent model

  4. Quantification of hydrolysis of toxic organophosphates and organophosphonates by diisopropyl fluorophosphatase from Loligo vulgaris by in situ Fourier transform infrared spectroscopy.

    Science.gov (United States)

    Gäb, Jürgen; Melzer, Marco; Kehe, Kai; Richardt, André; Blum, Marc-Michael

    2009-02-15

    The enzyme diisopropyl fluorophosphatase (DFPase) from the squid Loligo vulgaris effectively catalyzes the hydrolysis of diisopropyl fluorophosphate (DFP) and a number of organophosphorus nerve agents, including sarin, soman, cyclosarin, and tabun. Up to now, the determination of kinetic data has been achieved by techniques such as pH-stat titration, ion-selective electrodes, and fluorogenic substrate analogs. We report a new assaying method using in situ Fourier transform infrared (FTIR) spectroscopy with attenuated total reflection (ATR) for the real-time determination of reaction rates. The method employs changes in the P-O-R stretching vibration of DFP and nerve agent substrates when hydrolyzed to their corresponding phosphoric and phosphonic acids. It is shown that the Lambert-Beer law holds and that changes in absorbance can be directly related to changes in concentration. Compared with other methods, the use of in situ FTIR spectroscopy results in a substantially reduced reaction volume that adds extra work safety when handling highly toxic substrates. In addition, the new method allows the noninvasive measurement of buffered solutions with varying ionic strengths complementing existing methods. Because the assay is independent of the used enzyme, it should also be applicable to other phosphotriesterase enzymes such as organophosphorus hydrolase (OPH), organophosphorus acid anhydrolase (OPAA), and paraoxonase (PON).

  5. 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

  6. Concentration, composition, bioavailability, and N-nitrosodimethylamine formation potential of particulate and dissolved organic nitrogen in wastewater effluents: A comparative study

    International Nuclear Information System (INIS)

    Hu, Haidong; Ma, Haijun; Ding, Lili; Geng, Jinju; Xu, Ke; Huang, Hui; Zhang, Yingying; Ren, Hongqiang

    2016-01-01

    Wastewater-derived organic nitrogen (org-N) can act as both nutrients and carcinogenic nitrogenous disinfection byproduct precursors. In this study, the concentration, composition, bioavailability, and N-nitrosodimethylamine (NDMA) formation potential of particulate organic nitrogen (PON) from three different municipal wastewater treatment plants were characterized and compared with that of effluent dissolved organic nitrogen (DON). The average effluent PON and DON concentrations ranged from 0.09 to 0.55 mg N/L and from 0.91 to 1.88 mg N/L, respectively. According to principal component analysis, org-N composition and characterization differed in PON and DON samples (n = 20). Compared with DON, PON tended to be enriched in protein and nucleic acids, and showed a more proteinaceous character. Composition of org-N functional groups estimated from the X-ray photoelectron spectroscopy N 1s spectra indicate no significant differences in the molecular weight distribution of the protein-like materials between PON and DON. Moreover, PON exhibited a significantly higher bioavailability (61.0 ± 13.3%) compared to DON (38.5 ± 12.4%, p < 0.05, t-test) and a significantly higher NDMA yields (791.4 ± 404.0 ng/mg-N) compared to DON (374.8 ± 62.5 ng/mg-N, p < 0.05, t-test). Accordingly, PON contributed to approximately 12.3–41.7% of the total bioavailable org-N and 22.0–38.4% of the total NDMA precursors in wastewater effluents. Thus, the potential adverse effects of PON on wastewater discharge and reuse applications should not be overlooked, even though it only accounted for 7.4–26.8% of the total effluent org-N. - Highlights: • The concentration, composition, bioavailability, and NDMA FP of PON and DON in wastewater effluents are compared. • PON is enriched in protein and nucleic acids. • PON is more bioavailable and shows higher NDMA yields compared to DON. • PON contributes12–42% of total bioavailable org-N and 22–38% of total NDMA precursors.

  7. Concentration, composition, bioavailability, and N-nitrosodimethylamine formation potential of particulate and dissolved organic nitrogen in wastewater effluents: A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Haidong; Ma, Haijun; Ding, Lili; Geng, Jinju; Xu, Ke; Huang, Hui; Zhang, Yingying; Ren, Hongqiang, E-mail: hqren@nju.edu.cn

    2016-11-01

    Wastewater-derived organic nitrogen (org-N) can act as both nutrients and carcinogenic nitrogenous disinfection byproduct precursors. In this study, the concentration, composition, bioavailability, and N-nitrosodimethylamine (NDMA) formation potential of particulate organic nitrogen (PON) from three different municipal wastewater treatment plants were characterized and compared with that of effluent dissolved organic nitrogen (DON). The average effluent PON and DON concentrations ranged from 0.09 to 0.55 mg N/L and from 0.91 to 1.88 mg N/L, respectively. According to principal component analysis, org-N composition and characterization differed in PON and DON samples (n = 20). Compared with DON, PON tended to be enriched in protein and nucleic acids, and showed a more proteinaceous character. Composition of org-N functional groups estimated from the X-ray photoelectron spectroscopy N 1s spectra indicate no significant differences in the molecular weight distribution of the protein-like materials between PON and DON. Moreover, PON exhibited a significantly higher bioavailability (61.0 ± 13.3%) compared to DON (38.5 ± 12.4%, p < 0.05, t-test) and a significantly higher NDMA yields (791.4 ± 404.0 ng/mg-N) compared to DON (374.8 ± 62.5 ng/mg-N, p < 0.05, t-test). Accordingly, PON contributed to approximately 12.3–41.7% of the total bioavailable org-N and 22.0–38.4% of the total NDMA precursors in wastewater effluents. Thus, the potential adverse effects of PON on wastewater discharge and reuse applications should not be overlooked, even though it only accounted for 7.4–26.8% of the total effluent org-N. - Highlights: • The concentration, composition, bioavailability, and NDMA FP of PON and DON in wastewater effluents are compared. • PON is enriched in protein and nucleic acids. • PON is more bioavailable and shows higher NDMA yields compared to DON. • PON contributes12–42% of total bioavailable org-N and 22–38% of total NDMA precursors.

  8. DIANA: A Machine Learning Mechanism for Adjusting the TDD Uplink-Downlink Configuration in XG-PON-LTE Systems

    Directory of Open Access Journals (Sweden)

    Panagiotis Sarigiannidis

    2017-01-01

    Full Text Available Modern broadband hybrid optical-wireless access networks have gained the attention of academia and industry due to their strategic advantages (cost-efficiency, huge bandwidth, flexibility, and mobility. At the same time, the proliferation of Software Defined Networking (SDN enables the efficient reconfiguration of the underlying network components dynamically using SDN controllers. Hence, effective traffic-aware schemes are feasible in dynamically determining suitable configuration parameters for advancing the network performance. To this end, a novel machine learning mechanism is proposed for an SDN-enabled hybrid optical-wireless network. The proposed architecture consists of a 10-gigabit-capable passive optical network (XG-PON in the network backhaul and multiple Long Term Evolution (LTE radio access networks in the fronthaul. The proposed mechanism receives traffic-aware knowledge from the SDN controllers and applies an adjustment on the uplink-downlink configuration in the LTE radio communication. This traffic-aware mechanism is capable of determining the most suitable configuration based on the traffic dynamics in the whole hybrid network. The introduced scheme is evaluated in a realistic environment using real traffic traces such as Voice over IP (VoIP, real-time video, and streaming video. According to the obtained numerical results, the proposed mechanism offers significant improvements in the network performance in terms of latency and jitter.

  9. 10 CFR 1.39 - Office of Human Resources.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Office of Human Resources. 1.39 Section 1.39 Energy... § 1.39 Office of Human Resources. The Office of Human Resources— (a) Plans and implements NRC policies... agency's human resources; (b) Provides labor relations and personnel policy guidance and supporting...

  10. Power budget of direct-detection ultra-dense WDM-Nyquist-SCM PON with low-complexity SSBI mitigation

    Science.gov (United States)

    Soeiro, Ricardo O. J.; Alves, Tiago M. F.; Cartaxo, Adolfo V. T.

    2017-07-01

    The power budget (PB) of a direct-detection ultra-dense wavelength division/subcarrier multiplexing (SCM) passive optical network (PON) is assessed numerically for downstream, when a low-complexity iterative signal-to-signal beat interference (SSBI) mitigation technique is employed. Each SCM signal, inserted in a 12.5 GHz width optical channel, is comprised of two or three electrically generated and multiplexed 16-quadrature-amplitude-modulation (QAM) or 32-QAM Nyquist pulse-shaped subcarriers, each with a 7% forward error correction bit rate of 10.7 Gbit/s. The PB and maximum number of optical network units (ONUs) served by each optical line terminal (OLT) are compared with and without SSBI mitigation. When SSBI mitigation is realized, PB gains up to 4.5 dB are attained relative to the PB in the absence of SSBI mitigation. The PB gain enabled by the SSBI mitigation technique proposed in this work increases the number of ONUs served per OLT at least by a factor of 2, for the cases of higher spectral efficiency. In particular, for a SCM signal comprised of three subcarriers, the maximum number of ONUs served per OLT is between 2 and 32, and between 8 and 64, in the absence of SSBI mitigation, and when SSBI mitigation is employed, respectively, depending on the fiber length (up to 50 km) and order of QAM.

  11. Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells

    Directory of Open Access Journals (Sweden)

    Stanislav V. Sosnovtsev

    2017-02-01

    Full Text Available The Hom-1 vesivirus was reported in 1998 following the inadvertent transmission of the animal calicivirus San Miguel sea lion virus to a human host in a laboratory. We characterized the Hom-1 strain and investigated the mechanism by which human cells could be infected. An expression library of 3,559 human plasma membrane proteins was screened for reactivity with Hom-1 virus-like particles, and a single interacting protein, human junctional adhesion molecule 1 (hJAM1, was identified. Transient expression of hJAM1 conferred susceptibility to Hom-1 infection on nonpermissive Chinese hamster ovary (CHO cells. Virus infection was markedly inhibited when CHO cells stably expressing hJAM were pretreated with anti-hJAM1 monoclonal antibodies. Cell lines of human origin were tested for growth of Hom-1, and efficient replication was observed in HepG2, HuH7, and SK-CO15 cells. The three cell lines (of hepatic or intestinal origin were confirmed to express hJAM1 on their surface, and clustered regularly interspaced short palindromic repeats/Cas9-mediated knockout of the hJAM1 gene in each line abolished Hom-1 propagation. Taken together, our data indicate that entry of the Hom-1 vesivirus into these permissive human cell lines is mediated by the plasma membrane protein hJAM1 as a functional receptor.

  12. Frequent Nek1 overexpression in human gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Jun [School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China); Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Cai, Yu, E-mail: aihaozuqiu22@163.com [School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China); Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Liu, Pin [Med-X Research Institute, Shanghai Jiao Tong University, Shanghai (China); Zhao, Weiguo [Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

    2016-08-05

    Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients’ poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87-MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ-resistance. - Highlights: • Nek1 is upregulated in multiple human glioma tissues and cell lines. • Nek1 overexpression correlates with glioma grades and patients’ KPS score. • Nek1 overexpression correlates with patients’ poor overall survival. • siRNA knockdown of Nek1 inhibits glioma cell growth. • siRNA knockdown of Nek1 sensitizes human glioma cells to temozolomide.

  13. Frequent Nek1 overexpression in human gliomas

    International Nuclear Information System (INIS)

    Zhu, Jun; Cai, Yu; Liu, Pin; Zhao, Weiguo

    2016-01-01

    Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients’ poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87-MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ-resistance. - Highlights: • Nek1 is upregulated in multiple human glioma tissues and cell lines. • Nek1 overexpression correlates with glioma grades and patients’ KPS score. • Nek1 overexpression correlates with patients’ poor overall survival. • siRNA knockdown of Nek1 inhibits glioma cell growth. • siRNA knockdown of Nek1 sensitizes human glioma cells to temozolomide.

  14. Development of organophosphate hydrolase activity in a bacterial homolog of human cholinesterase

    Science.gov (United States)

    Legler, Patricia; Boisvert, Susanne; Compton, Jaimee; Millard, Charles

    2014-07-01

    We applied a combination of rational design and directed evolution (DE) to Bacillus subtilis p-nitrobenzyl esterase (pNBE) with the goal of enhancing organophosphorus acid anhydride hydrolase (OPAAH) activity. DE started with a designed variant, pNBE A107H, carrying a histidine homologous with human butyrylcholinesterase G117H to find complementary mutations that further enhance its OPAAH activity. Five sites were selected (G105, G106, A107, A190, and A400) within a 6.7 Å radius of the nucleophilic serine O?. All 95 variants were screened for esterase activity with a set of five substrates: pNP-acetate, pNP-butyrate, acetylthiocholine, butyrylthiocholine, or benzoylthiocholine. A microscale assay for OPAAH activity was developed for screening DE libraries. Reductions in esterase activity were generally concomitant with enhancements in OPAAH activity. One variant, A107K, showed an unexpected 7-fold increase in its kcat/Km for benzoylthiocholine, demonstrating that it is also possible to enhance the cholinesterase activity of pNBE. Moreover, DE resulted in at least three variants with modestly enhanced OPAAH activity compared to wild type pNBE. A107H/A190C showed a 50-fold increase in paraoxonase activity and underwent a slow time- and temperature-dependent change affecting the hydrolysis of OPAA and ester substrates. Structural analysis suggests that pNBE may represent a precursor leading to human cholinesterase and carboxylesterase 1 through extension of two vestigial specificity loops; a preliminary attempt to transfer the Ω-loop of BChE into pNBE is described. pNBE was tested as a surrogate scaffold for mammalian esterases. Unlike butyrylcholinesterase and pNBE, introducing a G143H mutation (equivalent to G117H) did not confer detectable OP hydrolase activity on human carboxylesterase 1. We discuss the importance of the oxyanion-hole residues for enhancing the OPAAH activity of selected serine hydrolases.

  15. Stability of human interferon-beta 1: oligomeric human interferon-beta 1 is inactive but is reactivated by monomerization.

    Science.gov (United States)

    Utsumi, J; Yamazaki, S; Kawaguchi, K; Kimura, S; Shimizu, H

    1989-10-05

    Human interferon-beta 1 is extremely stable is a low ionic strength solution of pH 2 such as 10 mM HCl at 37 degrees C. However, the presence of 0.15 M NaCl led to a remarkable loss of antiviral activity. The molecular-sieve high-performance liquid chromatography revealed that, whereas completely active human interferon-beta 1 eluted as a 25 kDa species (monomeric form), the inactivated preparation eluted primarily as a 90 kDa species (oligomeric form). The specific activity (units per mg protein) of the oligomeric form was approx. 10% of that of the monomeric form. This observation shows that oligomeric human interferon-beta 1 is apparently in an inactive form. When the oligomeric eluate was resolved by polyacrylamide gel containing sodium dodecyl sulphate (SDS), it appeared to be monomeric under non-reducing conditions. Monomerization of the oligomeric human interferon-beta 1 by treatment with 1% SDS, fully regenerated its antiviral activity. These results suggest that the inactivation of the human interferon-beta 1 preparation was caused by its oligomerization via hydrophobic interactions without the formation of intermolecular disulphide bonds. These oligomers can be dissociated by SDS to restore biological activity.

  16. Involvement of human endogenous retroviral syncytin-1 in human osteoclast fusion

    DEFF Research Database (Denmark)

    Søe, Kent; Andersen, Thomas Lykke; Hobolt-Pedersen, Anne-Sofie

    2011-01-01

    fusion of the lipid bilayers of their cell membranes are still unknown. Syncytin-1 is a protein encoded by a human endogenous retroviral gene which was stably integrated into the human ancestor genome more than 24 million years ago. Upon activation, syncytin-1 is able to destabilize the lipid bilayer....... This was documented through Q-PCR, Western blot and immunofluorescence analyses. These in vitro findings were confirmed by immunohistochemical stainings in human iliac crest biopsies. A syncytin-1 inhibitory peptide reduced the number of nuclei per osteoclast by 30%, as well as TRACP activity. From a mechanistic...

  17. YY1 positively regulates human UBIAD1 expression

    International Nuclear Information System (INIS)

    Funahashi, Nobuaki; Hirota, Yoshihisa; Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato; Suhara, Yoshitomo; Okano, Toshio

    2015-01-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K 1 ) and a series of bacterial menaquionones (MK-n; vitamin K 2 ). Menadione (vitamin K 3 ) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1 promoter

  18. YY1 positively regulates human UBIAD1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Funahashi, Nobuaki, E-mail: nfunahashi@ri.ncgm.go.jp [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Hirota, Yoshihisa [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka (Japan); Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Suhara, Yoshitomo [Department of Bioscience and Engineering, Shibaura Institute of Technology, Saitama (Japan); Okano, Toshio [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan)

    2015-05-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K{sub 1}) and a series of bacterial menaquionones (MK-n; vitamin K{sub 2}). Menadione (vitamin K{sub 3}) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1

  19. A follow-up study on brainstem atrophy in progressive supranuclear palsy. When does brain MRI contribute to the differential diagnosis between progressive supranuclear palsy and Parkinson disease?

    International Nuclear Information System (INIS)

    Yamamoto, Toshiyuki; Oya, Yasushi; Ogawa, Masafumi; Ogata, Katsuhisa; Kawai, Mitsuru

    2003-01-01

    The objective of this study was to investigate when the MRI can discriminate progressive supranuclear palsy (PSP) from Parkinson disease (PD). We obtained the following parameters using T1-weighted axial images of the midbrain and the middle pons from 40 studies of 17 PSP patients and 26 studies of 26 PD patients; anteroposterior diameter of the pons (Pons AP), anteroposterior length of the pontine tegmentum (Pons T), anteroposterior diameter of the midbrain (Midbrain AP), ratio of anteroposterior diameter of the pontine base to that of the pontine tegmentum (Pons B/T ratio), ratio of the sum of the bilateral crus cerebri widths to the midbrain AP (Midbrain [Cr+Cl]/AP ratio). All the PSP patients were studied more than twice and each study was classified into four groups according to the duration of the illness; less than 24 months (7 studies), from 24 to 47 months (10 studies), from 48 to 71 months (14 studies) and 72 months or longer (9 studies). The first MRI studies (duration of disease 39.9±22.1 months) were compared with the second studies (duration of disease 67.6±31.6 months) in 17 PSP patients. Pons AP, Pons T, and Midbrain AP were significantly smaller in the second studies, indicating progressive pontine and midbrain atrophy. Compared with the PD group, the PSP group showed significant atrophy four years after onset of the disease in Pons AP and two years in Pons T. Pons B/T ratio, and Midbrain [Cr+Cl]/AP ratio were significantly smaller in the PSP group two years after onset, suggesting midbrain and pontine tegmentum atrophy. The diagnostic MRI criteria of Pons B/T ratio more than four and Midbrain [Cr+Cl]/AP ratio more than two each showed accuracy in PSP of more than 70% two years after onset. Discrimination of PSP from PD was difficult during the first two years after onset. The atrophic process in the midbrain and the pontine tegmentum may precede that of the pontine base. Pons B/T ratio and Midbrain [Cr+Cl]/AP ratio presented here are potentially

  20. Lysophosphatidylcholine hydrolases of human erythrocytes, lymphocytes, and brain: Sensitive targets of conserved specificity for organophosphorus delayed neurotoxicants

    International Nuclear Information System (INIS)

    Vose, Sarah C.; Holland, Nina T.; Eskenazi, Brenda; Casida, John E.

    2007-01-01

    Brain neuropathy target esterase (NTE), associated with organophosphorus (OP)-induced delayed neuropathy, has the same OP inhibitor sensitivity and specificity profiles assayed in the classical way (paraoxon-resistant, mipafox-sensitive hydrolysis of phenyl valerate) or with lysophosphatidylcholine (LysoPC) as the substrate. Extending our earlier observation with mice, we now examine human erythrocyte, lymphocyte, and brain LysoPC hydrolases as possible sensitive targets for OP delayed neurotoxicants and insecticides. Inhibitor profiling of human erythrocytes and lymphocytes gave the surprising result of essentially the same pattern as with brain. Human erythrocyte LysoPC hydrolases are highly sensitive to OP delayed neurotoxicants, with in vitro IC 50 values of 0.13-85 nM for longer alkyl analogs, and poorly sensitive to the current OP insecticides. In agricultural workers, erythrocyte LysoPC hydrolyzing activities are similar for newborn children and their mothers and do not vary with paraoxonase status but have high intersample variation that limits their use as a biomarker. Mouse erythrocyte LysoPC hydrolase activity is also of low sensitivity in vitro and in vivo to the OP insecticides whereas the delayed neurotoxicant ethyl n-octylphosphonyl fluoride inhibits activity in vivo at 1-3 mg/kg. Overall, inhibition of blood LysoPC hydrolases is as good as inhibition of brain NTE as a predictor of OP inducers of delayed neuropathy. NTE and lysophospholipases (LysoPLAs) both hydrolyze LysoPC, yet they are in distinct enzyme families with no sequence homology and very different catalytic sites. The relative contributions of NTE and LysoPLAs to LysoPC hydrolysis and clearance from erythrocytes, lymphocytes, and brain remain to be defined

  1. mTORC1 directly phosphorylates and regulates human MAF1.

    Science.gov (United States)

    Michels, Annemieke A; Robitaille, Aaron M; Buczynski-Ruchonnet, Diane; Hodroj, Wassim; Reina, Jaime H; Hall, Michael N; Hernandez, Nouria

    2010-08-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1.

  2. Contribución al estudio y optimización de dispositivos basados en holografía dinámica para su uso en redes ópticas pasivas multiplexadas en longitud de onda Wdm-Pon

    OpenAIRE

    Martín Minguez, Alfredo

    2007-01-01

    La utilización de Redes Ópticas Pasivas Multiplexadas por División en el Tiempo (TDMPON), y más recientemente de las Redes Ópticas Pasivas Multiplexadas en Longitud de Onda (WDM-PON), con sus dos principales tecnologías, CWDM y DWDM, en distintas topologías de red para optimizar los recursos disponibles, implica el uso de diversos componentes ópticos como transmisores, receptores, de/multiplexores, filtros, etc. Es en este contexto donde el uso de dispositivos holográficos, WDM sintonizables,...

  3. Regulation of human skeletal stem cells differentiation by Dlk1/Pref-1

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Jensen, Charlotte H; Gutierrez, Gloria

    2004-01-01

    Dlk-1/Pref-1 was identified as a novel regulator of human skeletal stem cell differentiation. Dlk1/Pref-1 is expressed in bone and cultured osteoblasts, and its constitutive overexpression led to inhibition of osteoblast and adipocyte differentiation of human marrow stromal cells. INTRODUCTION......: Molecular control of human mesenchymal stem cell (hMSC) differentiation into osteoblasts and adipocytes is not known. In this study, we examined the role of delta-like 1/preadipocyte factor-1 (Dlk1/Pref-1) in regulating the differentiation of hMSCs. MATERIALS AND METHODS: As a model for hMSCs, we have...... was used to confirm the in vitro effect of Dlk/Pref-1 on bone formation. RESULTS: Dlk1/Pref-1 was found to be expressed in fetal and adult bone, hMSCs, and some osteoblastic cell lines. A retroviral vector containing the human Dlk1/Pref-1 cDNA was used to create a cell line (hMSC-dlk1) expressing high...

  4. Convergência em redes de acesso de nova geração

    OpenAIRE

    Dias, Pedro Miguel

    2015-01-01

    Due to the continuous growth of bandwidth need, passive optical networks (PONs) emerged. From the Gigabit-PON (G-PON), 10 Gigabit-PON (XG-PON) and Time Wavelength Division Multiplexing PON (TWDM-PON), they still being made studies on passive optical networks that can meet the bandwidth requirements of the future, such as the Ultra Dense Wavelength Division Multiplexing PON (UDWDM-PON). In this thesis, the mentioned technologies are studied, describing the main features of the existing ones...

  5. Identification of Human H1N2 and Human-Swine Reassortant H1N2 and H1N1 Influenza A Viruses among Pigs in Ontario, Canada (2003 to 2005)†

    OpenAIRE

    Karasin, Alexander I.; Carman, Suzanne; Olsen, Christopher W.

    2006-01-01

    Since 2003, three novel genotypes of H1 influenza viruses have been recovered from Canadian pigs, including a wholly human H1N2 virus and human-swine reassortants. These isolates demonstrate that human-lineage H1N2 viruses are infectious for pigs and that viruses with a human PB1/swine PA/swine PB2 polymerase complex can replicate in pigs.

  6. Signal intensity change on unenhanced T1-weighted images in dentate nucleus and globus pallidus after multiple administrations of gadoxetate disodium: an intraindividual comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Conte, Giorgio; Minotti, Marta; De Piano, Francesca [Universita degli Studi di Milano, Postgraduation School in Radiodiagnostics, Milan (Italy); Preda, Lorenzo [Universita degli Studi di Pavia, Department of Clinical-Surgical Diagnostic and Pediatric Sciences, Pavia (Italy); National Center of Oncological Hadrontherapy (CNAO Foundation), Division of Radiology, Pavia (Italy); Cocorocchio, Emilia; Ferrucci, Pier Francesco [European Institute of Oncology, Melanoma and Sarcoma Medical Oncology Division, Milan (Italy); Raimondi, Sara [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Giannitto, Caterina; Petralia, Giuseppe [European Institute of Oncology, Division of Radiology, Milan (Italy); Bellomi, Massimo [European Institute of Oncology, Division of Radiology, Milan (Italy); Universita degli Studi di Milano, Oncology and Haematology/Oncology Department, Milan (Italy)

    2017-10-15

    To investigate whether there is an increased signal intensity (SI) of dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance imaging (MRI), in patients who had undergone multiple administrations of gadoxetate disodium. We retrospectively included stage III melanoma patients, who had been previously enrolled in a trial of adjuvant therapy and who had undergone whole-body contrast-enhanced MRIs with gadoxetate disodium every three months for their follow-up. The SI ratios of DN-to-pons and GP-to-thalamus on unenhanced T1-weighted images were calculated. The difference in SI ratios between the first and the last MRI examinations was assessed and a linear mixed model was performed to detect how SI ratios varied with the number of administrations. Eighteen patients were included in our study. The number of gadoxetate disodium administrations ranged from 2 to 18. Paired t-test did not show any significant difference in DN-to-pons (p=0.21) and GP-to-thalamus (p=0.09) SI ratios by the end of the study. DN-to-pons SI ratio and GP-to-thalamus SI ratio did not significantly increase with increasing the number of administrations (p=0.14 and p=0.06, respectively). Multiple administrations of gadoxetate disodium are not associated with increased SI in DN and GP in the brain. (orig.)

  7. Signal to Noise Ratio (SNR Enhancement Comparison of Impulse-, Coding- and Novel Linear-Frequency-Chirp-Based Optical Time Domain Reflectometry (OTDR for Passive Optical Network (PON Monitoring Based on Unique Combinations of Wavelength Selective Mirrors

    Directory of Open Access Journals (Sweden)

    Christopher M. Bentz

    2014-03-01

    Full Text Available We compare optical time domain reflectometry (OTDR techniques based on conventional single impulse, coding and linear frequency chirps concerning their signal to noise ratio (SNR enhancements by measurements in a passive optical network (PON with a maximum one-way attenuation of 36.6 dB. A total of six subscribers, each represented by a unique mirror pair with narrow reflection bandwidths, are installed within a distance of 14 m. The spatial resolution of the OTDR set-up is 3.0 m.

  8. Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.

    Science.gov (United States)

    Church, Rachel J; Kullak-Ublick, Gerd A; Aubrecht, Jiri; Bonkovsky, Herbert L; Chalasani, Naga; Fontana, Robert J; Goepfert, Jens C; Hackman, Frances; King, Nicholas M P; Kirby, Simon; Kirby, Patrick; Marcinak, John; Ormarsdottir, Sif; Schomaker, Shelli J; Schuppe-Koistinen, Ina; Wolenski, Francis; Arber, Nadir; Merz, Michael; Sauer, John-Michael; Andrade, Raul J; van Bömmel, Florian; Poynard, Thierry; Watkins, Paul B

    2018-01-22

    Current blood biomarkers are suboptimal in detecting drug-induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of fourteen promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n=192 and =81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n=55 and =92) and DILI patients (n=98, =28, and =143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH), total keratin 18 (K18), caspase cleaved K18 (ccK18), glutathione S-transferase alpha (GSTα), alpha fetoprotein (AFP), arginase-1 (ARG1), osteopontin (OPN), sorbitol dehydrogenase (SDH), fatty acid binding protein (FABP1), cadherin-5 (CDH5), macrophage colony stimulating factor receptor (MCSFR), paraoxonase 1 (PON1, normalized to prothrombin protein), and leucocyte cell-derived chemotaxin-2 (LECT2). Most candidate biomarkers were significantly altered in DILI cases compared to healthy volunteers. GLDH correlated more closely with gold standard alanine aminotransferase (ALT) than miR-122 and there was a surprisingly wide inter- and intra-individual variability of miR-122 levels among the healthy volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with liver-related death or transplant within 6 months of DILI-onset. Prediction of prognosis among DILI patients using Model for End-stage Liver Disease (MELD) was improved by incorporation of K18 and MCSFR levels. GLDH appears to be more useful than miR-122 in identifying DILI patients. K18, OPN and MCSFR are promising candidates for prediction of prognosis during an acute DILI event. Serial assessment of these biomarkers in large prospective studies will help further delineate their role in DILI diagnosis and management. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  9. Antibodies Against β2-Glycoprotein I Complexed With an Oxidised Lipoprotein Relate to Intima Thickening of Carotid Arteries in Primary Antiphospholipid Syndrome

    Directory of Open Access Journals (Sweden)

    P. R. J. Ames

    2006-01-01

    Full Text Available To explore whether antibodies against β2-glycoprotein I (β2GPI complexed to 7-ketocholesteryl-9-carboxynonanoate (oxLig-1 and to oxidised low-density lipoproteins (oxLDL relate to paraoxonase activity (PONa and/or intima media thickness (IMT of carotid arteries in primary antiphospholipid syndrome (PAPS. As many as 29 thrombotic patients with PAPS, 10 subjects with idiopathic antiphospholipid antibodies (aPL without thrombosis, 17 thrombotic patients with inherited thrombophilia and 23 healthy controls were investigated. The following were measured in all participants: β2GPI−oxLDL complexes, IgG anti-β2GPI−oxLig-1, IgG anti-β2GPI−oxLDL antibodies (ELISA, PONa, (para-nitrophenol method, IMT of common carotid (CC artery, carotid bifurcation (B, internal carotid (IC by high resolution sonography. β2GPI−oxLDL complex was highest in the control group (p < 0.01, whereas, IgG anti-β2GPI−oxLig1 and IgG anti-β2GPI−oxLDL were highest in PAPS (p < 0.0001. In healthy controls, β2GPI−oxLDL complexes positively correlated to IMT of the IC (p = 0.007 and negatively to PONa after correction for age (p < 0.03. PONa inversely correlated with age (p = 0.008. In PAPS, IgG anti-2GPI−oxLig-1 independently predicted PONa (p = 0.02 and IMT of B (p = 0.003, CC, (p = 0.03 and of IC (p = 0.04. In PAPS, PONa inversely correlated to the IMT of B, CC and IC (p = 0.01, 0.02 and 0.003, respectively. IgG anti-2GPI−oxLig-1 may be involved in PAPS related atherogenesis via decreased PON activity.

  10. MRI comparative study of the progressive supranuclear palsy, striatonigral degeneration and Parkinson disease

    International Nuclear Information System (INIS)

    Wu Wulin; Lou Mingwu; Wang Xiaoyi; Liao Weihua

    2009-01-01

    Objective: To provide a reliable differential diagnosis among the progressive supranuclear palsy (PSP), striatonigral degeneration (SND) and Parkinson disease (PD). Methods: Conventional MRI data in clinically proved PSP (8 cases), SND (9 cases), PD (12 cases) and 12 normal controls were retrospectively analyzed. Midbrain area, pons area, pons diameter and middle cerebellar peduncles width were measured. The ratio of pons area over midbrain area (pons area / midbrain area) was calculated in all patients and normal controls. Then one way ANOVA and a Kruskal-Wallis H test were used for statistical analysis. Results: Midbrain area of the PSP group [(85.8 ± 12.0 mm 2 ] was the smallest, and there was statistically significant difference (P 2 ], PD group [(133.5 ± 10.8)mm 2 ] and the control group [(135.9 ± 7.5) mm 2 ]. There was no overlapping in the distribution of midbrain area between the PSP group (66.0-98.2 mm 2 ) and SND, PD and normal groups (116.2-142.1, 110.8-146.2 and 121.7-145.8 mm 2 ). The pons area-midbrain area ratio (P/M) of the PSP group (5.9 ± 0.8) was the largest in four groups, and there was statistically significant difference (P 2 , (18.6 ± 2.0) mm and (12.9 ± 2.4) mm] in all groups, and significant difference (P 2 , (22.7 ± 1.7) mm and (16.3 ± 1.1) mm], PD group [3.8 ± 0.3, (500.2 ± 25.8) mm 2 , (23.7 ± 1.0) mm and (16.8 ± 1.1) mm] and the control group [3.8 ± 0.3, (508.8 ± 20.6) mm 2 , (23.2 ± 1.2) mm and (16.4 ± 0.9) mm]. But the PD group and control group had no statistically significant difference in the midbrain area, pons area, pons diameter, P/M and middle cerebellar peduncles width (P > 0.05). Conclusion: MRI measurements helps in the differential diagnosis among PSP, SND and PD. (authors)

  11. mTORC1 Directly Phosphorylates and Regulates Human MAF1

    Science.gov (United States)

    Michels, Annemieke A.; Robitaille, Aaron M.; Buczynski-Ruchonnet, Diane; Hodroj, Wassim; Reina, Jaime H.; Hall, Michael N.; Hernandez, Nouria

    2010-01-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1. PMID:20516213

  12. Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

    Science.gov (United States)

    Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

    1989-03-15

    Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

  13. Magnetic Resonance and Spectroscopy of the Human Brain in Gulf War Illness

    National Research Council Canada - National Science Library

    Weiner, Michael W

    2005-01-01

    The goal of this project is to test the hypotheses that: Subjects with GWI have reduced NAA in the basal ganglia and pons, which are not accounted for by confounds such as PTSD, depression, and alcohol abuse...

  14. Human hepatocyte depletion in the presence of HIV-1 infection in dual reconstituted humanized mice

    Science.gov (United States)

    Wang, Weimin; Cheng, Yan; Makarov, Edward; Ganesan, Murali; Gebhart, Catherine L.; Gorantla, Santhi; Osna, Natalia

    2018-01-01

    ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection impairs liver function, and liver diseases have become a leading cause of morbidity in infected patients. The immunopathology of liver damage caused by HIV-1 remains unclear. We used chimeric mice dually reconstituted with a human immune system and hepatocytes to address the relevance of the model to pathobiology questions related to human hepatocyte survival in the presence of systemic infection. TK-NOG males were transplanted with mismatched human hematopoietic stem/progenitor cells and hepatocytes, human albumin concentration and the presence of human immune cells in blood were monitored for hepatocytes and immune reconstitution, and mice were infected with HIV-1. HIV-1-infected animals showed a decline in human albumin concentration with a significant reduction in percentage of human hepatocytes compared to uninfected mice. The decrease in human albumin levels correlated with a decline in CD4+ cells in the liver and with an increase in HIV-1 viral load. HIV-1 infection elicited proinflammatory response in the immunological milieu of the liver in HIV-infected mice compared to uninfected animals, as determined by upregulation of IL23, CXCL10 and multiple toll-like receptor expression. The inflammatory reaction associated with HIV-1 infection in vivo could contribute to the depletion and dysfunction of hepatocytes. The dual reconstituted TK-NOG mouse model is a feasible platform to investigate hepatocyte-related HIV-1 immunopathogenesis. This article has an associated First Person interview with the first author of the paper. PMID:29361613

  15. Human hepatocyte depletion in the presence of HIV-1 infection in dual reconstituted humanized mice

    Directory of Open Access Journals (Sweden)

    Raghubendra Singh Dagur

    2018-02-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection impairs liver function, and liver diseases have become a leading cause of morbidity in infected patients. The immunopathology of liver damage caused by HIV-1 remains unclear. We used chimeric mice dually reconstituted with a human immune system and hepatocytes to address the relevance of the model to pathobiology questions related to human hepatocyte survival in the presence of systemic infection. TK-NOG males were transplanted with mismatched human hematopoietic stem/progenitor cells and hepatocytes, human albumin concentration and the presence of human immune cells in blood were monitored for hepatocytes and immune reconstitution, and mice were infected with HIV-1. HIV-1-infected animals showed a decline in human albumin concentration with a significant reduction in percentage of human hepatocytes compared to uninfected mice. The decrease in human albumin levels correlated with a decline in CD4+ cells in the liver and with an increase in HIV-1 viral load. HIV-1 infection elicited proinflammatory response in the immunological milieu of the liver in HIV-infected mice compared to uninfected animals, as determined by upregulation of IL23, CXCL10 and multiple toll-like receptor expression. The inflammatory reaction associated with HIV-1 infection in vivo could contribute to the depletion and dysfunction of hepatocytes. The dual reconstituted TK-NOG mouse model is a feasible platform to investigate hepatocyte-related HIV-1 immunopathogenesis. This article has an associated First Person interview with the first author of the paper.

  16. Cloning of a cDNA encoding the rat high molecular weight neurofilament peptide (NF-H): Developmental and tissue expression in the rat, and mapping of its human homologue to chromosomes 1 and 22

    International Nuclear Information System (INIS)

    Lieberburg, I.; Spinner, N.; Snyder, S.

    1989-01-01

    Neurofilaments (NFs) are the intermediate filaments specific to nervous tissue. Three peptides with apparent molecular masses of approximately 68 (NF-L), 145 (NF-M), and 200 (NF-H) kDa appear to be the major components of NF. The expression of these peptides is specific to nervous tissue and is developmentally regulated. Recently, complete cDNAs encoding NF-L and NF-M, and partial cDNAs encoding NF-H, have been described. To better understand the normal pathophysiology of NFs the authors chose to clone the cDNA encoding the rat NF-H peptide. Using monoclonal antibodies that recognized NF-H, they screened a rat brain λgt11 library and identified a clone that contained a 2,100-nucleotide cDNA insert representing the carboxyl-terminal portion of the NF-H protein. Levels of NF-H mRNA varied 20-fold among brain regions, with highest levels in pons/medulla, spinal cord, and cerebellum, and lowest levels in olfactory bulb and hypothalamus. Based on these results, the authors infer that half of the developmental increase and most of the interregional variation in the levels of the NF-H mRNA are mediated through message stabilization. Sequence information revealed that the carboxyl-terminal region of the NF-H peptide contained a unique serine-, proline-, alanine-, glutamic acid-, and lysine-rich repeat. Genomic blots revealed a single copy of the gene in the rat genome and two copies in the human genome. In situ hybridizations performed on human chromosomes mapped the NF-H gene to chromosomes 1 and 22

  17. The PDL1-PD1 Axis Converts Human Th1 Cells Into Regulatory T Cells

    Science.gov (United States)

    Amarnath, Shoba; Mangus, Courtney W.; Wang, James C.M.; Wei, Fang; He, Alice; Kapoor, Veena; Foley, Jason E.; Massey, Paul R.; Felizardo, Tania C.; Riley, James L.; Levine, Bruce L.; June, Carl H.; Medin, Jeffrey A.; Fowler, Daniel H.

    2011-01-01

    Immune surveillance by T helper type 1 (Th1) cells is critical for the host response to tumors and infection, but also contributes to autoimmunity and graft-versus-host disease (GvHD) after transplantation. The inhibitory molecule programmed death ligand-1 (PDL1) has been shown to anergize human Th1 cells, but other mechanisms of PDL1-mediated Th1 inhibition such as the conversion of Th1 cells to a regulatory phenotype have not been well characterized. We hypothesized that PDL1 may cause Th1 cells to manifest differentiation plasticity. Conventional T cells or irradiated K562 myeloid tumor cells overexpressing PDL1 converted TBET+ Th1 cells into FOXP3+ regulatory T cells (TREGS) in vivo, thereby preventing human-into-mouse xenogeneic GvHD (xGvHD). Either blocking PD1 expression on Th1 cells by siRNA targeting or abrogation of PD1 signaling by SHP1/2 pharmacologic inhibition stabilized Th1 cell differentiation during PDL1 challenge and restored the capacity of Th1 cells to mediate lethal xGVHD. PD1 signaling therefore induces human Th1 cells to manifest in vivo plasticity, resulting in a TREG phenotype that severely impairs cell-mediated immunity. Converting human Th1 cells to a regulatory phenotype with PD1 signaling provides a potential way to block GvHD after transplantation. Moreover, because this conversion can be prevented by blocking PD1 expression or pharmacologically inhibiting SHP1/2, this pathway provides a new therapeutic direction for enhancing T cell immunity to cancer and infection. PMID:22133721

  18. Airborne particulate matter PM2.5 from Mexico City affects the generation of reactive oxygen species by blood neutrophils from asthmatics: an in vitro approach

    Directory of Open Access Journals (Sweden)

    Ceballos Guillermo

    2009-06-01

    Full Text Available Abstract Background The Mexico City Metropolitan Area is densely populated, and toxic air pollutants are generated and concentrated at a higher rate because of its geographic characteristics. It is well known that exposure to particulate matter, especially to fine and ultra-fine particles, enhances the risk of cardio-respiratory diseases, especially in populations susceptible to oxidative stress. The aim of this study was to evaluate the effect of fine particles on the respiratory burst of circulating neutrophils from asthmatic patients living in Mexico City. Methods In total, 6 subjects diagnosed with mild asthma and 11 healthy volunteers were asked to participate. Neutrophils were isolated from peripheral venous blood and incubated with fine particles, and the generation of reactive oxygen species was recorded by chemiluminescence. We also measured plasma lipoperoxidation susceptibility and plasma myeloperoxidase and paraoxonase activities by spectrophotometry. Results Asthmatic patients showed significantly lower plasma paraoxonase activity, higher susceptibility to plasma lipoperoxidation and an increase in myeloperoxidase activity that differed significantly from the control group. In the presence of fine particles, neutrophils from asthmatic patients showed an increased tendency to generate reactive oxygen species after stimulation with fine particles (PM2.5. Conclusion These findings suggest that asthmatic patients have higher oxidation of plasmatic lipids due to reduced antioxidant defense. Furthermore, fine particles tended to increase the respiratory burst of blood human neutrophils from the asthmatic group. On the whole, increased myeloperoxidase activity and susceptibility to lipoperoxidation with a concomitant decrease in paraoxonase activity in asthmatic patients could favor lung infection and hence disrupt the control of asthmatic crises.

  19. Intravenous injection of gadobutrol in an epidemiological study group did not lead to a difference in relative signal intensities of certain brain structures after 5 years

    Energy Technology Data Exchange (ETDEWEB)

    Kromrey, Marie-Luise; Liedtke, Kim Rouven; Langner, Soenke; Kirsch, Michael; Kuehn, Jens-Peter [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Ittermann, Till [University Medicine Greifswald, Institute for Community Medicine, Greifswald (Germany); Weitschies, Werner [University Greifswald, Institute of Biopharmacy and Pharmaceutical Technology, Greifswald (Germany)

    2017-02-15

    To investigate if application of macrocyclic gadolinium-based contrast agents in volunteers is associated with neuronal deposition detected by magnetic resonance imaging in a 5-year longitudinal survey. Three hundred eighty-seven volunteers who participated in a population-based study were enrolled. Subjects underwent plain T1-weighted brain MRI at baseline and 5 years later with identical sequence parameters. At baseline, 271 participants additionally received intravenous injection of the macrocyclic contrast agent gadobutrol (1.5 mmol/kg). A control group including 116 subjects received no contrast agent. Relative signal intensities of thalamus, pallidum, pons and dentate nucleus were compared at baseline and follow-up. No difference in relative signal intensities was observed between contrast group (thalamus, p = 0.865; pallidum, p = 0.263; pons, p = 0.533; dentate nucleus, p = 0.396) and control group (thalamus, p = 0.683; pallidum; p = 0.970; pons, p = 0.773; dentate nucleus, p = 0.232) at both times. Comparison between both groups revealed no significant differences in relative signal intensities (thalamus, p = 0.413; pallidum, p = 0.653; pons, p = 0.460; dentate nucleus, p = 0.751). The study showed no significant change in globus pallidus-to-thalamus or dentate nucleus-to-pons ratios. Five years after administration of a 1.5-fold dose gadobutrol to normal subjects, signal intensity of thalamus, pallidum, pons and dentate nucleus did not differ from participants who had not received gadobutrol. (orig.)

  20. Cloning the interleukin 1 receptor from human T cells

    International Nuclear Information System (INIS)

    Sims, J.E.; Acres, R.B.; Grubin, C.E.; McMahan, C.J.; Wignall, J.M.; March, C.J.; Dower, S.K.

    1989-01-01

    cDNA clones of the interleukin 1 (IL-1) receptor expressed in a human T-cell clone have been isolated by using a murine IL-1 receptor cDNA as a probe. The human and mouse receptors show a high degree of sequence conservation. Both are integral membrane proteins possessing a single membrane-spanning segment. Similar to the mouse receptor, the human IL-1 receptor contains a large cytoplasmic region and an extracellular, IL-1 binding portion composed of three immunoglobulin-like domains. When transfected into COS cells, the human IL-1 receptor cDNA clone leads to expression of two different affinity classes of receptors, with K a values indistinguishable from those determined for IL-1 receptors in the original T-cell clone. An IL-1 receptor expressed in human dermal fibroblasts has also been cloned and sequenced and found to be identical to the IL-1 receptor expressed in T cells

  1. Further studies on the lithium phosphorus oxynitride solid electrolyte

    International Nuclear Information System (INIS)

    Pichonat, Tristan; Lethien, Christophe; Tiercelin, Nicolas; Godey, Sylvie; Pichonat, Emmanuelle; Roussel, Pascal; Colmont, Marie; Rolland, Paul Alain

    2010-01-01

    First step in the way to the fabrication of an all-solid microbattery for autonomous wireless sensor node, amorphous thin solid films of lithium phosphorus oxynitride (LiPON) were prepared by radio-frequency sputtering of a mixture target of P 2 O 5 /Li 2 O in ambient nitrogen atmosphere. The morphology, composition, and ionic conductivity were characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and A.C. impedance spectroscopy. With a thickness of 1.4 μm, the obtained LiPON amorphous layer provided an ionic conductivity close to 6 x 10 -7 S cm -1 at room temperature. MicroRaman UV spectroscopy study was successfully carried out for the first time on LiPON thin films to complete the characterization and bring further information on LiPON structure.

  2. Assessment of human exposure to fumonisin B1

    NARCIS (Netherlands)

    Nijs, M. de; Egmond, H.P. van; Nauta, M.; Rombouts, F.M.; Notermans, S.H.W.

    1998-01-01

    Fumonisin B1 is currently regarded as the most significant mycotoxin produced by Fusarium spp. It has carcinogenic properties and may play a role in the etiology of human esophageal cancer. The human population is exposed to fumonisin B1 primarily by intake of fumonisin B1-contaminated maize. Maize

  3. Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

    International Nuclear Information System (INIS)

    Waser, Beatrice; Reubi, Jean Claude

    2014-01-01

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the 125 iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer 125 I-GLP-1(7-36)amide. Receptor autoradiography studies with 125 I-GLP-1(7-36)amide agonist or 125 I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist 125 I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer 125 I-GLP-1(7-36)amide. For comparison, 125 I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with 125 I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

  4. Effects of Urtica dioica on hepatic ischemia‐reperfusion injury in rats

    Science.gov (United States)

    Kandis, Hayati; Karapolat, Sami; Yildirim, Umran; Saritas, Ayhan; Gezer, Suat; Memisogullari, Ramazan

    2010-01-01

    OBJECTIVES: To evaluate the effects of Urtica dioica on hepatic ischemia‐reperfusion injury. METHODS: Thirty adult male Wistar albino rats were divided into three groups: sham group (group 1), control group (group 2), and Urtica dioica group (group 3). All the rats were exposed to hepatic ischemia for 60 min, followed by 60 min of reperfusion. In group 2, a total of 2 ml/kg 0.9% saline solution was given intraperitoneally. In group 3, a total of 2 ml/kg Urtica dioica was given intraperitoneally. At the end of the procedure, liver tissue and blood samples were taken from all rats. Serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ceruloplasmin, catalase, paraoxonase, arylesterase, and lipid hydroperoxide levels were measured. Liver tissue histopathologies were also evaluated by light microscopy. RESULTS: Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels were significantly higher in group 2 than in group 1, and significantly lower in group 3 than in group 2. Also, group 2 had higher serum lipid hydroperoxides and ceruloplasmin levels but lower catalase, paraoxonase, and arylesterase levels than group 1. In group 3, serum lipid hydroperoxides and ceruloplasmin levels were significantly lower, and catalase, paraoxonase, and arylesterase levels were higher than those in group 2. Histopathological examination showed that liver tissue damage was significantly decreased in group 3 compared with group 2. CONCLUSIONS: Urtica dioica has a protective effect on the liver in hepatic ischemia‐reperfusion‐injured rats. PMID:21340227

  5. Effects of Urtica dioica on hepatic ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Kandis, Hayati; Karapolat, Sami; Yildirim, Umran; Saritas, Ayhan; Gezer, Suat; Memisogullari, Ramazan

    2010-01-01

    To evaluate the effects of Urtica dioica on hepatic ischemia-reperfusion injury. Thirty adult male Wistar albino rats were divided into three groups: sham group (group 1), control group (group 2), and Urtica dioica group (group 3). All the rats were exposed to hepatic ischemia for 60 min, followed by 60 min of reperfusion. In group 2, a total of 2 ml/kg 0.9% saline solution was given intraperitoneally. In group 3, a total of 2 ml/kg Urtica dioica was given intraperitoneally. At the end of the procedure, liver tissue and blood samples were taken from all rats. Serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ceruloplasmin, catalase, paraoxonase, arylesterase, and lipid hydroperoxide levels were measured. Liver tissue histopathologies were also evaluated by light microscopy. Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels were significantly higher in group 2 than in group 1, and significantly lower in group 3 than in group 2. Also, group 2 had higher serum lipid hydroperoxides and ceruloplasmin levels but lower catalase, paraoxonase, and arylesterase levels than group 1. In group 3, serum lipid hydroperoxides and ceruloplasmin levels were significantly lower, and catalase, paraoxonase, and arylesterase levels were higher than those in group 2. Histopathological examination showed that liver tissue damage was significantly decreased in group 3 compared with group 2. Urtica dioica has a protective effect on the liver in hepatic ischemia-reperfusion-injured rats.

  6. Variation pattern of particulate organic carbon and nitrogen in oceans and inland waters

    Science.gov (United States)

    Huang, Changchun; Jiang, Quanliang; Yao, Ling; Yang, Hao; Lin, Chen; Huang, Tao; Zhu, A.-Xing; Zhang, Yimin

    2018-03-01

    We examined the relationship between, and variations in, particulate organic carbon (POC) and particulate organic nitrogen (PON) based on previously acquired ocean and inland water data. The latitudinal dependency of POC / PON is significant between 20 and 90° N but weak in low-latitude areas and in the Southern Hemisphere. The mean values of POC / PON in the Southern Hemisphere and Northern Hemisphere were 7.40 ± 3.83 and 7.80 ± 3.92, respectively. High values of POC / PON appeared between 80-90 (12.2 ± 7.5) and 70-80° N (9.4 ± 6.4), while relatively low POC / PON was found from 20 (6.6 ± 2.8) to 40° N (6.7 ± 2.7). The latitudinal variation of POC / PON in the Northern Hemisphere is much stronger than in the Southern Hemisphere due to the influence of more terrestrial organic matter. Higher POC and PON could be expected in coastal waters. POC / PON growth ranged from 6.89 ± 2.38 to 7.59 ± 4.22 in the Northern Hemisphere, with an increasing rate of 0.0024 km from the coastal to open ocean. Variations of POC / PON in lake water also showed a similar latitude-variation tendency of POC / PON with ocean water but were significantly regulated by the lakes' morphology, trophic state and climate. Small lakes and high-latitude lakes prefer relatively high POC / PON, and large lakes and low-latitude lakes tend to prefer low POC / PON. The coupling relationship between POC and PON in oceans is much stronger than in inland waters. Variations in POC, PON and POC / PON in inland waters should receive more attention due to the implications of these values for the global carbon and nitrogen cycles and the indeterminacy of the relationship between POC and PON.

  7. CD1 and mycobacterial lipids activate human T cells.

    Science.gov (United States)

    Van Rhijn, Ildiko; Moody, D Branch

    2015-03-01

    For decades, proteins were thought to be the sole or at least the dominant source of antigens for T cells. Studies in the 1990s demonstrated that CD1 proteins and mycobacterial lipids form specific targets of human αβ T cells. The molecular basis by which T-cell receptors (TCRs) recognize CD1-lipid complexes is now well understood. Many types of mycobacterial lipids function as antigens in the CD1 system, and new studies done with CD1 tetramers identify T-cell populations in the blood of tuberculosis patients. In human populations, a fundamental difference between the CD1 and major histocompatibility complex systems is that all humans express nearly identical CD1 proteins. Correspondingly, human CD1 responsive T cells show evidence of conserved TCRs. In addition to natural killer T cells and mucosal-associated invariant T (MAIT cells), conserved TCRs define other subsets of human T cells, including germline-encoded mycolyl-reactive (GEM) T cells. The simple immunogenetics of the CD1 system and new investigative tools to measure T-cell responses in humans now creates a situation in which known lipid antigens can be developed as immunodiagnostic and immunotherapeutic reagents for tuberculosis disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Plane of nutrition during the preweaned period influences the pathophysiological responses to a combined intranasal bovine herpesvirus-1 and intratracheal Mannheimia haemolytica challenge in post-weaned Holstein calves

    Science.gov (United States)

    The objective was to determine whether previous plane of milk replacer nutrition (PON) influences the pathophysiological responses to a combined viral-bacterial respiratory challenge. Thirty Holstein calves (1 day of age) were assigned to treatments in a 2 x 3 factorial arrangement with preweaned PO...

  9. Atividade sérica de Paraoxanase durante o periparto de vacas leiteiras com diferentes concentrações de Lactogênio Placentário

    Directory of Open Access Journals (Sweden)

    Marina Menoncin Weschenfelder Rohenkohl

    2017-10-01

    Full Text Available A ação do hormônio Lactogênio Placentário Bovino (bLP no metabolismo materno ainda é pouco conhecida. Alguns marcadores, como a proteína de fase aguda Paraoxanase (PON1, são utilizados como indicadores da função hepática auxiliando na determinação da condição metabólica no período de transição em vacas leiteiras. O objetivo deste trabalho foi avaliar a atividade sérica de PON1 durante o periparto em vacas leiteiras com diferentes níveis de bLP. As vacas foram divididas em três grupos de acordo com as concentrações plasmáticas de bLP, em que BAIXO 2,68 ng mL-1 e 2,80 ng mL-1 (n=6. O período experimental ocorreu entre os 21 dias pré-parto e 28 dias pós-parto. Amostras de soro foram coletadas para a determinação das concentrações de bLP e atividade sérica de PON1. Houve diferença entre os três grupos (P ? 0,0001 de acordo com as concentrações de bLP, assim como entre os dias coletados (P ? 0,0001. No pré-parto, os níveis de PON1 apresentaram diferença entre grupos (P ? 0,05 e coletas (P ? 0,05. Vacas com alta concentração de bLP apresentaram menor atividade sérica de PON1 (P ? 0,05, enquanto vacas com baixos níveis do hormônio obtiveram maior atividade da enzima (P ? 0,05. No pós-parto não houve diferença entre grupos (P ? 0,10, houve diferença entre os dias coletados (P ? 0,0001 e interação entre grupos e coletas (P ? 0,01. O grupo com altas concentrações de bLP apresentou menores níveis de PON1 (P ? 0,01, enquanto vacas do grupo com baixo bLP mantiveram maiores concentrações de PON1 (P ? 0,01. Conclui-se que, vacas com maiores concentrações de bLP no período pré-parto apresentam redução na atividade sérica da enzima PON1 durante o período periparto.

  10. Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

    Energy Technology Data Exchange (ETDEWEB)

    Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland)

    2014-06-15

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the {sup 125}iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer {sup 125}I-GLP-1(7-36)amide. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist {sup 125}I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer {sup 125}I-GLP-1(7-36)amide. For comparison, {sup 125}I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with {sup 125}I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

  11. In Vitro Drug Metabolism by Human Carboxylesterase 1

    DEFF Research Database (Denmark)

    Thomsen, Ragnar; Rasmussen, Henrik B; Linnet, Kristian

    2014-01-01

    Carboxylesterase 1 (CES1) is the major hydrolase in human liver. The enzyme is involved in the metabolism of several important therapeutic agents, drugs of abuse, and endogenous compounds. However, no studies have described the role of human CES1 in the activation of two commonly prescribed...... a panel of therapeutic drugs and drugs of abuse to assess their inhibition of the hydrolysis of p-nitrophenyl acetate by recombinant CES1 and human liver microsomes. The screening assay confirmed several known inhibitors of CES1 and identified two previously unreported inhibitors: the dihydropyridine...... calcium antagonist, isradipine, and the immunosuppressive agent, tacrolimus. CES1 plays a role in the metabolism of several drugs used in the treatment of common conditions, including hypertension, congestive heart failure, and diabetes mellitus; thus, there is a potential for clinically relevant drug-drug...

  12. Caveolin-1 influences human influenza A virus (H1N1 multiplication in cell culture

    Directory of Open Access Journals (Sweden)

    Hemgård Gun-Viol

    2010-05-01

    Full Text Available Abstract Background The threat of recurring influenza pandemics caused by new viral strains and the occurrence of escape mutants necessitate the search for potent therapeutic targets. The dependence of viruses on cellular factors provides a weak-spot in the viral multiplication strategy and a means to interfere with viral multiplication. Results Using a motif-based search strategy for antiviral targets we identified caveolin-1 (Cav-1 as a putative cellular interaction partner of human influenza A viruses, including the pandemic influenza A virus (H1N1 strains of swine origin circulating from spring 2009 on. The influence of Cav-1 on human influenza A/PR/8/34 (H1N1 virus replication was determined in inhibition and competition experiments. RNAi-mediated Cav-1 knock-down as well as transfection of a dominant-negative Cav-1 mutant results in a decrease in virus titre in infected Madin-Darby canine kidney cells (MDCK, a cell line commonly used in basic influenza research as well as in virus vaccine production. To understand the molecular basis of the phenomenon we focussed on the putative caveolin-1 binding domain (CBD located in the lumenal, juxtamembranal portion of the M2 matrix protein which has been identified in the motif-based search. Pull-down assays and co-immunoprecipitation experiments showed that caveolin-1 binds to M2. The data suggest, that Cav-1 modulates influenza virus A replication presumably based on M2/Cav-1 interaction. Conclusion As Cav-1 is involved in the human influenza A virus life cycle, the multifunctional protein and its interaction with M2 protein of human influenza A viruses represent a promising starting point for the search for antiviral agents.

  13. Long interspersed element-1 (LINE-1): passenger or driver in human neoplasms?

    Science.gov (United States)

    Rodić, Nemanja; Burns, Kathleen H

    2013-03-01

    LINE-1 (L1) retrotransposons make up a significant portion of human genomes, with an estimated 500,000 copies per genome. Like other retrotransposons, L1 retrotransposons propagate through RNA sequences that are reverse transcribed into DNA sequences, which are integrated into new genomic loci. L1 somatic insertions have the potential to disrupt the transcriptome by inserting into or nearby genes. By mutating genes and playing a role in epigenetic dysregulation, L1 transposons may contribute to tumorigenesis. Studies of the "mobilome" have lagged behind other tumor characterizations at the sequence, transcript, and epigenetic levels. Here, we consider evidence that L1 retrotransposons may sometimes drive human tumorigenesis.

  14. FR-like EBNA1 binding repeats in the human genome

    International Nuclear Information System (INIS)

    D'Herouel, Aymeric Fouquier; Birgersdotter, Anna; Werner, Maria

    2010-01-01

    Epstein-Barr virus (EBV) is widely spread in the human population. EBV nuclear antigen 1 (EBNA1) is a transcription factor that activates viral genes and is necessary for viral replication and partitioning, which binds the EBV genome cooperatively. We identify similar EBNA1 repeat binding sites in the human genome using a nearest-neighbor positional weight matrix. Previously experimentally verified EBNA1 sites in the human genome are successfully recovered by our approach. Most importantly, 40 novel regions are identified in the human genome, constituted of tandemly repeated binding sites for EBNA1. Genes located in the vicinity of these regions are presented as possible targets for EBNA1-mediated regulation. Among these, four are discussed in more detail: IQCB1, IMPG1, IRF2BP2 and TPO. Incorporating the cooperative actions of EBNA1 is essential when identifying regulatory regions in the human genome and we believe the findings presented here are highly valuable for the understanding of EBV-induced phenotypic changes.

  15. Sympathomimetic Effects of Acute E-Cigarette Use: Role of Nicotine and Non-Nicotine Constituents.

    Science.gov (United States)

    Moheimani, Roya S; Bhetraratana, May; Peters, Kacey M; Yang, Benjamin K; Yin, Fen; Gornbein, Jeffrey; Araujo, Jesus A; Middlekauff, Holly R

    2017-09-20

    Chronic electronic (e) cigarette users have increased resting cardiac sympathetic nerve activity and increased susceptibility to oxidative stress. The purpose of the present study is to determine the role of nicotine versus non-nicotine constituents in e-cigarette emissions in causing these pathologies in otherwise healthy humans. Thirty-three healthy volunteers who were not current e-cigarette or tobacco cigarette smokers were studied. On different days, each participant used an e-cigarette with nicotine, an e-cigarette without nicotine, or a sham control. Cardiac sympathetic nerve activity was determined by heart rate variability, and susceptibility to oxidative stress was determined by plasma paraoxonase activity. Following exposure to the e-cigarette with nicotine, but not to the e-cigarette without nicotine or the sham control, there was a significant and marked shift in cardiac sympathovagal balance towards sympathetic predominance. The decrease in high-frequency component and the increases in the low-frequency component and the low-frequency to high-frequency ratio were significantly greater following exposure to the e-cigarette with nicotine compared with exposure to the e-cigarette without nicotine or to sham control. Oxidative stress, as estimated by plasma paraoxonase, did not increase following any of the 3 exposures. The acute sympathomimetic effect of e-cigarettes is attributable to the inhaled nicotine, not to non-nicotine constituents in e-cigarette aerosol, recapitulating the same heart rate variability pattern associated with increased cardiac risk in multiple populations with and without known cardiac disease. Evidence of oxidative stress, as estimated by plasma paraoxonase activity, was not uncovered following acute e-cigarette exposure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  16. Kidneys From α1,3-Galactosyltransferase Knockout/Human Heme Oxygenase-1/Human A20 Transgenic Pigs Are Protected From Rejection During Ex Vivo Perfusion With Human Blood.

    Science.gov (United States)

    Ahrens, Hellen E; Petersen, Björn; Ramackers, Wolf; Petkov, Stoyan; Herrmann, Doris; Hauschild-Quintern, Janet; Lucas-Hahn, Andrea; Hassel, Petra; Ziegler, Maren; Baars, Wiebke; Bergmann, Sabine; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

    2015-07-01

    Multiple modifications of the porcine genome are required to prevent rejection after pig-to-primate xenotransplantation. Here, we produced pigs with a knockout of the α1,3-galactosyltransferase gene (GGTA1-KO) combined with transgenic expression of the human anti-apoptotic/anti-inflammatory molecules heme oxygenase-1 and A20, and investigated their xenoprotective properties. The GGTA1-KO/human heme oxygenase-1 (hHO-1)/human A20 (hA20) transgenic pigs were produced in a stepwise approach using zinc finger nuclease vectors targeting the GGTA1 gene and a Sleeping Beauty vector coding for hA20. Two piglets were analyzed by quantitative reverse-transcription polymerase chain reaction, flow cytometry, and sequencing. The biological function of the genetic modifications was tested in a (51)Chromium release assay and by ex vivo kidney perfusions with human blood. Disruption of the GGTA1 gene by deletion of few basepairs was demonstrated in GGTA1-KO/hHO-1/hA20 transgenic pigs. The hHO-1 and hA20 mRNA expression was confirmed by quantitative reverse-transcription polymerase chain reaction. Ex vivo perfusion of 2 transgenic kidneys was feasible for the maximum experimental time of 240 minutes without symptoms of rejection. Results indicate that GGTA1-KO/hHO-1/hA20 transgenic pigs are a promising model to alleviate rejection and ischemia-reperfusion damage in porcine xenografts and could serve as a background for further genetic modifications toward the production of a donor pig that is clinically relevant for xenotransplantation.

  17. Syncytin-1 in differentiating human myoblasts

    DEFF Research Database (Denmark)

    Bjerregard, Bolette; Ziomkiewicz, Iwona; Schulz, Alexander

    2014-01-01

    Myoblasts fuse to form myotubes, which mature into skeletal muscle fibres. Recent studies indicate that an endogenous retroviral fusion gene, syncytin-1, is important for myoblast fusions in man. We have now expanded these data by examining the immunolocalization of syncytin in human myoblasts...... fusions. Thus, syncytin is involved in human myoblast fusions and is localized in areas of contact between fusing cells. Moreover, syncytin and caveolin-3 might interact at the level of the sarcolemma....

  18. Long interspersed element-1 (LINE-1: passenger or driver in human neoplasms?

    Directory of Open Access Journals (Sweden)

    Nemanja Rodić

    2013-03-01

    Full Text Available LINE-1 (L1 retrotransposons make up a significant portion of human genomes, with an estimated 500,000 copies per genome. Like other retrotransposons, L1 retrotransposons propagate through RNA sequences that are reverse transcribed into DNA sequences, which are integrated into new genomic loci. L1 somatic insertions have the potential to disrupt the transcriptome by inserting into or nearby genes. By mutating genes and playing a role in epigenetic dysregulation, L1 transposons may contribute to tumorigenesis. Studies of the "mobilome" have lagged behind other tumor characterizations at the sequence, transcript, and epigenetic levels. Here, we consider evidence that L1 retrotransposons may sometimes drive human tumorigenesis.

  19. Bovine brain ribonuclease is the functional homolog of human ribonuclease 1.

    Science.gov (United States)

    Eller, Chelcie H; Lomax, Jo E; Raines, Ronald T

    2014-09-19

    Mounting evidence suggests that human pancreatic ribonuclease (RNase 1) plays important roles in vivo, ranging from regulating blood clotting and inflammation to directly counteracting tumorigenic cells. Understanding these putative roles has been pursued with continual comparisons of human RNase 1 to bovine RNase A, an enzyme that appears to function primarily in the ruminant gut. Our results imply a different physiology for human RNase 1. We demonstrate distinct functional differences between human RNase 1 and bovine RNase A. Moreover, we characterize another RNase 1 homolog, bovine brain ribonuclease, and find pronounced similarities between that enzyme and human RNase 1. We report that human RNase 1 and bovine brain ribonuclease share high catalytic activity against double-stranded RNA substrates, a rare quality among ribonucleases. Both human RNase 1 and bovine brain RNase are readily endocytosed by mammalian cells, aided by tight interactions with cell surface glycans. Finally, we show that both human RNase 1 and bovine brain RNase are secreted from endothelial cells in a regulated manner, implying a potential role in vascular homeostasis. Our results suggest that brain ribonuclease, not RNase A, is the true bovine homolog of human RNase 1, and provide fundamental insight into the ancestral roles and functional adaptations of RNase 1 in mammals. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Effect of Some Dithiocarbamate Compounds in Irradiated Rats: Mechanism of Action

    International Nuclear Information System (INIS)

    Moustafa, E.M.M.

    2013-01-01

    The objective of this study is to give more information about the role of dithiocarbamates as antioxidant in radiation-protection. Three dithiocarbamates were selected: diethyldithiocarbamate (DEDC), thiram (TD) and dimethyldithiocarbamate (DMDC). Irradiation was performed by whole body exposure of rats to 1Gy of γ-irradiation 3 times /week up to a total dose of 9 Gy. Irradiated rats received, via gavages, 100 mg/Kg body weight, of the selected dithiocarbamates, 30 min before exposure to each dose. Animals were sacrificed at 2 weeks and 3 weeks after the last irradiation dose. The results obtained in animals treated with Thiram or its metabolite dimethyldithiocarbamate (DMDC) and combination with γ-radiation showed dramatic results of all parameters and revealed synergistic effect of combination between them. Sever antioxidant and detoxification enzyme depletion. Beside DNA fragmentation was highly recognized in tail DNA % (comet assay), in addition to deterioration in liver enzymes. On the other hand, Diethyl dithiocarbamates has significantly ameliorated radiation-induced oxidative stress in brain and liver tissues. The activity levels of the antioxidant enzymes reduced glutathione (GSH) content, glutathione peroxidase (GSH-Px) and glutathione reductase (GR), the superoxide dismutase (SOD) and catalase (CAT) were significantly ameliorated associated with a significant decrease in malondialdehyde (MDA) level. In addition, the administration of diethyldithiocarbamate has significantly ameliorated the radiation-induced changes in the activity of the detoxifying enzymes; glutathione-S-transferase (GST), acetylcholinesterase (AChE), paraoxonase (PON), arylesterase (AE), and carboxylesterase activity (CE) which tends to record normal values. Diethyldithiocarbamate have also shown protection against the radiation-induced deoxyribonucleic acid (DNA) fragmentation level. However, DEDT at low doses was the more efficient in radiation protection.

  1. Production of glycosylated physiologically normal human α1-antitrypsin by mouse fibroblasts modified by insertion of a human α1-antitrypsin cDNA using a retroviral vector

    International Nuclear Information System (INIS)

    Garver, R.I. Jr.; Chytil, A.; Karlsson, S.

    1987-01-01

    α 2 -Antitrypsin (α 1 AT) deficiency is a hereditary disorder characterized by reduced serum levels of α 1 AT, resulting in destruction of the lower respiratory tract by neutrophil elastase. As an approach to augment α 1 AT levels in this disorder with physiologically normal human α 1 AT, the authors have integrated a full-length normal human α 1 AT cDNA into the genome of mouse fibroblasts. To accomplish this, the retroviral vector N2 was modified by inserting the simian virus 40 early promoter followed by the α 1 AT cDNA. Southern analysis demonstrated that the intact cDNA was present in the genome of selected clones of the transfected murine fibroblasts psi2 and infected NIH 3T3. The clones produced three mRNA transcripts containing human α 1 AT sequences, secreted an α 1 AT molecule recognized by an anti-human α 1 AT antibody, with the same molecular mass as normal human α 1 AT and that complexed with and inhibited human neutrophil elastase. The psi2 produced α 1 AT was glycosylated, and when infused intravenously into mice, it had a serum half-life similar to normal α 1 AT purified from human plasma and markedly longer than that of nonglycosylated human α 1 AT cDNA-directed yeast-produced α 1 AT. These studies demonstrate the feasibility of using a retroviral vector to insert the normal human α 1 AT cDNA into non-α 1 AT-producing cells, resulting in the synthesis and secretion of physiologically normal α 1 AT

  2. Recombination in the human Pseudoautosomal region PAR1.

    Directory of Open Access Journals (Sweden)

    Anjali G Hinch

    2014-07-01

    Full Text Available The pseudoautosomal region (PAR is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome.

  3. Prevalence of human papilloma virus and human herpes virus types 1-7 in human nasal polyposis.

    Science.gov (United States)

    Zaravinos, Apostolos; Bizakis, John; Spandidos, Demetrios A

    2009-09-01

    This study aimed to investigate the prevalence of human papilloma virus (HPV), herpes simplex virus-1/-2 (HSV-1/-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6/-7 (HHV-6/-7) in 23 human nasal polyps by applying PCR. Two types of control tissues were used: adjacent inferior/middle turbinates from the patients and inferior/middle turbinates from 13 patients undergoing nasal corrective surgery. EBV was the virus most frequently detected (35%), followed by HPV (13%), HSV-1 (9%), and CMV (4%). The CMV-positive polyp was simultaneously positive for HSV-1. HPV was also detected in the adjacent turbinates (4%) and the adjacent middle turbinate (4%) of one of the HPV-positive patients. EBV, HSV, and CMV were not detected in the adjacent turbinates of the EBV-, HSV- or CMV-positive patients. All mucosae were negative for the VZV, HHV-6, and HHV-7. This is the first study to deal with the involvement of a comparable group of viruses in human nasal polyposis. The findings support the theory that the presence of viral EBV markedly influences the pathogenesis of these benign nasal tumors. The low incidence of HPV detected confirms the hypothesis that HPV is correlated with infectious mucosal lesions to a lesser extent than it is with proliferative lesions, such as inverted papilloma. The low incidence of HSV-1 and CMV confirms that these two herpes viruses may play a minor role in the development of nasal polyposis. Double infection with HSV-1 and CMV may also play a minor, though causative, role in nasal polyp development. VZV and HHV-6/-7 do not appear to be involved in the pathogenesis of these mucosal lesions.

  4. Peroxynitrite Sensor Based on a Screen Printed Carbon Electrode Modified with a Poly(2,6-dihydroxynaphthalene Film

    Directory of Open Access Journals (Sweden)

    Ioana Silvia Hosu

    2016-11-01

    Full Text Available For the first time the electropolymerization of 2,6-dihydroxynaphthalene (2,6-DHN on a screen printed carbon electrode (SPCE was investigated and evaluated for peroxynitrite (PON detection. Cyclic voltammetry was used to electrodeposit the poly(2,6-DHN on the carbon electrode surface. The surface morphology and structure of poly(2,6-DHN film were investigated by SEM and FTIR analysis, and the electrochemical features by cyclic voltammetry. The poly(2,6-DHN/SPCE sensor showed excellent electrocatalytic activity for PON oxidation in alkaline solutions at very low potentials (0–100 mV vs. Ag/AgCl pseudoreference. An amperometric FIA (flow injection analysis system based on the developed sensor was optimized for PON measurements and a linear concentration range from 2 to 300 μM PON, with a LOD of 0.2 μM, was achieved. The optimized sensor inserted in the FIA system exhibited good sensitivity (4.12 nA·μM−1, selectivity, stability and intra-/inter-electrode reproducibility for PON determination.

  5. New attenuation correction for the HRRT using transmission scatter correction and total variation regularization

    DEFF Research Database (Denmark)

    Sibomana, Merence; Keller, Sune Høgild; Svarer, Claus

    2009-01-01

    on emission images reconstructed with the new TXTV and old MAP-TR μ-maps to images reconstructed with co-registered CT-based μ-maps on four 18F FDG scans. The CT μ-maps is considered a gold standard. The comparison show a significant decrease in the bias in cerebellum and pons, and a better agreement between......In the standard software for the Siemens HRRT PET scanner the most commonly used segmentation in the μ-map reconstruction for human brain scans is MAP-TR. Problems with bias in the lower cerebellum and pons in HRRT brain images have been reported. The main source of the problem is poor bone / soft...

  6. Oxidative Stress and Inflammation Differentially Elevated in Objective Versus Habitual Subjective Reduced Sleep Duration in Obstructive Sleep Apnea.

    Science.gov (United States)

    DeMartino, Theresanne; Ghoul, Rawad El; Wang, Lu; Bena, James; Hazen, Stanley L; Tracy, Russel; Patel, Sanjay R; Auckley, Dennis; Mehra, Reena

    2016-07-01

    Data have demonstrated adverse health effects of sleep deprivation. We postulate that oxidative stress and systemic inflammation biomarkers will be elevated in relation to short-term and long-term sleep duration reduction. We analyzed data from the baseline examination of a randomized controlled trial involving participants with moderate to severe obstructive sleep apnea (OSA). Baseline polysomnography provided the total sleep time (PSG-TST, primary predictor); self-reported habitual sleep duration (SR-HSD) data was collected. Morning measures of oxidative stress and systemic inflammation included: myeloperoxidase (MPO, pmol/L), oxidized low-density lipoprotein (ox-LDL, U/L), F2-isoprostane (ng/mg), paraoxonase 1 (PON1, nmol·min(-1)·mL(-1)), and aryl esterase (μmol·min(-1)·mL(-1)). Linear models adjusted for age, sex, race, body mass index (BMI), cardiovascular disease (CVD), smoking, statin/anti-inflammatory medications, and apnea-hypopnea index were utilized (beta estimates and 95% confidence intervals). One hundred forty-seven participants comprised the final analytic sample; they were overall middle-aged (51.0 ± 11.7 y), obese (BMI = 37.3 ± 8.1 kg/m(2)), and 17% had CVD. Multivariable models demonstrated a significant inverse association of PSG-TST and MPO (β [95% CI] = -20.28 [-37.48, -3.08], P = 0.021), i.e., 20.3 pmol/L MPO reduction per hour increase PSG-TST. Alternatively, a significant inverse association with ox-LDL and SR-HSD was observed (β [95% CI] = 0.98 [0.96, 0.99], P = 0.027), i.e., 2% ox-LDL reduction per hour increase SR-HSD. Even after consideration of obesity and OSA severity, inverse significant findings were observed such that reduced PSG-TST was associated with elevated MPO levels and SR-HSD with ox-LDL, suggesting differential up-regulation of oxidative stress and pathways of inflammation in acute versus chronic sleep curtailment. NIH clinical trials registry number NCT00607893. © 2016 Associated Professional Sleep Societies, LLC.

  7. A Comparative Study of Multiplexing Schemes for Next Generation Optical Access Networks

    Science.gov (United States)

    Imtiaz, Waqas A.; Khan, Yousaf; Shah, Pir Mehar Ali; Zeeshan, M.

    2014-09-01

    Passive optical network (PON) is a high bandwidth, economical solution which can provide the necessary bandwidth to end-users. Wavelength division multiplexed passive optical networks (WDM PONs) and time division multiplexed passive optical networks (TDM PONs) are considered as an evolutionary step for next-generation optical access (NGOA) networks. However they fail to provide highest transmission capacity, efficient bandwidth access, and robust dispersion tolerance. Thus future PONs are considered on simpler, efficient and potentially scalable, optical code division multiplexed (OCDM) PONs. This paper compares the performance of existing PONs with OCDM PON to determine a suitable scheme for NGOA networks. Two system parameter are used in this paper: fiber length, and bit rate. Performance analysis using Optisystem shows that; for a sufficient system performance parameters i.e. bit error rate (BER) ≤ 10-9, and maximum quality factor (Q) ≥ 6, OCDMA PON efficiently performs upto 50 km with 10 Gbit/s per ONU.

  8. SHARP1: A revised systematic human action reliability procedure

    International Nuclear Information System (INIS)

    Wakefield, D.J.; Parry, G.W.; Hannaman, G.W.; Spurgin, A.J.

    1990-12-01

    Individual plant examinations (IPE) are being performed by utilities to evaluate plant-specific vulnerabilities to severe accidents. A major tool in performing an IPE is a probabilistic risk assessment (PRA). The importance of human interactions in determining the plant response in past PRAs is well documented. The modeling and quantification of the probabilities of human interactions have been the subjects of considerable research by the Electric Power Research Institute (EPRI). A revised framework, SHARP1, for incorporating human interactions into PRA is summarized in this report. SHARP1 emphasizes that the process stages are iterative and directed at specific goals rather than being performed sequentially in a stepwise procedure. This expanded summary provides the reader with a flavor of the full report content. Excerpts from the full report are presented, following the same outline as the full report. In the full report, the interface of the human reliability analysis with the plant logic model development in a PRA is given special attention. In addition to describing a methodology framework, the report also discusses the types of human interactions to be evaluated, and how to formulate a project team to perform the human reliability analysis. A concise description and comparative evaluation of the selected existing methods of quantification of human error are also presented. Four case studies are also provided to illustrate the SHARP1 process

  9. Crystal structure of the human 4-1BB/4-1BBL complex.

    Science.gov (United States)

    Gilbreth, Ryan N; Oganesyan, Vaheh Y; Amdouni, Hamza; Novarra, Shabazz; Grinberg, Luba; Barnes, Arnita; Baca, Manuel

    2018-05-02

    4-1BBL is a member of the TNF superfamily and is the ligand for the TNFRsuperfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells and agonists of this receptor have garnered strong attention as potentialimmunotherapy agents. Broadly speaking, the structural features of TNF superfamilymembers, their receptors and ligand/receptor complexes are similar. However, apublished crystal structure of human 4-1BBL suggests that it may be unique in thisregard, exhibiting a three-bladed propeller-like trimer assembly that is distinctly different from that observed in other family members. This unusual structure also suggests that the human 4-1BB/4-1BBL complex may be structurally unique within the TNF/TNFR superfamily, but to date no structural data have been reported. Here we report the crystal structure of the human 4-1BB/4-1BBL complex at 2.4 Å resolution. In this structure, 4-1BBL does not adopt the unusual trimer assembly previously reported, but instead forms a canonical bell-shaped trimer typical of other TNF superfamily members. The structure of 4-1BB is also largely canonical as is the 4-1BB/4-1BBL complex. Mutational data support the 4-1BBL structure reported here as being biologically relevant, suggesting that the previously reported structure is not. Together, the data presented here offer insight into structure/function relationships in the 4-1BB/4-1BBL system and improve our structural understanding of the TNF/TNFR superfamily more broadly. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Triton X-114 cloud point extraction to subfractionate blood plasma proteins for two-dimensional gel electrophoresis

    DEFF Research Database (Denmark)

    Jessen, Flemming; Wulff, Tune

    2015-01-01

    -sterol acyltransferase, serum amyloid A, and serum paraoxonase/arylesterase 1, which are proteins of a hydrophobic nature, as in plasma they relate to lipoprotein particles. Thus, Triton X-114-based CPE is a simple plasma prefractionation tool, attractive for detailed 2DE studies of hydrophobic plasma proteins...

  11. FINE SPECIFICITY OF CELLULAR IMMUNE-RESPONSES IN HUMANS TO HUMAN CYTOMEGALOVIRUS IMMEDIATE-EARLY 1-PROTEIN

    NARCIS (Netherlands)

    ALP, NJ; ALLPORT, TD; VANZANTEN, J; RODGERS, B; SISSONS, JGP; BORYSIEWICZ, LK

    Cell-mediated immunity is important in maintaining the virus-host equilibrium in persistent human cytomegalovirus (HCMV) infection. The HCMV 72-kDa major immediate early 1 protein (IE1) is a target for CD8+ cytotoxic T cells in humans, as is the equivalent 89-kDa protein in mouse. Less is known

  12. Expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) in human cholesteatoma.

    Science.gov (United States)

    Lee, No Hee; Chang, Ji-Won; Choi, June; Jung, Hak Hyun; Im, Gi Jung

    2013-02-01

    Ras-related C3 botulinum toxin substrate 1 (RAC1) is a 21-kDa signaling G protein that functions as a pleiotropic regulator of many cellular processes including epithelial differentiation. RAC1 activates the nicotinamide adenine dinucleotide phosphate oxidase complex which promotes formation of reactive oxygen species and degradation enzymes. RAC1 has been associated with rapid epithelial differentiation and invasive properties in human cholesteatoma. This study aimed to identify the presence of RAC1 in human cholesteatoma and analyze its functional role as a regulator of proteolysis and overgrowth. Tissue samples from human cholesteatoma and normal postaural skin were obtained from patients during otologic surgery for cholesteatoma. The expression of RAC1 mRNA was quantified by real-time RT-PCR, and localization of RAC1 expression was confirmed using immunohistochemical staining. Expression of RAC1 mRNA in the epithelium of cholesteatoma was significantly elevated 2.94 fold on average, compared with normal control skin. RAC1 expression in the suprabasal and basal layer of cholesteatoma epithelium was stronger than normal control skin. Our results suggest that RAC1 can be associated with rapid epithelial differentiation and invasive properties of human cholesteatoma.

  13. Effect of nitrogen source in the fertilizing solution on nutritional quality of three members of the Portulaca oleracea aggregate.

    Science.gov (United States)

    Szalai, Gabriella; Dai, Nir; Danin, Avinoam; Dudai, Nativ; Barazani, Oz

    2010-09-01

    Portulaca oleracea (purslane) is nutritious but, in addition to the essential alpha-linolenic acid, vitamin C and tocopherols, it contains undesirable oxalic acid. Knowing the effects of nitrate and ammonium on oxalate accumulation, we tested the agronomic potential of three members of the P. oleracea aggregate under various nitrogen fertilization conditions, by measuring biomass production and accumulation of fatty acids, organic acids and tocopherol in the commercial P. sativa (Pos) and two natural members: P. nitida (Pon) and P. papillato-stellulata (Pop). With nitrate as the sole N source, we measured differences between Pon and Pos in concentrations of the essential omega-3 fatty acid alpha-linolenic acid. Pos also gained less dry biomass under these conditions, implying a higher agronomical and nutritional value for Pon. Increasing the fertilizer ammonium concentration and reducing that of nitrate significantly decreased oxalic acid by factors of up to 1.7, 2.6 and 3.4 in Pos, Pop and Pon, respectively, significantly increased concentrations of tocopherol and malic acid, had no effect on fatty acids or ascorbic acid, but reduced biomass. In spite of the recumbent growth habit of Pon, the present findings indicate its agronomic potential. Because early flowering and seed production may be the limiting factors in purslane agriculture, growing Pon in nitrate-poor conditions might be agriculturally favorable. Copyright 2010 Society of Chemical Industry.

  14. AHR prevents human IL-1R1hi ILC3 differentiation to natural killer cells

    Science.gov (United States)

    Hughes, Tiffany; Briercheck, Edward L.; Freud, Aharon G.; Trotta, Rossana; McClory, Susan; Scoville, Steven D.; Keller, Karen; Deng, Youcai; Cole, Jordan; Harrison, Nicholas; Mao, Charlene; Zhang, Jianying; Benson, Don M.; Yu, Jianhua; Caligiuri, Michael A.

    2014-01-01

    SUMMARY Accumulating evidence indicates that human natural killer (NK) cells develop in secondary lymphoid tissue (SLT) through a so-called “stage 3” developmental intermediate minimally characterized by a CD34-CD117+CD94- immunophenotype that lacks mature NK cell function. This stage 3 population is heterogeneous, potentially composed of functionally distinct innate lymphoid cell (ILC) types that includes interleukin-1 receptor (IL-1R1) positive, IL-22-producing ILC3s. Whether human ILC3s are developmentally related to NK cells is a subject of ongoing investigation. Here we show that antagonism of the aryl hydrocarbon receptor (AHR) or silencing of AHR gene expression promotes differentiation of tonsillar IL-22-producing IL-1R1hi human ILC3s to CD56brightCD94+ IFN-gamma-producing cytolytic mature NK cells expressing eomesodermin (EOMES) and T-Box Protein 21 (TBX21 or TBET). Hence, AHR is a transcription factor that prevents human IL-1R1hi ILC3s from differentiating into NK cells. PMID:24953655

  15. Human Parechovirus 1 Infection Occurs via αVβ1 Integrin.

    Directory of Open Access Journals (Sweden)

    Pirjo Merilahti

    Full Text Available Human parechovirus 1 (HPeV-1 (family Picornaviridae is a global cause of pediatric respiratory and CNS infections for which there is no treatment. Although biochemical and in vitro studies have suggested that HPeV-1 binds to αVβ1, αVβ3 and αVβ6 integrin receptor(s, the actual cellular receptors required for infectious entry of HPeV-1 remain unknown. In this paper we analyzed the expression profiles of αVβ1, αVβ3, αVβ6 and α5β1 in susceptible cell lines (A549, HeLa and SW480 to identify which integrin receptors support HPeV-1 internalization and/or replication cycle. We demonstrate by antibody blocking assay, immunofluorescence microscopy and RT-qPCR that HPeV-1 internalizes and replicates in cell lines that express αVβ1 integrin but not αVβ3 or αVβ6 integrins. To further study the role of β1 integrin, we used a mouse cell line, GE11-KO, which is deficient in β1 expression, and its derivate GE11-β1 in which human integrin β1 subunit is overexpressed. HPeV-1 (Harris strain and three clinical HPeV-1 isolates did not internalize into GE11-KO whereas GE11-β1 supported the internalization process. An integrin β1-activating antibody, TS2/16, enhanced HPeV-1 infectivity, but infection occurred in the absence of visible receptor clustering. HPeV-1 also co-localized with β1 integrin on the cell surface, and HPeV-1 and β1 integrin co-endocytosed into the cells. In conclusion, our results demonstrate that in some cell lines the cellular entry of HPeV-1 is primarily mediated by the active form of αVβ1 integrin without visible receptor clustering.

  16. Human-system interface design review guideline -- Process and guidelines: Final report. Revision 1, Volume 1

    International Nuclear Information System (INIS)

    1996-06-01

    NUREG-0700, Revision 1, provides human factors engineering (HFE) guidance to the US Nuclear Regulatory Commission staff for its: (1) review of the human system interface (HSI) design submittals prepared by licensees or applications for a license or design certification of commercial nuclear power plants, and (2) performance of HSI reviews that could be undertaken as part of an inspection or other type of regulatory review involving HSI design or incidents involving human performance. The guidance consists of a review process and HFE guidelines. The document describes those aspects of the HSI design review process that are important to the identification and resolution of human engineering discrepancies that could adversely affect plant safety. Guidance is provided that could be used by the staff to review an applicant's HSI design review process or to guide the development of an HSI design review plan, e.g., as part of an inspection activity. The document also provides detailed HFE guidelines for the assessment of HSI design implementations. NUREG-0700, Revision 1, consists of three stand-alone volumes. Volume 1 consists of two major parts. Part 1 describes those aspects of the review process of the HSI design that are important to identifying and resolving human engineering discrepancies. Part 2 contains detailed guidelines for a human factors engineering review which identify criteria for assessing the implementation of an applicant's or licensee's HSI design

  17. Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children

    Energy Technology Data Exchange (ETDEWEB)

    Rossi Espagnet, Maria Camilla; Bernardi, Bruno; Figa-Talamanca, Lorenzo [Ospedale Pediatrico Bambino Gesu, IRCCS, Neuroradiology Unit, Imaging Department, Rome (Italy); Pasquini, Luca [Ospedale Pediatrico Bambino Gesu, IRCCS, Neuroradiology Unit, Imaging Department, Rome (Italy); University Sapienza, Neuroradiology Unit, Azienda Ospedaliera Sant' Andrea, Rome (Italy); Toma, Paolo [Ospedale Pediatrico Bambino Gesu, IRCCS, Department of Imaging, Rome (Italy); Napolitano, Antonio [Ospedale Pediatrico Bambino Gesu, IRCCS, Enterprise Risk Management, Medical Physics Department, Rome (Italy)

    2017-09-15

    Few studies have been conducted on the relations between T1-weighted signal intensity changes in the pediatric brain following gadolinium-based contrast agent (GBCA) exposure. The purpose of this study is to investigate the effect of multiple administrations of a macrocyclic GBCA on signal intensity in the globus pallidus and dentate nucleus of the pediatric brain on unenhanced T1-weighted MR images. This retrospective study included 50 patients, mean age: 8 years (standard deviation: 4.8 years), with normal renal function exposed to ≥6 administrations of the same macrocyclic GBCA (gadoterate meglumine) and a control group of 59 age-matched GBCA-naive patients. The globus pallidus-to-thalamus signal intensity ratio and dentate nucleus-to-pons signal intensity ratio were calculated from unenhanced T1-weighted images for both patients and controls. A mixed linear model was used to evaluate the effects on signal intensity ratios of the number of GBCA administrations, the time interval between administrations, age, radiotherapy and chemotherapy. T-test analyses were performed to compare signal intensity ratio differences between successive administrations and baseline MR signal intensity ratios in patients compared to controls. P-values were considered significant if <0.05. A significant effect of the number of GBCA administrations on relative signal intensities globus pallidus-to-thalamus (F[8]=3.09; P=0.002) and dentate nucleus-to-pons (F[8]=2.36; P=0.021) was found. The relative signal intensities were higher at last MR examination than at baseline (P<0.001). Quantitative analysis evaluation of globus pallidus:thalamus and dentate nucleus:pons of the pediatric brain demonstrated an increase after serial administrations of macrocyclic GBCA. Further research is necessary to fully understand GBCA pharmacokinetic in children. (orig.)

  18. Alternative splicing of cyclooxygenase-1 mRNA in the human iris

    NARCIS (Netherlands)

    Dröge, M.J; van Sorge, A.A; van Haeringen, N.J; Quax, Wim; Zaagsma, Hans; Droge, MJ

    2003-01-01

    dIn homogenates of the human iris, the nonsteroidal antiinflammatory drug (NSAID) S(+)flurbiprofen has been reported to inhibit cyclooxygenase-1 (COX-1) 70-fold more potently than in human whole blood. We hypothesized that this difference may be due to alternative splicing of COX-1 mRNA in the human

  19. Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation.

    Directory of Open Access Journals (Sweden)

    Lianghua Bin

    Full Text Available The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq profiling approach, we found that forkhead box c 1 (FOXC1 was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network.

  20. Human Nav1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons

    Science.gov (United States)

    Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D.

    2015-01-01

    Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Nav1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Nav1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Nav1.8 channels. We also show that native human DRG neurons recapitulate these properties of Nav1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Nav1.8, which contribute to the firing properties of human DRG neurons. PMID:25787950

  1. Activated human mast cells induce LOX-1-specific scavenger receptor expression in human monocyte-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Mervi Alanne-Kinnunen

    Full Text Available Activated mast cells in atherosclerotic lesions degranulate and release bioactive compounds capable of regulating atherogenesis. Here we examined the ability of activated human primary mast cells to regulate the expression of the major scavenger receptors in cultured human primary monocyte-derived macrophages (HMDMs.Components released by immunologically activated human primary mast cells induced a transient expression of lectin-like oxidized LDL receptor (LOX-1 mRNA in HMDMs, while the expression of two other scavenger receptors, MSR1 and CD36, remained unaffected. The LOX-1-inducing secretory components were identified as histamine, tumor necrosis factor alpha (TNF-α, and transforming growth factor beta (TGF-β1, which exhibited a synergistic effect on LOX-1 mRNA expression. Histamine induced a transient expression of LOX-1 protein. Mast cell -induced increase in LOX-1 expression was not associated with increased uptake of oxidized LDL by the macrophages.Mast cell-derived histamine, TNF-α, and TGF-β1 act in concert to induce a transient increase in LOX-1 expression in human primary monocyte-derived macrophages. The LOX-1-inducing activity potentially endows mast cells a hitherto unrecognized role in the regulation of innate immune reactions in atherogenesis.

  2. Whole genome analysis of Klebsiella pneumoniae T2-1-1 from human oral cavity

    Directory of Open Access Journals (Sweden)

    Kok-Gan Chan

    2016-03-01

    Full Text Available Klebsiella pneumoniae T2-1-1 was isolated from the human tongue debris and subjected to whole genome sequencing on HiSeq platform and annotated on RAST. The nucleotide sequence of this genome was deposited into DDBJ/EMBL/GenBank under the accession JAQL00000000. Keywords: Human tongue surface, Oral cavity, Oral bacteria, Virulence

  3. SYNERGISTIC EFFECTS OF NOVOLAC-BASED CHAR FORMER WITH A PHOSPHORUS/NITROGEN-CONTAINING FLAME RETARDANT IN POLYAMIDE 6

    Institute of Scientific and Technical Information of China (English)

    Wei-cheng Xiong; Li Chen; De-yi Wang; Fei Song; Yu-zhong Wang

    2012-01-01

    The synergistic effect of phosphorus oxynitride (PON) with a novolac-based char former modified by salification (NA-metal salt) on the flame retardance of polyamide 6 (PA6) was investigated.For this purpose,various flame-retardant PA6 systems were melt-compounded with PON,PON/NA,PON/NA-V2O5 and PON/NA-Fe2O3,and their flame retardance was evaluated by measuring the limiting oxygen index (LOI) values and UL-94 vertical burning ratings.The results showed that,compared with the PA6/PON/NA system,the combination of two char formers (NA-V2O5,NA-Fe2O3) with PON could obviously improve the char formation and flame retardance of PA6.The flame retardance and cone calorimetric analyses showed the stronger synergism as well as the better flame retardant performance of PON/NA-Fe2O3 flame retardant system.The effects of different char formers on the flame retardance and thermal stability of this system were also discussed.

  4. HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases

    International Nuclear Information System (INIS)

    Devroe, Eric; Silver, Pamela A.; Engelman, Alan

    2005-01-01

    Mammalian genomes encode two related serine-threonine kinases, nuclear Dbf2 related (NDR)1 and NDR2, which are homologous to the Saccharomyces cerevisiae Dbf2 kinase. Recently, a yeast genetic screen implicated the Dbf2 kinase in Ty1 retrotransposition. Since several virion-incorporated kinases regulate the infectivity of human immunodeficiency virus type 1 (HIV-1), we speculated that the human NDR1 and NDR2 kinases might play a role in the HIV-1 life cycle. Here we show that the NDR1 and NDR2 kinases were incorporated into HIV-1 particles. Furthermore, NDR1 and NDR2 were cleaved by the HIV-1 protease (PR), both within virions and within producer cells. Truncation at the PR cleavage site altered NDR2 subcellular localization and inhibited NDR1 and NDR2 enzymatic activity. These studies identify two new virion-associated host cell enzymes and suggest a novel mechanism by which HIV-1 alters the intracellular environment of human cells

  5. Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3.

    Science.gov (United States)

    Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

    2014-01-01

    The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system.

  6. Human CYP2E1 mediates the formation of glycidamide from acrylamide

    Energy Technology Data Exchange (ETDEWEB)

    Settels, Eva; Appel, Klaus E. [Federal Institute for Risk Assessment, Center for Experimental Toxicology, Berlin (Germany); Bernauer, Ulrike; Gundert-Remy, Ursula [Federal Institute for Risk Assessment, Department of Safety of Substances and Preparations, Berlin (Germany); Palavinskas, Richard; Klaffke, Horst S. [Federal Institute for Risk Assessment, Center for Analytical Chemistry, Berlin (Germany)

    2008-10-15

    Regarding the cancer risk assessment of acrylamide (AA) it is of basic interest to know, as to what amount of the absorbed AA is metabolized to glycidamide (GA) in humans, compared to what has been observed in laboratory animals. GA is suspected of being the ultimate carcinogenic metabolite of AA. From experiments with CYP2E1-deficient mice it can be concluded that AA is metabolized to GA primarily by CYP2E1. We therefore examined whether CYP2E1 is involved in GA formation in non-rodent species with the focus on humans by using human CYP2E1 supersomes trademark, marmoset and human liver microsomes and in addition, genetically engineered V79 cells expressing human CYP2E1 (V79h2E1 cells). Special emphasis was placed on the analytical detection of GA, which was performed by gas chromatography/mass spectrometry. The results show that AA is metabolized to GA in human CYP2E1 supersomes trademark, in marmoset and human liver microsomes as well as in V79h2E1 cells. The activity of GA formation is highest in supersomes trademark; in human liver it is somewhat higher than in marmoset liver. A monoclonal CYP2E1 human selective antibody (MAB-2E1) and diethyldithiocarbamate (DDC) were used as specific inhibitors of CYP2E1. The generation of GA could be inhibited by MAB-2E1 to about 80% in V79h2E1 cells and to about 90% in human and marmoset liver microsomes. Also DDC led to an inhibition of about 95%. In conclusion, AA is metabolized to GA by human CYP2E1. Overall, the present work describes (1) the application and refinement of a sensitive methodology in order to determine low amounts of GA, (2) the applicability of genetically modified V79 cell lines in order to investigate specific questions concerning metabolism and (3) the involvement, for the first time, of human CYP2E1 in the formation of GA from AA. Further studies will compare the activities of GA formation in genetically engineered V79 cells expressing CYP2E1 from different species. (orig.)

  7. Survivable architectures for time and wavelength division multiplexed passive optical networks

    Science.gov (United States)

    Wong, Elaine

    2014-08-01

    The increased network reach and customer base of next-generation time and wavelength division multiplexed PON (TWDM-PONs) have necessitated rapid fault detection and subsequent restoration of services to its users. However, direct application of existing solutions for conventional PONs to TWDM-PONs is unsuitable as these schemes rely on the loss of signal (LOS) of upstream transmissions to trigger protection switching. As TWDM-PONs are required to potentially use sleep/doze mode optical network units (ONU), the loss of upstream transmission from a sleeping or dozing ONU could erroneously trigger protection switching. Further, TWDM-PONs require its monitoring modules for fiber/device fault detection to be more sensitive than those typically deployed in conventional PONs. To address the above issues, three survivable architectures that are compliant with TWDM-PON specifications are presented in this work. These architectures combine rapid detection and protection switching against multipoint failure, and most importantly do not rely on upstream transmissions for LOS activation. Survivability analyses as well as evaluations of the additional costs incurred to achieve survivability are performed and compared to the unprotected TWDM-PON. Network parameters that impact the maximum achievable network reach, maximum split ratio, connection availability, fault impact, and the incremental reliability costs for each proposed survivable architecture are highlighted.

  8. PKCα expression regulated by Elk-1 and MZF-1 in human HCC cells

    International Nuclear Information System (INIS)

    Hsieh, Y.-H.; Wu, T.-T.; Tsai, J.-H.; Huang, C.-Y.; Hsieh, Y.-S.; Liu, J.-Y.

    2006-01-01

    Our previous study found that PKCα was highly expressed in the poor-differentiated human HCC cells and associated with cell migration and invasion. In this study, we further investigated the gene regulation of this enzyme. We showed that PKCα expression enhancement in the poor-differentiated human HCC cells was found neither by DNA amplification nor by increasing mRNA stability using differential PCR and mRNA decay assays. After screening seven transcription factors in the putative cis-acting regulatory elements of human PKCα promoters, only Elk-1 and MZF-1 antisense oligonucleotide showed a significant reduction in the PKCα mRNA level. They also reduced cell proliferation, cell migratory and invasive capabilities, and DNA binding activities in the PKCα promoter region. Over-expression assay confirmed that the PKCα expression may be modulated by these two factors at the transcriptional level. Therefore, these results may provide a novel mechanism for PKCα expression regulation in human HCC cells

  9. Mutation analysis of the MCHR1 gene in human obesity

    DEFF Research Database (Denmark)

    Wermter, Anne-Kathrin; Reichwald, Kathrin; Büch, Thomas

    2005-01-01

    The importance of the melanin-concentrating hormone (MCH) system for regulation of energy homeostasis and body weight has been demonstrated in rodents. We analysed the human MCH receptor 1 gene (MCHR1) with respect to human obesity....

  10. Human-system interface design review guideline -- Process and guidelines: Final report. Revision 1, Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    None

    1996-06-01

    NUREG-0700, Revision 1, provides human factors engineering (HFE) guidance to the US Nuclear Regulatory Commission staff for its: (1) review of the human system interface (HSI) design submittals prepared by licensees or applications for a license or design certification of commercial nuclear power plants, and (2) performance of HSI reviews that could be undertaken as part of an inspection or other type of regulatory review involving HSI design or incidents involving human performance. The guidance consists of a review process and HFE guidelines. The document describes those aspects of the HSI design review process that are important to the identification and resolution of human engineering discrepancies that could adversely affect plant safety. Guidance is provided that could be used by the staff to review an applicant`s HSI design review process or to guide the development of an HSI design review plan, e.g., as part of an inspection activity. The document also provides detailed HFE guidelines for the assessment of HSI design implementations. NUREG-0700, Revision 1, consists of three stand-alone volumes. Volume 1 consists of two major parts. Part 1 describes those aspects of the review process of the HSI design that are important to identifying and resolving human engineering discrepancies. Part 2 contains detailed guidelines for a human factors engineering review which identify criteria for assessing the implementation of an applicant`s or licensee`s HSI design.

  11. Cerebral A1 adenosine receptors (A1AR) in liver cirrhosis

    International Nuclear Information System (INIS)

    Boy, Christian; Meyer, Philipp T.; Kircheis, Gerald; Haussinger, Dieter; Holschbach, Marcus H.; Coenen, Heinz H.; Herzog, Hans; Elmenhorst, David; Kaiser, Hans J.; Zilles, Karl; Bauer, Andreas

    2008-01-01

    The cerebral mechanisms underlying hepatic encephalopathy (HE) are poorly understood. Adenosine, a neuromodulator that pre- and postsynaptically modulates neuronal excitability and release of classical neurotransmitters via A 1 adenosine receptors (A 1 AR), is likely to be involved. The present study investigates changes of cerebral A 1 AR binding in cirrhotic patients by means of positron emission tomography (PET) and [ 18 F]CPFPX, a novel selective A 1 AR antagonist. PET was performed in cirrhotic patients (n = 10) and healthy volunteers (n = 10). Quantification of in vivo receptor density was done by Logan's non-invasive graphical analysis (pons as reference region). The outcome parameter was the apparent binding potential (aBP, proportional to B max /K D ). Cortical and subcortical regions showed lower A 1 AR binding in cirrhotic patients than in controls. The aBP changes reached statistical significance vs healthy controls (p 1 AR binding may further aggravate neurotransmitter imbalance at the synaptic cleft in cirrhosis and hepatic encephalopathy. Different pathomechanisms may account for these alterations including decrease of A 1 AR density or affinity, as well as blockade of the A 1 AR by endogenous adenosine or exogenous xanthines. (orig.)

  12. Relación entre paraoxonasa, otros componentes de HDL y estado inflamatorio en hemodiálisis

    Directory of Open Access Journals (Sweden)

    Ana Inés González

    2010-12-01

    Full Text Available La enfermedad renal crónica (ERC se asocia estrechamente con un estado pro-inflamatorio, aumento de lipoproteínas ricas en triglicéridos y disminución de HDL. La HDL contiene enzimas antioxidantes asociadas como la paraoxonasa (PON, cuya actividad en ERC se encuentra disminuida. Nuestro objetivo fue evaluar la relación entre la actividad de PON, apoA1, colesterol(col-HDL y Proteína C reactiva-altamente sensible (PCR-as como marcador de inflamación en pacientes en hemodiálisis. Se estudiaron n = 42 pacientes; edad, mediana (rango = 50 (25-67 años; sexo M/F = 22/20; antigüedad de hemodiálisis = 4.4 ± 0.5 años; índice de masa corporal (IMC = 23 ± 0.5 kg/m². Se obtuvo una muestra de sangre después de 12 h de ayuno y se determinaron los parámetros clásicos del perfil lipídico, se midieron los valores de apoproteínas A1 y B, PON a través de su actividad arilesterasa y PCR-as, la cual permitió dividir a los pacientes con PCR-as ≤ 1 (bajo riesgo, rango: 0.1 a 1.0 mg/l y > 1 mg/l (moderado y alto riesgo, 1.1 a 10.7 mg/l. Los niveles de triglicéridos, col-LDL y apoB no fueron diferentes entre los grupos. Los pacientes con PCR-as > 1 presentaron menor col-HDL (40 ± 2 mg/dl y apoA1 (118 ± 4 mg/dl que los pacientes con PCR-as ≤ 1 (50 ± 4 y 133 ± 5, respectivamente; p 1: 90.5 ± 24.0 μmol/ml.min que en PCR-as ≤ 1: 105.2 ± 18.0. Consecuentemente, se obtuvieron correlaciones inversas entre apoA1 y PCR-as, r = -0.381 p = 0.013 y entre PON y PCR-as, r = -0.32, p = 0.042. Además, el aumento de PCR-as correlacionó positivamente con el IMC, r = 0.318, p = 0.042. La disminución de col-HDL, apoA1 y PON en los individuos con mayor estado inflamatorio explicaría, en parte, el aumento de riesgo cardiovascular de estos pacientes, dado los efectos antiinflamatorios de la apoA1 y antioxidantes de la PON.

  13. Genetically Engineered Mouse Model of Diffuse Intrinsic Pontine Glioma as a Preclinical Tool

    Science.gov (United States)

    2014-11-01

    www.actaneurocomms.org/content/2/1/134N-Myc and Hedgehog [17], MYCN, silent, and H3-K27M [10] or H3-K27M and wildtype [6]. Together, these classi...pons, and as there are significant differences between mouse and human brainstem anatomy , we can- not be certain that the dorsal Nestin+/Pax3...Fisher PG, Weissman IL, Rowitch DH, Vogel H, Wong AJ, Beachy PA (2011) Hedgehog -responsive candidate cell of origin for diffuse intrinsic pontine glioma

  14. The transcription factor Olig2 is important for the biology of diffuse intrinsic pontine gliomas.

    Science.gov (United States)

    Anderson, Jane L; Muraleedharan, Ranjithmenon; Oatman, Nicole; Klotter, Amanda; Sengupta, Satarupa; Waclaw, Ronald R; Wu, Jianqiang; Drissi, Rachid; Miles, Lili; Raabe, Eric H; Weirauch, Matthew L; Fouladi, Maryam; Chow, Lionel M; Hoffman, Lindsey; DeWire, Mariko; Dasgupta, Biplab

    2017-08-01

    Diffuse intrinsic pontine glioma (DIPG) is a high-grade brainstem glioma of children with dismal prognosis. There is no single unifying model about the cell of origin of DIPGs. Proliferating cells in the developing human and mouse pons, the site of DIPGs, express neural stem/progenitor cell (NPC) markers, including Sox2, nestin, vimentin, Olig2, and glial fibrillary acidic protein, in an overlapping and non-overlapping manner, suggesting progenitor cell heterogeneity in the pons. It is thought that during a restricted window of postnatal pons development, a differentiation block caused by genetic/epigenetic changes leads to unrestrained progenitor proliferation and DIPG development. Nearly 80% of DIPGs harbor a mutation in the H3F3A or the related HIST1H3B gene. Supporting the impaired differentiation model, NPCs derived from human induced pluripotent stem cells expressing the H3F3A mutation showed complete differentiation block. However, the mechanisms regulating an altered differentiation program in DIPG are unknown. We established syngeneic serum-dependent and independent primary DIPG lines, performed molecular characterization of DIPG lines in vitro and in an orthotopic xenograft model, and used small hairpin RNA to examine Olig2 function in DIPG. The transcription factor Olig2 is highly expressed in 70%-80% of DIPGs. Here we report that Olig2 expression and DIPG differentiation are mutually exclusive events in vitro, and only DIPG cells that retained Olig2 in vitro formed robust Olig2-positive brainstem glioma with 100% penetrance in a xenograft model. Our results indicate Olig2 as an onco-requisite factor in DIPG and propose investigation of Olig2 target genes as novel candidates in DIPG therapy. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  15. Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries.

    Directory of Open Access Journals (Sweden)

    Sonya Hui

    Full Text Available We recently identified sphingosine-1-phosphate (S1P signaling and the cystic fibrosis transmembrane conductance regulator (CFTR as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i express critical S1P signaling elements, (ii constrict in response to S1P and (iii lose myogenic responsiveness following S1P receptor antagonism (JTE013. However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.

  16. Moderate restriction of macrophage-tropic human immunodeficiency virus type 1 by SAMHD1 in monocyte-derived macrophages.

    Science.gov (United States)

    Taya, Kahoru; Nakayama, Emi E; Shioda, Tatsuo

    2014-01-01

    Macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains are able to grow to high titers in human monocyte-derived macrophages. However, it was recently reported that cellular protein SAMHD1 restricts HIV-1 replication in human cells of the myeloid lineage, including monocyte-derived macrophages. Here we show that degradation of SAMHD1 in monocyte-derived macrophages was associated with moderately enhanced growth of the macrophage-tropic HIV-1 strain. SAMHD1 degradation was induced by treating target macrophages with vesicular stomatitis virus glycoprotein-pseudotyped human immunodeficiency virus type 2 (HIV-2) particles containing viral protein X. For undifferentiated monocytes, HIV-2 particle treatment allowed undifferentiated monocytes to be fully permissive for productive infection by the macrophage-tropic HIV-1 strain. In contrast, untreated monocytes were totally resistant to HIV-1 replication. These results indicated that SAMHD1 moderately restricts even a macrophage-tropic HIV-1 strain in monocyte-derived macrophages, whereas the protein potently restricts HIV-1 replication in undifferentiated monocytes.

  17. Exercise increases TBC1D1 phosphorylation in human skeletal muscle

    Science.gov (United States)

    Jessen, Niels; An, Ding; Lihn, Aina S.; Nygren, Jonas; Hirshman, Michael F.; Thorell, Anders

    2011-01-01

    Exercise and weight loss are cornerstones in the treatment and prevention of type 2 diabetes, and both interventions function to increase insulin sensitivity and glucose uptake into skeletal muscle. Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1. Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation. In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood. In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle. Ten obese (BMI 33.4 ± 2.4, M-value 4.3 ± 0.5) subjects were studied at baseline and after a 2-wk dietary intervention. Muscle biopsies were obtained from the subjects in the resting (basal) state and immediately following a 30-min exercise bout (70% V̇o2 max). Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser711 (AMPK), TBC1D1 Ser231 (AMPK), TBC1D1 Ser660 (AMPK), TBC1D1 Ser700 (AMPK), and TBC1D1 Thr590 (Akt). The diet intervention that consisted of a major shift in the macronutrient composition resulted in a 4.2 ± 0.4 kg weight loss (P < 0.001) and a significant increase in insulin sensitivity (M value 5.6 ± 0.6), but surprisingly, there was no effect on expression or phosphorylation of any of the muscle-signaling proteins. Exercise increased muscle AMPKα2 activity but did not increase Akt phosphorylation. Exercise increased phosphorylation on AS160 Ser711, TBC1D1 Ser231, and TBC1D1 Ser660 but had no effect on TBC1D1 Ser700. Exercise did not increase TBC1D1 Thr590 phosphorylation or TBC1D1/AS160 PAS

  18. Análisis traceológico de la cerámica: modelado y espacio social durante el postalayótico (V-I A.C.) en la Península de Santa Ponça (Calvià, Mallorca)

    OpenAIRE

    Garcia Rosselló, Jaume

    2010-01-01

    La tesis doctoral que presentamos a continuación bajo el título: “Análisis traceológico de la cerámica: modelado y espacio social durante el postalayótico (V-I A.C.) en la Península de Santa Ponça (Calvià, Mallorca) tiene una doble orientación: Por una parte es una nueva propuesta metodológica fundamentada en la reconstrucción de los sistemas de modelado por medio de la traceología cerámica. Por otro, es una aplicación metodológica sobre un conjunto de cerámicas adscritas a la edad de hierro ...

  19. mTORC1 directly phosphorylates and regulates human MAF1.

    OpenAIRE

    Michels Annemieke A; Robitaille Aaron M; Buczynski-Ruchonnet Diane; Hodroj Wassim; Reina Jaime H; Hall Michael N; Hernandez Nouria

    2010-01-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the p...

  20. Action of a diffusible target-derived chemoattractant on cortical axon branch induction and directed growth.

    Science.gov (United States)

    Sato, M; Lopez-Mascaraque, L; Heffner, C D; O'Leary, D D

    1994-10-01

    Cortical axons innervate their brainstem target, the basilar pons, by the initiation and extension of collateral branches interstitially along their length. To address whether a diffusible pons-derived chemoattractant controls these events, we used cocultures in collagen matrices and time-lapse microscopy. Pontine explants enhanced by 5-fold the de novo initiation of transient branches along cortical axons; most branches were directed toward pons. Of the branches extended toward pons, 2%-3% were stabilized; those extended away were not. Pontine explants also enhanced the stable bifurcation of growth cones and prompted directional changes by growth cone turning and collateral extension. These effects were distance dependent and mimicked by pons-conditioned medium. This evidence indicates that the pons activity promotes branch initiation interstitially along cortical axons, a novel property for a chemoattractant, and provides a directional cue for their growth. These findings suggest that the pons chemoattractant serves as a diffusible target-recognition molecule.