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Sample records for leho kiv simmo

  1. Basic principles of the KIV model and its application to the navigation problem.

    PubMed

    Kozma, Robert; Freeman, Walter J

    2003-06-01

    EEG measurements indicate the presence of common-mode, coherent oscillations shared by multiple cortical areas. In previous studies the KIII model has been introduced, which interprets the experimental observations as nonlinear, spatially distributed dynamical oscillations of locally coupled neural populations. KIII can account for the fast and robust classification and pattern recognition in sensory cortices. In order to describe selection of action, planning, and spatial orientation functions, in this paper we expand KIII into the KIV model. KIV approximates the operation of the corticostriatal-hippocampal system. KIV consists of three KI, eight KII and three KIII components, including sensory and cortical systems, as well as the hippocampus, amygdala, and the septum. KIV implements various types of dynamic neural activities. The neural activity patterns determine the emergence of global spatial encoding to implement the orientation function of a simulated animal. Our results indicate the mechanisms, which we believe support the generation of cognitive maps in the hippocampus based on the sensory input-based destabilization of cortical spatio-temporal patterns. In this paper, we describe the conceptual design of the KIV model. We outline the biological background and motivation of the basic principles that are applied to design the KIV computational model. We use the KIV model to explain how the hippocampal neural circuitry functions are constructed and controlled by the corticostriatal-hippocampal loops, supplemented with specific subcortical units. In the second part, we implement these principles using the example of the hippocampal formation as a KIII unit. We demonstrate the learning and navigation principles using the Evolving Multi-module Mobile Agent (EMMA) in 2D software environment. PMID:15011280

  2. Sequence variation within the KIV-2 copy number polymorphism of the human LPA gene in African, Asian, and European populations.

    PubMed

    Noureen, Asma; Fresser, Friedrich; Utermann, Gerd; Schmidt, Konrad

    2015-01-01

    Amazingly little sequence variation is reported for the kringle IV 2 copy number variation (KIV 2 CNV) in the human LPA gene. Apart from whole genome sequencing projects, this region has only been analyzed in some detail in samples of European populations. We have performed a systematic resequencing study of the exonic and flanking intron regions within the KIV 2 CNV in 90 alleles from Asian, European, and four different African populations. Alleles have been separated according to their CNV length by pulsed field gel electrophoresis prior to unbiased specific PCR amplification of the target regions. These amplicons covered all KIV 2 copies of an individual allele simultaneously. In addition, cloned amplicons from genomic DNA of an African individual were sequenced. Our data suggest that sequence variation in this genomic region may be higher than previously appreciated. Detection probability of variants appeared to depend on the KIV 2 copy number of the analyzed DNA and on the proportion of copies carrying the variant. Asians had a high frequency of so-called KIV 2 type B and type C (together 70% of alleles), which differ by three or two synonymous substitutions respectively from the reference type A. This is most likely explained by the strong bottleneck suggested to have occurred when modern humans migrated to East Asia. A higher frequency of variable sites was detected in the Africans. In particular, two previously unreported splice site variants were found. One was associated with non-detectable Lp(a). The other was observed at high population frequencies (10% to 40%). Like the KIV 2 type B and C variants, this latter variant was also found in a high proportion of KIV 2 repeats in the affected alleles and in alleles differing in copy numbers. Our findings may have implications for the interpretation of SNP analyses in other repetitive loci of the human genome.

  3. Effects on hypothalamus when CPG is fed back to basal ganglia based on KIV model.

    PubMed

    Lu, Qiang; Li, Wenfeng; Tian, Juan; Zhang, Xixue

    2015-02-01

    The KIV model approximates the operation of the basic vertebrate forebrain together with the basal ganglia and motor systems. In KIV model, the hypothalamus and the basal ganglia which are two important parts in the midline forebrain are closely associated with the locomotion. The CPG model with time delay is established in this paper and the stability of this CPG model is discussed. The CPG output is treated as the proprioception and fed back to the basal ganglia. We focus on the effects on the hypothalamus and the basal ganglia when the time delay parameter a d , the CPG amplitude parameter e and the CPG frequency parameter T r are changed. Through analysis, we find that there exists optimum value of the parameters a d or T r which can make the synchronization of the hypothalamus optimum when the CPG is added into the basal ganglia. The results could have important implications for biological processes which are about interaction between the neural network and the CPG.

  4. Apolipoprotein(a) Kringle-IV Type 2 Copy Number Variation Is Associated with Venous Thromboembolism

    PubMed Central

    Sticchi, Elena; Magi, Alberto; Kamstrup, Pia R.; Marcucci, Rossella; Prisco, Domenico; Martinelli, Ida; Mannucci, Pier Mannuccio; Abbate, Rosanna; Giusti, Betti

    2016-01-01

    In addition to the established association between high lipoprotein(a) [Lp(a)] concentrations and coronary artery disease, an association between Lp(a) and venous thromboembolism (VTE) has also been described. Lp(a) is controlled by genetic variants in LPA gene, coding for apolipoprotein(a), including the kringle-IV type 2 (KIV-2) size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs) (rs1853021, rs1800769, rs3798220, rs10455872) in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range) 11(6–17) vs 15(9–25), p<0.0001]. A significantly higher prevalence of KIV-2 repeat number ≤7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001). KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9), as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women. PMID:26900838

  5. Regulation of mitogen-activated protein kinases by a calcium/calmodulin-dependent protein kinase cascade.

    PubMed Central

    Enslen, H; Tokumitsu, H; Stork, P J; Davis, R J; Soderling, T R

    1996-01-01

    Membrane depolarization of NG108 cells gives rapid (< 5 min) activation of Ca2+/calmodulin-dependent protein kinase IV (CaM-KIV), as well as activation of c-Jun N-terminal kinase (JNK). To investigate whether the Ca2+-dependent activation of mitogen-activated protein kinases (ERK, JNK, and p38) might be mediated by the CaM kinase cascade, we have transfected PC12 cells, which lack CaM-KIV, with constitutively active mutants of CaM kinase kinase and/or CaM-KIV (CaM-KKc and CaM-KIVc, respectively). In the absence of depolarization, CaM-KKc transfection had no effect on Elk-dependent transcription of a luciferase reporter gene, whereas CaM-KIVc alone or in combination with CaM-KKc gave 7- to 10-fold and 60- to 80-fold stimulations, respectively, which were blocked by mitogen-activated protein (MAP) kinase phosphatase cotransfection. When epitope-tagged constructs of MAP kinases were co-transfected with CaM-KKc plus CaM-KIVc, the immunoprecipitated MAP kinases were activated 2-fold (ERK-2) and 7- to 10-fold (JNK-1 and p38). The JNK and p38 pathways were further investigated using specific c-Jun or ATF2-dependent transcriptional assays. We found that c-Jun/ATF2-dependent transcriptions were enhanced 7- to 10-fold by CaM-KIVc and 20- to 30-fold by CaM-KKc plus CaM-KIVc. In the case of the Jun-dependent transcription, this effect was not due to direct phosphorylation of c-Jun by activated CaM-KIV, since transcription was blocked by a dominant-negative JNK and by two MAP kinase phosphatases. Mutation of the phosphorylation site (Thr196) in CaM-KIV, which mediates its activation by CaM-KIV kinase, prevented activation of Elk-1, c-Jun, and ATF2 by the CaM kinase cascade. These results establish a new Ca2+-dependent mechanism for regulating MAP kinase pathways and resultant transcription. Images Fig. 1 Fig. 3 Fig. 4 PMID:8855261

  6. Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV.

    PubMed

    Jha, S; Dong, B E; Xue, Y; Delotterie, D F; Vail, M G; Sakata, K

    2016-01-01

    Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0-2 months), young adult (2-4 months), and old adult (12-14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults. PMID:27648918

  7. Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a).

    PubMed

    Leibundgut, Gregor; Scipione, Corey; Yin, Huiyong; Schneider, Matthias; Boffa, Michael B; Green, Simone; Yang, Xiaohong; Dennis, Edward; Witztum, Joseph L; Koschinsky, Marlys L; Tsimikas, Sotirios

    2013-10-01

    Oxidized phospholipids (OxPLs) are present on apolipoprotein (a) [apo(a)] and lipoprotein (a) [Lp(a)] but the determinants influencing their binding are not known. The presence of OxPLs on apo(a)/Lp(a) was evaluated in plasma from healthy humans, apes, monkeys, apo(a)/Lp(a) transgenic mice, lysine binding site (LBS) mutant apo(a)/Lp(a) mice with Asp(55/57)→Ala(55/57) substitution of kringle (K)IV10)], and a variety of recombinant apo(a) [r-apo(a)] constructs. Using antibody E06, which binds the phosphocholine (PC) headgroup of OxPLs, Western and ELISA formats revealed that OxPLs were only present in apo(a) with an intact KIV10 LBS. Lipid extracts of purified human Lp(a) contained both E06- and nonE06-detectable OxPLs by tandem liquid chromatography-mass spectrometry (LC-MS/MS). Trypsin digestion of 17K r-apo(a) showed PC-containing OxPLs covalently bound to apo(a) fragments by LC-MS/MS that could be saponified by ammonium hydroxide. Interestingly, PC-containing OxPLs were also present in 17K r-apo(a) with Asp(57)→Ala(57) substitution in KIV10 that lacked E06 immunoreactivity. In conclusion, E06- and nonE06-detectable OxPLs are present in the lipid phase of Lp(a) and covalently bound to apo(a). E06 immunoreactivity, reflecting pro-inflammatory OxPLs accessible to the immune system, is strongly influenced by KIV10 LBS and is unique to human apo(a), which may explain Lp(a)'s pro-atherogenic potential. PMID:23828779

  8. Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV.

    PubMed

    Jha, S; Dong, B E; Xue, Y; Delotterie, D F; Vail, M G; Sakata, K

    2016-09-20

    Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0-2 months), young adult (2-4 months), and old adult (12-14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults.

  9. Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV

    PubMed Central

    Jha, S; Dong, B E; Xue, Y; Delotterie, D F; Vail, M G; Sakata, K

    2016-01-01

    Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0–2 months), young adult (2–4 months), and old adult (12–14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults. PMID:27648918

  10. Role of mitochondrial transamination in branched chain amino acid metabolism

    SciTech Connect

    Hutson, S.M.; Fenstermacher, D.; Mahar, C.

    1988-03-15

    Oxidative decarboxylation and transamination of 1-/sup 14/C-branched chain amino and alpha-keto acids were examined in mitochondria isolated from rat heart. Transamination was inhibited by aminooxyacetate, but not by L-cycloserine. At equimolar concentrations of alpha-ketoiso(1-/sup 14/C)valerate (KIV) and isoleucine, transamination was increased by disrupting the mitochondria with detergent which suggests transport may be one factor affecting the rate of transamination. Next, the subcellular distribution of the aminotransferase(s) was determined. Branched chain aminotransferase activity was measured using two concentrations of isoleucine as amino donor and (1-/sup 14/C)KIV as amino acceptor. The data show that branched chain aminotransferase activity is located exclusively in the mitochondria in rat heart. Metabolism of extramitochondrial branched chain alpha-keto acids was examined using 20 microM (1-/sup 14/C)KIV and alpha-ketoiso(1-/sup 14/C)caproate (KIC). There was rapid uptake and oxidation of labeled branched chain alpha-keto acid, and, regardless of the experimental condition, greater than 90% of the labeled keto acid substrate was metabolized during the 20-min incubation. When a branched chain amino acid (200 microM) or glutamate (5 mM) was present, 30-40% of the labeled keto acid was transaminated while the remainder was oxidized. Provision of an alternate amino acceptor in the form of alpha-keto-glutarate (0.5 mM) decreased transamination of the labeled KIV or KIC and increased oxidation. Metabolism of intramitochondrially generated branched chain alpha-keto acids was studied using (1-/sup 14/C)leucine and (1-/sup 14/C)valine. Essentially all of the labeled branched chain alpha-keto acid produced by transamination of (1-/sup 14/C)leucine or (1-/sup 14/C)valine with a low concentration of unlabeled branched chain alpha-keto acid (20 microM) was oxidized.

  11. Regulation of valine and. alpha. -ketoisocaproate metabolism in rat kidney mitochondria

    SciTech Connect

    Miller, R.H.; Harper, A.E. )

    1988-10-01

    Activities of branched-chain amino acid (BCAA) aminotransferase (BCAT) and {alpha}-keto acid dehydrogenase (BCKD) were assayed in mitochondria isolated from kidneys of rats. Rates of transamination of valine and oxidation of keto acids {alpha}-ketoisocaproate (KIC) or {alpha}-ketoisovalerate (KIV) were estimated using radioactive tracers of the appropriate substrate from amounts of {sup 14}C-labeled products formed. Because of the high mitochondrial BCAT activity, an amino acceptor for BCAT, {alpha}-ketoglutarate ({alpha}-KG) or KIC, was added to the assay medium when valine was the substrate. Rates of valine transamination and subsequent oxidation of the KIV formed were determined with 0.5 mM {alpha}-KG as the amino acceptor; these rates were 5- to 50-fold those without added {alpha}-KG. Rates of CO{sub 2} evolution from valine also increased when KIC was present; however, with KIC concentrations above 0.2 mM, rates of CO{sub 2} evolution from valine declined although rates of transamination continued to rise. When 0.05 mM KIC was added to the assay medium, oxidation of KIC was suppressed by inclusion of valine or glutamate in the medium. When valine was present KIC was not oxidized preferentially, presumably because it was also serving as an amino acceptor for BCAT. These results indicate that as the supply of amino acceptor, {alpha}-KG or KIC, is increased in mitochondria not only is the rate of valine transamination stimulated but also the rate of oxidation of the KIV formed from valine. Thus the rate of oxidation of BCAA can be controlled by factors that influence the rate and direction of BCAA transamination and, thereby, the supply of substrate for BCKD.

  12. Non-Suicidal Self-Injury and Interpersonal Violence in Suicide Attempters.

    PubMed

    Sahlin, Hanna; Moberg, Tomas; Hirvikoski, Tatja; Jokinen, Jussi

    2015-01-01

    The current study compared characteristics of suicidal behavior and interpersonal violence in suicide attempters with and without a history of non-suicidal self-injury (NSSI). A total of 100 suicide attempters were assessed with Karolinska Interpersonal Violence Scale (KIVS) and Karolinska Suicide History Interview concerning interpersonal violence and NSSI. There was a high degree of comorbid NSSI in suicide attempters (44%). Suicide attempters with NSSI-history reported more interpersonal violence as adults and more severe suicidal behavior compared to suicide attempters without NSSI. Comorbid NSSI was related to severity of suicidal behavior in a gender specific manner. Comorbid NSSI in suicide attempters may increase suicide and violence risk.

  13. (1)H NMR-based metabolomic approach for understanding the fermentation behaviors of wine yeast strains.

    PubMed

    Son, Hong-Seok; Hwang, Geum-Sook; Kim, Ki Myong; Kim, Eun-Young; van den Berg, Frans; Park, Won-Mok; Lee, Cherl-Ho; Hong, Young-Shick

    2009-02-01

    (1)H NMR spectroscopy coupled with multivariate statistical analysis was used for the first time to investigate metabolic changes in musts during alcoholic fermentation and wines during aging. Three Saccharomyces cerevisiae yeast strains (RC-212, KIV-1116, and KUBY-501) were also evaluated for their impacts on the metabolic changes in must and wine. Pattern recognition (PR) methods, including PCA, PLS-DA, and OPLS-DA scores plots, showed clear differences for metabolites among musts or wines for each fermentation stage up to 6 months. Metabolites responsible for the differentiation were identified as valine, 2,3-butanediol (2,3-BD), pyruvate, succinate, proline, citrate, glycerol, malate, tartarate, glucose, N-methylnicotinic acid (NMNA), and polyphenol compounds. PCA scores plots showed continuous movements away from days 1 to 8 in all musts for all yeast strains, indicating continuous and active fermentation. During alcoholic fermentation, the highest levels of 2,3-BD, succinate, and glycerol were found in musts with the KIV-1116 strain, which showed the fastest fermentation or highest fermentative activity of the three strains, whereas the KUBY-501 strain showed the slowest fermentative activity. This study highlights the applicability of NMR-based metabolomics for monitoring wine fermentation and evaluating the fermentative characteristics of yeast strains.

  14. Thyroid hormones and adult interpersonal violence among women with borderline personality disorder.

    PubMed

    Sinai, Cave; Hirvikoski, Tatja; Nordström, Anna-Lena; Nordström, Peter; Nilsonne, Åsa; Wilczek, Alexander; Åsberg, Marie; Jokinen, Jussi

    2015-06-30

    Elevated T3 levels have been reported in men with antisocial behavior. The aim of the present study was to investigate the relationship between thyroid hormones and expressed adult interpersonal violence in female patients with borderline personality disorder (BPD). Furthermore, expressed adult interpersonal violence in female BPD patients was compared to healthy female controls. A total of 92 clinically euthyroid women with BPD and 57 healthy women were assessed with the Karolinska Interpersonal Violence Scales (KIVS). Baseline thyroid function was evaluated by measuring plasma free and bound triiodothyronine (FT3 and T3), thyroxine (FT4 and T4), and thyroid-stimulating hormone (TSH) with immunoassays in patients. Plasma cortisol was also measured. Among females with BPD, expressed interpersonal violence as an adult showed a significant positive correlation with the T3 levels. The mean expression of interpersonal violence as an adult was significantly higher in BPD patients as compared to healthy controls. The multiple regression model indicated that two independent predictors of KIVS expressed interpersonal violence as an adult: T3 and comorbid diagnosis of alcohol abuse. Association between T3 levels and violent/aggressive behavior earlier reported exclusively in male samples may be valid also in females with BPD.

  15. The characterization for the binding of calcium and terbium to Euplotes octocarinatus centrin

    NASA Astrophysics Data System (ADS)

    Yaqin, Zhao; Jiuying, Feng; Aihua, Liang; Binsheng, Yang

    2009-01-01

    Centrin is a member of the EF-hand superfamily that plays critical role in the centrosome duplication and separation. In the present paper, we characterized properties of metal ions binding to Euplotes octocarinatus centrin (EoCen) by fluorescence spectra and circular dichroism (CD) spectra. Changes of fluorescence spectra and α-helix contents of EoCen proved that Tb 3+ and Ca 2+ induced great conformational changes of EoCen resulting in exposing hydrophobic surfaces. At pH 7.4, Ca 2+ (and Tb 3+) bond with EoCen at the ratio of 4:1. Equilibrium experiment indicated that Ca 2+ and Tb 3+ exhibited different binding capabilities for C- and N-terminal domains of protein. C-terminal domain bond with Ca 2+ or Tb 3+ ˜ 100-fold more strongly than N-terminal. Aromatic residue-sensitized Tb 3+ energy transfer suggested that site IV bond to Tb 3+ or Ca 2+ more strongly than site III. Based on fluorescence titration curves, we reckoned the conditional binding constants of EoCen site IV quantitatively to be KIV = (1.23 ± 0.51) × 10 8 M -1 and KIV = (6.82 ± 0.33) × 10 5 M -1 with Tb 3+ and Ca 2+, respectively. Metal ions bond to EoCen in the order of IV > III > II, I.

  16. Evidence for several independent genetic variants affecting lipoprotein (a) cholesterol levels

    PubMed Central

    Lu, Wensheng; Cheng, Yu-Ching; Chen, Keping; Wang, Hong; Gerhard, Glenn S.; Still, Christopher D.; Chu, Xin; Yang, Rongze; Parihar, Ankita; O'Connell, Jeffrey R.; Pollin, Toni I.; Angles-Cano, Eduardo; Quon, Michael J.; Mitchell, Braxton D.; Shuldiner, Alan R.; Fu, Mao

    2015-01-01

    Lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerosis-related events that is under strong genetic control (heritability = 0.68–0.98). However, causal mutations and functional validation of biological pathways modulating Lp(a) metabolism are lacking. We performed a genome-wide association scan to identify genetic variants associated with Lp(a)-cholesterol levels in the Old Order Amish. We confirmed a previously known locus on chromosome 6q25-26 and found Lp(a) levels also to be significantly associated with a SNP near the APOA5–APOA4–APOC3–APOA1 gene cluster on chromosome 11q23 linked in the Amish to the APOC3 R19X null mutation. On 6q locus, we detected associations of Lp(a)-cholesterol with 118 common variants (P = 5 × 10−8 to 3.91 × 10−19) spanning a ∼5.3 Mb region that included the LPA gene. To further elucidate variation within LPA, we sequenced LPA and identified two variants most strongly associated with Lp(a)-cholesterol, rs3798220 (P = 1.07 × 10−14) and rs10455872 (P = 1.85 × 10−12). We also measured copy numbers of kringle IV-2 (KIV-2) in LPA using qPCR. KIV-2 numbers were significantly associated with Lp(a)-cholesterol (P = 2.28 × 10−9). Conditional analyses revealed that rs3798220 and rs10455872 were associated with Lp(a)-cholesterol levels independent of each other and KIV-2 copy number. Furthermore, we determined for the first time that levels of LPA mRNA were higher in the carriers than non-carriers of rs10455872 (P = 0.0001) and were not different between carriers and non-carriers of rs3798220. Protein levels of apo(a) were higher in the carriers than non-carriers of both rs10455872 and rs3798220. In summary, we identified multiple independent genetic determinants for Lp(a)-cholesterol. These findings provide new insights into Lp(a) regulation. PMID:25575512

  17. Combining Task Execution and Background Knowledge for the Verification of Medical Guidelines

    NASA Astrophysics Data System (ADS)

    Hommersom, Arjen; Groot, Perry; Lucas, Peter; Balser, Michael; Schmitt, Jonathan

    The use of a medical guideline can be seen as the execution of computational tasks, sequentially or in parallel, in the face of patient data. It has been shown that many of such guidelines can be represented as a 'network of tasks', i.e., as a number of steps that have a specific function or goal. To investigate the quality of such guidelines we propose a formalization of criteria for good practice medicine a guideline should comply to. We use this theory in conjunction with medical background knowledge to verify the quality of a guideline dealing with diabetes mellitus type 2 using the interactive theorem prover KIV. Verification using task execution and background knowledge is a novel approach to quality checking of medical guidelines.

  18. The 16th Werner Brandt Workshop on charged particle penetration phenomena

    SciTech Connect

    1996-05-01

    This report contains viewgraphs on the following topics: impact parameter dependence of charge transfer and energy loss; nonlinear dynamical response of the electron gas: comparison of some simple theories; stopping of ultrarelativistic ions in solids (33.2-TeV {sup 108}Pb); collective excitation in reduced dimensionality; collective states in atoms and cluster; plasmon coupling with external probes; atomic collisions with antiprotons; layer-number scaling in ultra-thin film stopping and energetics; atom-surface scattering under classical conditions; nonlinear effect of sweeping-out electrons in stopping power and electron emission in cluster impacts; electron emission from fast grazing collisions of ions with silicon surfaces; electron emission from ultra-thin carbon foils by kiV ions; Auger rates for highly charged ions in metals; Auger and plasmon assisted neutralization at surfaces; low energy (< 5eV) F{sup +} and F{sup -} ions transmission through condensed layers of water: enhancement and attenuation processes; charge transfer for H interacting with Al: atomic levels and linewidths; scattered projectile angular and charge state distributions for grazing collisions of multicharged ions with metal and insulator single crystal targets; the prolate hyperboloidat model in scanning probe microscopy; scanning probe microscopy of large biomolecules; microcantilever sensors; solution of the Fokker-Planck equation for electron transport using analytic spatial moments; and effective charge parametrization for z = 3-17 projectiles in composite targets.

  19. Radio Astrometry of the Triple Systems Algol and UX Arietis

    NASA Astrophysics Data System (ADS)

    Peterson, W. M.; Mutel, R. L.; Lestrade, J.-F.; Güdel, M.; Goss, W. M.

    2011-08-01

    We have used multi-epoch long-baseline radio interferometry to determine the proper motion and orbital elements of Algol and UX Arietis, two radio-bright, close binary stellar systems with distant tertiary components. For Algol, we refine the proper motion and outer orbit solutions, confirming the recent result of Zavala et al. that the inner orbit is retrograde. The radio centroid closely tracks the motion of the KIV secondary. In addition, the radio morphology varies from double-lobed at low flux level to crescent-shaped during active periods. These results are most easily interpreted as synchrotron emission from a large, co-rotating meridional loop centered on the K star. If this is correct, it provides a radio-optical frame tie candidate with an uncertainty ±0.5 mas. For UX Arietis, we find an outer orbit solution that accounts for previous very long baseline interferometry observations of an acceleration term in the proper motion fit. The outer orbit solution is also consistent with previously published radial velocity curves and speckle observations of a third body. The derived tertiary mass, 0.75 solar masses, is consistent with the K1 main-sequence star detected spectroscopically. The inner orbit solution favors radio emission from the active K0IV primary only. The radio morphology, consisting of a single, partially resolved emission region, may be associated with the persistent polar spot observed using Doppler imaging.

  20. Cinnamic acid amides from Tribulus terrestris displaying uncompetitive α-glucosidase inhibition.

    PubMed

    Song, Yeong Hun; Kim, Dae Wook; Curtis-Long, Marcus J; Park, Chanin; Son, Minky; Kim, Jeong Yoon; Yuk, Heung Joo; Lee, Keun Woo; Park, Ki Hun

    2016-05-23

    The α-glucosidase inhibitory potential of Tribulus terrestris extracts has been reported but as yet the active ingredients are unknown. This study attempted to isolate the responsible metabolites and elucidate their inhibition mechanism of α-glucosidase. By fractionating T. terristris extracts, three cinnamic acid amide derivatives (1-3) were ascertained to be active components against α-glucosidase. The lead structure, N-trans-coumaroyltyramine 1, showed significant inhibition of α-glucosidase (IC50 = 0.42 μM). Moreover, all active compounds displayed uncompetitive inhibition mechanisms that have rarely been reported for α-glucosidase inhibitors. This kinetic behavior was fully demonstrated by showing a decrease of both Km and Vmax, and Kik/Kiv ratio ranging between 1.029 and 1.053. We progressed to study how chemical modifications to the lead structure 1 may impact inhibition. An α, β-unsaturation carbonyl group and hydroxyl group in A-ring of cinnamic acid amide emerged to be critical functionalities for α-glucosidase inhibition. The molecular modeling study revealed that the inhibitory activities are tightly related to π-π interaction as well as hydrogen bond interaction between enzyme and inhibitors.

  1. Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients

    PubMed Central

    Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya

    2016-01-01

    Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide. PMID:26784730

  2. Isobutanol production from an engineered Shewanella oneidensis MR-1.

    PubMed

    Jeon, Jong-Min; Park, Hyojung; Seo, Hyung-Min; Kim, Jung-Ho; Bhatia, Shashi Kant; Sathiyanarayanan, Ganesan; Song, Hun-Suk; Park, Sung-Hee; Choi, Kwon-Young; Sang, Byoung-In; Yang, Yung-Hun

    2015-11-01

    Shewanella oneidensis MR-1 is one of the most well-known metal-reducing bacteria and it has been extensively studied for microbial fuel cell and bioremediation aspects. In this study, we have examined S. oneidensis MR-1 as an isobutanol-producing host by assessing three key factors such as isobutanol synthetic genes, carbon sources, and electron supply systems. Heterologous Ehrlich pathway genes, kivD encoding ketoisovalerate decarboxylase and adh encoding alcohol dehydrogenase, were constructed in S. oneidensis MR-1. Among the composition of carbon sources examined, 2% of N-acetylglucosamine, 1.5% of pyruvate and 2% of lactate were found to be the most optimal nutrients and resulted in 10.3 mg/L of isobutanol production with 48 h of microaerobic incubation. Finally, the effects of metal ions (electron acceptor) and direct electron transfer systems on isobutanol production were investigated, and Fe(2+) ions increased the isobutanol production up to 35%. Interestingly, deletion of mtrA and mtrB, genes responsible for membrane transport systems, did not have significant impact on isobutanol production. Finally, we applied engineered S. oneidensis to a bioelectrical reactor system to investigate the effect of a direct electron supply system on isobutanol production, and it resulted in an increased growth and isobutanol production (up to 19.3 mg/L). This report showed the feasibility of S. oneidensis MR-1 as a genetic host to produce valuable biochemicals and combine an electron-supplying system with biotechnological applications.

  3. A large coronal loop in the Algol system.

    PubMed

    Peterson, W M; Mutel, R L; Güdel, M; Goss, W M

    2010-01-14

    The close binary Algol system contains a radio-bright KIV subgiant star in a very close (0.062 astronomical units) and rapid (2.86 day) orbit with a main sequence B8 star. Because the rotation periods of the two stars are tidally locked to the orbital period, the rapid rotation drives a magnetic dynamo. A large body of evidence points to the existence of an extended, complex coronal magnetosphere originating at the cooler K subgiant. The detailed morphology of the subgiant's corona and its possible interaction with its companion are unknown, though theory predicts that the coronal plasma should be confined in a magnetic loop structure, as seen on the Sun. Here we report multi-epoch radio imaging of the Algol system, in which we see a large, persistent coronal loop approximately one subgiant diameter in height, whose base is straddling the subgiant and whose apex is oriented towards the B8 star. This suggests that a persistent asymmetric magnetic field structure is aligned between the two stars. The loop is larger than anticipated theoretically, but the size may be the result of a magnetic interaction between the two stars. PMID:20075916

  4. RADIO ASTROMETRY OF THE TRIPLE SYSTEMS ALGOL AND UX ARIETIS

    SciTech Connect

    Peterson, W. M.; Mutel, R. L.; Lestrade, J.-F.; Guedel, M.; Goss, W. M.

    2011-08-20

    We have used multi-epoch long-baseline radio interferometry to determine the proper motion and orbital elements of Algol and UX Arietis, two radio-bright, close binary stellar systems with distant tertiary components. For Algol, we refine the proper motion and outer orbit solutions, confirming the recent result of Zavala et al. that the inner orbit is retrograde. The radio centroid closely tracks the motion of the KIV secondary. In addition, the radio morphology varies from double-lobed at low flux level to crescent-shaped during active periods. These results are most easily interpreted as synchrotron emission from a large, co-rotating meridional loop centered on the K star. If this is correct, it provides a radio-optical frame tie candidate with an uncertainty {+-}0.5 mas. For UX Arietis, we find an outer orbit solution that accounts for previous very long baseline interferometry observations of an acceleration term in the proper motion fit. The outer orbit solution is also consistent with previously published radial velocity curves and speckle observations of a third body. The derived tertiary mass, 0.75 solar masses, is consistent with the K1 main-sequence star detected spectroscopically. The inner orbit solution favors radio emission from the active K0IV primary only. The radio morphology, consisting of a single, partially resolved emission region, may be associated with the persistent polar spot observed using Doppler imaging.

  5. Isobutanol production from an engineered Shewanella oneidensis MR-1.

    PubMed

    Jeon, Jong-Min; Park, Hyojung; Seo, Hyung-Min; Kim, Jung-Ho; Bhatia, Shashi Kant; Sathiyanarayanan, Ganesan; Song, Hun-Suk; Park, Sung-Hee; Choi, Kwon-Young; Sang, Byoung-In; Yang, Yung-Hun

    2015-11-01

    Shewanella oneidensis MR-1 is one of the most well-known metal-reducing bacteria and it has been extensively studied for microbial fuel cell and bioremediation aspects. In this study, we have examined S. oneidensis MR-1 as an isobutanol-producing host by assessing three key factors such as isobutanol synthetic genes, carbon sources, and electron supply systems. Heterologous Ehrlich pathway genes, kivD encoding ketoisovalerate decarboxylase and adh encoding alcohol dehydrogenase, were constructed in S. oneidensis MR-1. Among the composition of carbon sources examined, 2% of N-acetylglucosamine, 1.5% of pyruvate and 2% of lactate were found to be the most optimal nutrients and resulted in 10.3 mg/L of isobutanol production with 48 h of microaerobic incubation. Finally, the effects of metal ions (electron acceptor) and direct electron transfer systems on isobutanol production were investigated, and Fe(2+) ions increased the isobutanol production up to 35%. Interestingly, deletion of mtrA and mtrB, genes responsible for membrane transport systems, did not have significant impact on isobutanol production. Finally, we applied engineered S. oneidensis to a bioelectrical reactor system to investigate the effect of a direct electron supply system on isobutanol production, and it resulted in an increased growth and isobutanol production (up to 19.3 mg/L). This report showed the feasibility of S. oneidensis MR-1 as a genetic host to produce valuable biochemicals and combine an electron-supplying system with biotechnological applications. PMID:26280214

  6. On the evolution of the nova-like variable AE Aquarii

    NASA Astrophysics Data System (ADS)

    Meintjes, P. J.

    2002-10-01

    A possible evolution for the enigmatic cataclysmic variable AE Aquarii is considered that may put into context the long orbital period and short white dwarf rotation period compared with other DQ Her systems. It has been shown that mass transfer could have been initiated when the secondary KIV-V star was already somewhat evolved when it established Roche lobe contact. In this initial phase the orbital period of the system was probably Porb,i~ 8.5 h, and the white dwarf rotation period P*,i > 1 h. Mass transfer in the form of diamagnetic gas blobs will result in an initial discless accretion process, resulting in an efficient drain of the binary orbital angular momentum. Since the initial mass ratio of the binary was probably qi~ 0.8, a high mass transfer rate and a slow expansion of the Roche lobe of the secondary star followed, accompanied by a fast expanding secondary following the mass loss. This could have resulted in the KIV-V secondary flooding its Roche surface, causing a run-away mass transfer of that lasted for approximately , during which time the binary expanded to an orbital period of approximately Porb~ 11 h. During this phase the mass accretion rate on to the surface of the white dwarf most probably exceeded the critical value for stable nuclear burning , which could have resulted in AE Aqr turning into an ultrasoft X-ray source. The high mass transfer terminated when a critical mass ratio of qcrit= 0.73 was reached. Disc torques spun-up the white dwarf to a period close to 33 s within the time-scale before the high mass transfer shut down when qcrit was reached. The decrease in the mass loss of the secondary allowed it to re-establish hydrostatic equilibrium on the dynamical time-scale (fraction of a day). From this point when qcrit is reached the mass transfer and binary evolution proceed at a slower rate since mass transfer from the secondary star is driven by magnetic braking of the secondary on a time-scale , which is the same as the thermal time

  7. Second-order and third-order elastic properties of diamond: An ab initio study

    NASA Astrophysics Data System (ADS)

    Clerc, Daryl G.; Ledbetter, Hassel

    2005-10-01

    Diamond's second-order elastic properties, and several third-order properties associated with uniform deformation, were calculated using ab initio all-electron density-functional theory. The predicted second-order elastic properties and equilibrium lattice parameter, in units of GPa and nm, are c11=1043(5), c12=128(5), c44=534(17), bulk modulus B=433(5), shear modulus G=502(10), Poisson ratio μ=0.082(5), and a=0.35569(2), where the parenthetic number is the uncertainty. The second-order force constants, in units of GPa, are kI=3843(108), kII=2346(17), kIII=2847(35), and kIV=5635(45). Here, subscripts I IV denote four strains whose tensor elements are [ɛ, ɛ, ɛ, 0, 0, 0], [ɛ, ɛ, 0, 0, 0, 0], [ɛ, ɛ, -ɛ, 0, 0, 0], and [ɛ, ɛ, ɛ, ɛ, ɛ, ɛ], respectively, using 6-component notation in the format [ɛ1, ɛ2, ɛ3, ɛ4, ɛ5, ɛ6]. Predicted inelastic properties include the third-order force constant corresponding to uniform dilation gI=-55,000(3,500) GPa, the bulk-modulus pressure derivative ∂B/∂P=4.7(3), and the overall Gruneisen parameter γG=0.85(15). Both our second-order and third-order properties agree well with measured values obtained by ultrasonics and by Raman spectroscopy.

  8. Geophysical imaging of karst features in Missouri

    NASA Astrophysics Data System (ADS)

    Obi, Jeremiah Chukwunonso

    Automated electrical resistivity tomography (ERT) supported with multichannel analysis of surface waves (MASW) and boring data were used to map karst related features in Missouri in order to understand karst processes better in Missouri. Previous works on karst in Missouri were mostly surficial mapping of bedrock outcrops and joints, which are not enough to define the internal structure of karst system, since most critical processes in karst occur underground. To understand these processes better, the density, placement and pattern of karst related features like solution-widened joints and voids, as well as top of bedrock were mapped. In the course of the study, six study sites were visited in Missouri. The sites were in Nixa, Gasconade River Bridge in Lebanon, Battlefield, Aurora, Protem and Richland. The case studies reflect to a large extent some of the problems inherent in karst terrain, ranging from environmental problems to structural problems especially sinkhole collapses. The result of the study showed that karst in Missouri is mostly formed as a result of piping of sediments through solution-widened joints, with a pattern showing that the joints/fractures are mostly filled with moist clay-sized materials of low resistivity values. The highest density of mapped solution-widened joints was one in every one hundred and fifty feet, and these areas are where intense dissolution is taking place, and bedrock pervasively fractured. The study also showed that interpreted solution-widened joints trend in different directions, and often times conform with known structural lineaments in the area. About 40% of sinkhole collapses in the study areas are anthropogenic. Karst in Missouri varies, and can be classified as a combination of kI (juvenile), kIII (mature) and kIV (complex) karsts.

  9. Functional and structural specific roles of activity-driven BDNF within circuits formed by single spiny stellate neurons of the barrel cortex

    PubMed Central

    Sun, Qian-Quan; Zhang, Zhi; Sun, June; Nair, Anand S.; Petrus, Dan P.; Zhang, Chunzhao

    2014-01-01

    Brain derived neurotrophic factor (BDNF) plays key roles in several neurodevelopmental disorders and actions of pharmacological treatments. However, it is unclear how specific BDNF’s effects are on different circuit components. Current studies have largely focused on the role of BDNF in modification of synaptic development. The precise roles of BDNF in the refinement of a functional circuit in vivo remain unclear. Val66Met polymorphism of BDNF may be associated with increased risk for cognitive impairments and is mediated at least in part by activity-dependent trafficking and/or secretion of BDNF. Using mutant mice that lacked activity-driven BDNF expression (bdnf-KIV), we previously reported that experience regulation of the cortical GABAergic network is mediated by activity-driven BDNF expression. Here, we demonstrate that activity-driven BDNF’s effects on circuits formed by the layer IV spiny stellate cells are highly specific. Structurally, dendritic but not axonal morphology was altered in the mutant. Physiologically, GABAergic but not glutamatergic synapses were severely affected. The effects on GABA transmission occurs via presynaptic alteration of calcium-dependent release probability. These results suggest that neuronal activity through activity-driven BDNF expression, can selectively regulate specific features of layer IV circuits in vivo. We postulate that the role of activity-dependent BDNF is to modulate the computational ability of circuits that relate to the gain control (i.e., feed-forward inhibition); whereas the basic wiring of circuits relevant to the sensory pathway is spared. Gain control modulation within cortical circuits has broad impact on cognitive processing and brain state-transitions. Cognitive behavior and mode is determined by brain states, thus the studying of circuit alteration by endogenous BDNF provides insights into the cellular and molecular mechanisms of diseases mediated by BDNF. PMID:25414642

  10. Characterization of recombinantly expressed dihydroxy-acid dehydratase from Sulfobus solfataricus-A key enzyme for the conversion of carbohydrates into chemicals.

    PubMed

    Carsten, Jörg M; Schmidt, Anja; Sieber, Volker

    2015-10-10

    Dihydroxyacid dehydratases (DHADs) are excellent biocatalysts for the defunctionalization of biomass. Here, we report on the recombinant production of DHAD from Sulfolobus solfataricus (SsDHAD) in E. coli and its characterization with special focus on activity toward non-natural substrates, thermo-stability, thermo-inactivation kinetics and activation capabilities and its application within multi-step cascades for chemicals production. Using a simple heat treatment of cell lysate as major purification step we achieved a specific activity of 4.4 units per gram cell mass toward the substrate d-gluconate. The optimal temperature and pH value for this reaction are 77°C and pH 6.2. The inhibitory concentration (IC50, 50% residual activity) of different alcohols was determined to be 15% (v/v) for ethanol, 4.5% (v/v) for butanol and 4% (v/v) for isobutanol. Besides d-gluconate and the natural substrate 2,3-dihydroxyisovalerate (DHIV) SsDHAD is able to convert the C3-sugar-acid d-glycerate to pyruvate, a reaction, which does not occur in natural metabolic pathways, with a specific activity of 10.7±0.4mU/mg. The specific activity of the enzyme can be increased 3-fold by incubation with 2-mercaptoethanol. The activation has no impact on temperature dependence, but modulates the thermo-inactivation tolerance at 50°C. The total turnover numbers for all of the three reactions was found to be 35.5×10(3)±1.0×10(3) for the conversion of d-gluconate to 2-keto-3-deoxygluconate (KDG), 28.2×10(3)±0.8×10(3) for DHIV to 2-ketovalerate (KIV) and 943±0.28×10(2) for d-glycerate to pyruvate. With activated SsDHAD these values could be further increased 5- and 4-fold for the d-gluconate and d-glycerate conversion, respectively.

  11. State of oral cavity hygiene, sIgA level, mineral content of oral fluid, and optimization of preventive intervention in children with enamel hypoplasia and underlying comorbidity.

    PubMed

    Liubarets, S F; Kopylova, O V; Belingio, T O; Kolbasynska, V M; Sechina, I M; Liubarets, T F

    2015-12-01

    Meta doslidzhennia. Pidvyshchyty efektyvnist' profilaktyky kariiesu u ditey z gipoplaziieiu emali shliakhom vprovad zhennia kompleksu zakhodiv, spriamovanykh na optymizatsiiu gigiieny porozhnyny rota, rivnia sIgA ta vmistu mineral' nykh skladovykh rotovoI ridyny.Materialy i metody. Ob’iekt doslidzhennia – gipoplaziia emali postiynykh zubiv. Predmet doslidzhennia – gigiienichnyy stan porozhnyny rota, sekretornyy imunoglobulin klasu A (sIgA), riven' zagal'nogo kal'tsiiu ta ortofosfativ v rotoviy ridyni. Metody doslidzhennia: vital'ne zabarvlennia emali, transiliuminatsiynyy, imunofermentnyy ta fo tometrychnyy metody, pokaznyky gigiienichnogo stanu porozhnyny rota (indeks Green Vermillion (1964), indeks Silness Loe (1964, 1967)). Provedena otsinka gigiienichnogo stanu porozhnyny rota ta vyznachennia rivnia sIgA, kal'tsiiu ta ortofosfativ v rotoviy ridyni 43 ditey vikom 6–14 rokiv (grupa No 1 – 21 osoba, grupa No 2 – 22 oso by) z systemnoiu gipoplaziieiu emali na tli dyfuznogo netoksychnogo vola, eutyreozu, narodzhenykh vid bat'kiv – uchasnykiv likvidatsiI naslidkiv avariI na ChAES ta evakuyovanykh z terytoriy obov’iazkovogo vidselennia. Grupa No 1 – dity, iakym pryznachavsia kompleks profilaktychnykh zakhodiv, shcho vkliuchav rekomendatsiI shchodo vyboru zasobiv i predmetiv dlia dogliadu za porozhnynoiu rota ta navchannia standartnomu metodu chyshchennia zubiv. Grupa No 2 – dity, u iakykh dodatkovo zastosovuvaly remineralizuiuchyy gel', shcho mistyt' kal'tsiy, fosfor, magniy ta ksylit („Vysno vok DerzhavnoI sanitarno epidemiologichnoI sluzhby UkraIny No05.03.02 03/9351 vid 07.02.2014r. ”). Rezul'taty. Gigiienichnyy stan porozhnyny rota ditey obokh grup buv otsinenyy zgidno z kryteriiem „nezadovil'nyy ” indeksu Green Vermillion ta kryteriiem „poganyy ” indeksu Silness Loe. Pislia provedennia profilaktychnykh zakhodiv u ditey grup No 1 ta No 2 pokrashchyvsia gigiienichnyy stan porozhnyny rota: suttieve znyzhennia indeksu Green Vermillion

  12. Characterization of recombinantly expressed dihydroxy-acid dehydratase from Sulfobus solfataricus-A key enzyme for the conversion of carbohydrates into chemicals.

    PubMed

    Carsten, Jörg M; Schmidt, Anja; Sieber, Volker

    2015-10-10

    Dihydroxyacid dehydratases (DHADs) are excellent biocatalysts for the defunctionalization of biomass. Here, we report on the recombinant production of DHAD from Sulfolobus solfataricus (SsDHAD) in E. coli and its characterization with special focus on activity toward non-natural substrates, thermo-stability, thermo-inactivation kinetics and activation capabilities and its application within multi-step cascades for chemicals production. Using a simple heat treatment of cell lysate as major purification step we achieved a specific activity of 4.4 units per gram cell mass toward the substrate d-gluconate. The optimal temperature and pH value for this reaction are 77°C and pH 6.2. The inhibitory concentration (IC50, 50% residual activity) of different alcohols was determined to be 15% (v/v) for ethanol, 4.5% (v/v) for butanol and 4% (v/v) for isobutanol. Besides d-gluconate and the natural substrate 2,3-dihydroxyisovalerate (DHIV) SsDHAD is able to convert the C3-sugar-acid d-glycerate to pyruvate, a reaction, which does not occur in natural metabolic pathways, with a specific activity of 10.7±0.4mU/mg. The specific activity of the enzyme can be increased 3-fold by incubation with 2-mercaptoethanol. The activation has no impact on temperature dependence, but modulates the thermo-inactivation tolerance at 50°C. The total turnover numbers for all of the three reactions was found to be 35.5×10(3)±1.0×10(3) for the conversion of d-gluconate to 2-keto-3-deoxygluconate (KDG), 28.2×10(3)±0.8×10(3) for DHIV to 2-ketovalerate (KIV) and 943±0.28×10(2) for d-glycerate to pyruvate. With activated SsDHAD these values could be further increased 5- and 4-fold for the d-gluconate and d-glycerate conversion, respectively. PMID:26102631

  13. Strategies towards advanced ion track-based biosensors

    NASA Astrophysics Data System (ADS)

    Alfonta, L.; Bukelman, O.; Chandra, A.; Fahrner, W. R.; Fink, D.; Fuks, D.; Golovanov, V.; Hnatowicz, V.; Hoppe, K.; Kiv, A.; Klinkovich, I.; Landau, M.; Morante, J. R.; Tkachenko, N. V.; Vacík, J.; Valden, M.

    Three approaches towards ion track-based biosensors appear to be feasible. The development of the first one began a decade ago [Siwy, Z.; Trofin, L.; Kohl, P.; Baker, L.A.; Martin, C.R.; Trautmann, C. J. Am. Chem. Soc. 2005, 127, 5000-5001; Siwy, Z.S.; Harrell, C.C.; Heins, E.; Martin, C.R.; Schiedt, B.; Trautmann, C.; Trofin, L.; Polman, A. Presented at the 6th International Conference on Swift Heavy Ions in Matter, Aschaffenburg, Germany, May 28-31, 2005] and makes use of the concept that the presence of certain biomolecules within liquids can block the passage through narrow pores if being captured there, thus switching off the pore's electrical conductivity. The second, having been successfully tested half a year ago [Fink, D.; Klinkovich, I.; Bukelman, O.; Marks, R.S.; Fahrner, W.; Kiv, A.; Fuks, D.; Alfonta, L. Biosens. Bioelectron. 2009, 24, 2702-2706], is based on the accumulation of enzymatic reaction products within the confined volume of narrow etched ion tracks which modifies the pore's electrical conductivity. The third and most elegant, at present under development, will exploit the charge transfer from enzymes to semiconductors embedded within etched tracks, enabling the enzymes undergoing specific reactions with the biomolecules to be detected. These strategies can be realized either within carrier-free nanoporous polymeric membranes embedded in the corresponding bioliquids, or within contacted nanoporous insulating layers on semiconducting substrates, the so-called TEMPOS structures [Fink, D.; Petrov, A.; Hoppe, H.; Fahrner, W.R.; Papaleo, R.M.; Berdinsky, A.; Chandra, A.; Biswas, A.; Chadderton, L.T. Nucl. Instrum. Methods B 2004, 218, 355-361]. The latter have the advantage of exhibiting a number of peculiar electronic properties, such as the ability for logic and/or combination of input signals, tunable polarity, negative differential resistances, tunability by external parameters such as light, magnetic fields, etc. and self-pulsations, which

  14. The CaMKK2/CaMKIV Relay Is an Essential Regulator of Hepatic Cancer

    PubMed Central

    Lin, Fumin; Marcelo, Kathrina L.; Rajapakshe, Kimal; Coarfa, Cristian; Dean, Adam; Wilganowski, Nathaniel; Robinson, Holly; Sevick, Eva; Bissig, Karl-Dimiter; Goldie, Lauren C.; Means, Anthony R.; York, Brian

    2015-01-01

    Hepatic cancer is one of the most lethal cancers worldwide. Here, we report that the expression of Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is significantly up-regulated in hepatocellular carcinoma (HCC) and negatively correlated with HCC patient survival. The CaMKK2 protein is highly expressed in all eight hepatic cancer cell lines evaluated and is markedly up-regulated relative to normal primary hepatocytes. Loss of CaMKK2 function is sufficient to inhibit liver cancer cell growth, and the growth defect resulting from loss of CaMKK2 can be rescued by ectopic expression of wild-type CaMKK2 but not by kinase-inactive mutants. Cellular ablation of CaMKK2 using RNA interference yields a gene signature that correlates with improvement in HCC patient survival, and ablation or pharmacological inhibition of CaMKK2 with STO-609 impairs tumorigenicity of liver cancer cells in vivo. Moreover, CaMKK2 expression is up-regulated in a time-dependent manner in a carcinogen-induced HCC mouse model, and STO-609 treatment regresses hepatic tumor burden in this model. Mechanistically, CaMKK2 signals through Ca2+/calmodulin-dependent protein kinase 4 (CaMKIV) to control liver cancer cell growth. Further analysis revealed that CaMKK2 serves as a scaffold to assemble CaMKIV with key components of the mammalian target of rapamycin/ribosomal protein S6 kinase, 70 kDa, pathway and thereby stimulate protein synthesis through protein phosphorylation. Conclusion The CaMKK2/CaMKIV relay is an upstream regulator of the oncogenic mammalian target of rapamycin/ribosomal protein S6 kinase, 70 kDa, pathway, and the importance of this CaMKK2/CaM-KIV axis in HCC growth is confirmed by the potent growth inhibitory effects of genetically or pharmacologically decreasing CaMKK2 activity; collectively, these findings suggest that CaMKK2 and CaMKIV may represent potential targets for hepatic cancer. PMID:25847065

  15. [Urgent laparoscopic adrenalectomy in acute crisis caused by pheochromocytoma].

    PubMed

    Bereczky, Bíborka; Madách, Krisztina; Gál, János; István, Gábor; Sugár, István; Ondrejka, Pál; Vörös, Attila

    2014-06-01

    Esetismertetés: A szerzők egy 30 éves nőbeteg esetét mutatják be, akinek intenzív osztályos felvételére hypertoniás krízist kísérő mellkasi panaszok, cardialis decompensatio, progrediáló acut légzési elégtelenség és tudatzavar miatt került sor. A gyors kivizsgálás mellett azonnal megkezdett intenzív terápia ellenére a felvételt követő harmadik napra többszervi elégtelenség képe alakult ki. Miután a kórkép kialakulása a bal oldali mellékvese térfoglaló folyamatára volt visszavezethető, a multidiszciplináris konzílium acut laparoscopos adrenalectomia végzése mellett foglalt állást. Az eltávolított képlet szövettani diagnózisa phaeochromocytoma volt. A postoperativ időszakban a beteg állapota fokozatosan javult, tünetei, panaszai regrediáltak, majd gyógyultan távozott. Megbeszélés: A phaeochromocytoma diagnózisa nehéz feladat, az általa kiváltott tünetek és panaszok sok egyéb kórképre is utalhatnak. Az acut phaeochromocytomás krízis általában belgyógyászati, intenzív terápiás eszközökkel uralható. A súlyos, többszervi elégtelenséghez vezető esetekben indokolt az acut műtéti beavatkozás. Az ilyen beavatkozások rizikója igen magas, de korrekt intra- és postoperativ észleléssel, megfelelő intenzív terápiával a laparoscopos műtét ezekben az esetekben választható megoldás lehet.

  16. [Lipid-lowering therapy and patient adherence in the MULTI GAP 2013 trial].

    PubMed

    Simonyi, Gábor

    2014-04-27

    Bevezetés: A dyslipidaemia ismert cardiovascularis kockázati tényező. A lipidterápiában a célértékek elérésének fontos tényezője a megfelelő betegadherencia. Célkitűzés: A MULTI GAP (MULTI Goal Attainment Problem) 2013-as vizsgálatban atheroscleroticus betegségben szenvedő betegek esetében a statinterápia adherenciájának és perzisztenciájának felmérése, amely részben a vizsgálatban részt vevő orvosok becslésén, illetve 319, a megelőző évben elvégzett MULTI GAP vizsgálatban részt vett beteg esetében az Országos Egészségbiztosítási Pénztár vénykiváltási adatbázisán alapult. Módszer: A MULTI GAP 2013 vizsgálatban standard, strukturált kérdőívek segítségével 1519 beteg adatai kerültek feldolgozásra. Az elemzésben kiértékelésre kerültek az egyes ellátási szinteken elért lipidértékek, a kezelőorvos által vélt betegadherencia, a 319 beteg Országos Egészségbiztosítási Pénztár vénykiváltási adataira támaszkodó valós adherencia, a kezelőorvosok elégedettsége a statinterápia eredményeivel, illetve az adherencia és a lipideredmények összevetése. Eredmények: Az elmúlt 7 év felméréseinek adatait is figyelembe véve előtérbe kerültek a hatékonyabb statinok; az atorvastatin és rozuvastatin alkalmazásának összesített aránya 49%-ról 83%-ra, azaz mintegy 70%-kal nőtt. A betegadherencia vonatkozásában kimutatták, hogy a 2,5 mmol/l alatti LDL-koleszterin-értékeket elért betegeknél az 1 év alatt kiváltott receptek száma mintegy nyolc gyógyszertári beváltást jelentett. Ehhez képest a 2,5 mmol/l feletti LDL-koleszterin-értékű csoportban a gyógyszerkiváltás lényegesen alacsonyabb volt (5,3 és 6,3 közötti). Éves szinten a 10–12 és a 7–9 gyógyszerkiváltás szignifikánsan alacsonyabb LDL-koleszterin-szintet jelentett a semennyit (0), illetve az 1–3 receptet éves szinten kiváltók csoportjaihoz képest. A kezelőorvosok által 100%-os

  17. [Connection between cancer- and alcohol-related mortality in a rural practice of a South-Hungarian village].

    PubMed

    Péter, Arpád

    2013-05-01

    Bevezetés: A több mint negyedszázada ugyanazon egykörzetes községben dolgozó szerző az 1987 és 1999 közötti vizsgálati periódusban a daganatos halálozásnak az alkohollal kapcsolatos halálozással összefüggő hányadát férfiak körében 50%-nak, nők körében 7,9%-nak találta. Célkitűzés: A szerző célként tűzte ki a halálozás e két meghatározó tényezőjének hosszabb távú nyomon követéséhez és elemzéséhez a halálozási mutatók ismételt felmérését a 2000 és 2011 közötti időszakra vonatkozóan. Módszer: Az elhunyt betegek valamennyi fontos előzményi adatát összefoglaló háziorvosi halotti epikrízisekbe tömörítette és a halálokok kiválasztásakor ezeket döntő súllyal vette figyelembe. Eredmények: A vizsgált 12 év alatt a szerző úgynevezett „tisztított praxislakossága” körében 326 ember halt meg (167 férfi, 159 nő). Bár a részeredményeket tekintve is jelentős átstruktúrálódás következett be a daganatos és alkoholos halálozási kategóriákon belül, és ezek összes halálozáson belüli aránya is megváltozott (az alkohollal kapcsolatos halálozásé számottevően csökkent, míg a daganatos halálozásé kisebb mértékben nőtt), az újabb vizsgálati periódusban a daganatos halálozásnak alkohollal kapcsolatos hányada mindkét nemben nőtt (a férfiak körében 60%-ra, a nők körében 9,1%-ra). Következtetés: Legfőbb epidemiológiai következtetésként megerősítést nyert, hogy a daganatos betegségek megelőzésének, különösen bizonyos lokalizációjú daganatok mint halálokok csökkentésének egyik kulcskérdése – megkülönböztetetten a férfiak körében – az alkoholabúzus visszaszorítása. Orv. Hetil., 2013, 154, 700–706.

  18. [Cognitive functions in type 1 and type 2 diabetes. Meta-analysis].

    PubMed

    Kálcza-Jánosi, Kinga; Lukács, Andrea; Barkai, László; Szamosközi, István

    2013-05-01

    Bevezetés: A cukorbetegséget különféle kognitív károsodásokkal társítják. Célkitűzés: A szerzők 1-es és 2-es típusú diabetesben a kognitív működés közötti különbségek pontosítását tűzték ki célul. Módszer: Metaanalízis a Medline, PubMed és ScienceDirect felhasználásával (három tanulmány az 1-es és hat tanulmány a 2-es típusú cukorbetegséggel kapcsolatban). Eredmények: Az 1-es típusú cukorbeteg felnőttek teljesítménye gyengébb volt a kontrollokhoz képest az összes mért területen. A hatásméret a pszichomotoros aktivitásnál volt a legmagasabb (D = –0,69). Kicsi volt a hatásméret a késleltetett verbális memória (D = –0,48), figyelem (D = –0,47), nyelv (D = –0,44), vizuális feldolgozás (D = –0,35), azonnali verbális memória (D = –0,30), munkamemória (D = –0,27) és a végrehajtó funkcióknál (D = –0,26). A felnőtt 2-es típusú cukorbetegek teljesítménye gyengébb volt, mint a kontrolloké a munkamemória kivételével (D = +0,03) az összes kognitív területen. Legmagasabb hatásméretet az azonnali verbális memória (D = –1,12), pszichomotoros aktivitás (D = –0,82) és a késleltetett verbális memória (D = –0,81) mutatott. Közepes volt a hatásméret az általános intellektuális képességek (D = –0,68) területén, míg kicsi volt a hatásméret az általános memória (D = –0,37), a figyelem (D = –0,35), nyelv (D = –0,35), vizuális feldolgozás (D = –0,33) és a végrehajtó funkciók (D = –0,33) terén. Következtetés: Mindkét típusú cukorbetegség csökkent teljesítménnyel társul számos kognitív területen. Orv. Hetil., 2013, 154, 694–699.

  19. [Changing times - changing diseases. Review of the neuropathological autopsy documentations at the Markusovszky University Teaching Hospital (1964-2014)].

    PubMed

    Garzuly, Ferenc; Schneider, Ferenc; Iványi, János László; Nagy, Zsuzsanna; Varga, Mariann; Sütő, Krisztián; Tolvaj, Balázs; Kálmán, Bernadette

    2014-10-26

    Bevezetés: A Markusovszky Egyetemi Oktatókórház Neuropatológiai Laboratóriumában az elmúlt 50 évben közel 6000 esetben történt autopsziás vizsgálat. Célkitűzés: A szerzők célja azon korábban gyakori, magas mortalitású betegségek bemutatása, amelyek ma már megelőzhetőek vagy kezelhetőek. Módszer: A neuropatológiai dokumentáció retrospektív áttekintése. Eredmények: A morbilli vírusa okozta szubakut szklerotizáló panencephalitis miatt 13 beteg halt meg, az utolsó haláleset 1991-ben volt. A kötelező védőoltás bevezetése vetett véget a halálos megbetegedésnek. Herpes simplex encephalitis miatt 14-en vesztették életüket, az utolsó 1999-ben. A korai diagnosztizálás feltételeinek javulása és az aciclovirkezelés tette lehetővé a halálesetek elkerülését. Meningitis basilaris tuberculosa szórványosan, de az utóbbi években is előfordult. Felismerése nem könnyű, ritkasága miatt kikerült a rutindiagnosztika gondolatmenetből. Kullancsencephalitisben a védőoltások elérhetővé válása folyamatosan tovább csökkentette a különben is ritka, összesen 8 esetben dokumentált halálos esetek számát. Fatális kimenetelű neuroluessel az 1990-es években találkoztak utoljára, de a syphilis nem tűnt el, sőt a friss fertőzések száma emelkedik. A meningiosis leukaemica kivédését az intrathecalis methotrexat adása és radioterápia tette lehetővé, amelyek alkalmazása azonban óvatosságot igényel, a szerzők esetei között is jegyzett disszeminált nekrotizáló leukoencephalopathia kialakulásának lehetősége miatt. Következtetések: A Neuropatológiai Laboratórium 50 éves dokumentációja tükrözi a betegségek előfordulásának változásait, és felhívja a figyelmet azokra a kórképekre, amelyek ma már megelőzhetők vagy kezelhetők, de diagnosztikus kihívást is jelenthetnek. Orv. Hetil., 2014, 155(43), 1722–1728.

  20. [Use of hysteroscopy at the office in gynaecological practice].

    PubMed

    Török, Péter

    2014-10-01

    Bevezetés: Az office hiszteroszkópia a méhűri vizsgálatot gyorsabbá teszi, alacsonyabb költségigényű, a betegek számára pedig kevesebb megterheléssel jár. Célkitűzés: A szerző célja volt a vizsgálatok közben tapasztalt fájdalomérzetek elemzése, új eljárás kidolgozása a petevezető-átjárhatóság ambuláns vizsgálatára. Módszer: A vizsgálatok a Debreceni Egyetem, Szülészeti és Nőgyógyászati Klinikáján történtek, ambuláns körülmények között, anesztézia nélkül. A 400 vizsgálat eredményének elemzése a hagyományos módszernél ismert javallatok alapján készült. A szerző a vizsgálatokhoz 2,7 mm átmérőjű optikát használt diagnosztikus, illetve operatív hüvellyel, és a fájdalomérzet objektivizálására 70 betegnél VAS-t alkalmazott. A petevezető-átjárhatósági vizsgálat során 70 esetben hasonlította az új módszert a laparoszkópos változathoz. Eredmények: Az office hiszteroszkópia alkalmazható ambuláns körülmények között, anesztézia nélkül. A tapasztalt fájdalomértékek az alcsoportokban (nem szült, szült, posztmenopauza, diagnosztikus/operatív alcsoport) szignifikánsan nem különböztek, átlagértékük 3,5±1,01 volt (p=0,34). A szelektív pertubáció a laparoszkópos kromohidrotubációhoz viszonyítva 92,06% pontosságúnak bizonyult. Következtetések: Az office hiszteroszkópia gyorsasága, fájdalommentessége az új eljárás széles körű alkalmazását támasztja alá. Meddőségi kivizsgálásban kiválthatja a műtői körülményeket igénylő beavatkozásokat. Orv. Hetil., 2014, 155(40), 1589–1597.

  1. [Effectiveness of pentoxifylline and of bio-electromagnetic therapy in lower limb obliterative arterial disease].

    PubMed

    Bernát, Sándor Iván

    2013-10-20

    Bevezetés: A mikrocirkuláció javítására korlátozottak a terápiás lehetőségek. Célkitűzés: A vizsgálat elsősorban arra irányult, hogy bizonyítható-e a változó mágneses tér kedvező hatása az alsó végtagi obliteratív érbetegségben szenvedő betegek mikrokeringésére. Módszer: Harminc, alsó végtagi obliteratív érbetegségben (Fontaine IIa és IIb) szenvedő beteget vontak be a vizsgálatba. Megmérték a betegek fájdalmatlan és maximális járástávolságát treadmill készülék segítségével. Placeboperiódust követően nyolc alkalommal részesültek a betegek bioelektromágnes-regulációs terápiában, majd infúziós pentoxifillinterápiában, és minden kezelés után megmérték a betegek fájdalommentes és maximális járástávolságát. Eredmények: A bioelektromágnes-regulációs kezelés hatására a fájdalommentes és maximális járástávolság 57,4%-kal (p = 0,005), illetve 36,6%-kal (p = 0,042) nőtt. A kombinált (bioelektromágnes-regulációs+reológiai) kezelés összesen 81,9%-kal, illetve 84,0%-kal növelte a mért értékeket. A kombinált kezelés a terápia előttihez képest jelentős mértékben javította a járásképességet (p = 0,000373 és p = 0,00741). Következtetések: A bioelektromágnes-regulációs terápia elsősorban a mikrokeringés ereire, a pentoxifillin inkább a haemorrheologiára hat kedvezően. A kombinált kezelés jól kiegészíti egymást, és 70%-ban jó, illetve kiváló terápiás hatást eredményez. Orv. Hetil., 2013, 154, 1674–1679.

  2. [Comparison of the effectiveness of two internationally recommended screening methods for the diagnosis of gestational diabetes].

    PubMed

    Salamon, Mónika; Soós, Zsuzsanna; Oláh, Roland; Hazai, Máté; Sóvágó, László; Kovács, Dóra; Pál, Borbála; Baranyi, Eva; Lintner, Ferenc; Winkler, Gábor

    2013-05-19

    Bevezetés: A terhességi cukorbetegség időben történő felismerése és megfelelő kezelése az anya és a magzat számára egyaránt kiemelkedő fontosságú. Noha nemzetközi és nemzeti szaktársasági állásfoglalások születtek az időben történő felismerés módszertanáról, az esetek egy része az Egészségügyi Világszervezet által ajánlott (1. ajánlás) s ma legáltalánosabban használt módszerrel is rejtve maradhat. Több vizsgálatban összefüggést találtak az anyai vércukorszint és a halvaszülések, a praeeclampsia-előfordulás, illetve a születési időre számított nagy súlyú újszülöttek világrahozatala között, a legnagyobb visszhangot a Hyperglycemia and Adverse Pregnancy Outcomes vizsgálat hozta. Megállapításai nyomán a Diabéteszes Terhességgel Foglalkozó Munkacsoportok Nemzetközi Szövetsége a 75 grammos cukorterhelésen alapuló, de az 1. ajánlásban szereplőtől eltérő kritériumrendszerű szűrést javasolt (2. ajánlás). Célkitűzés: A vizsgálat célja várandósok terhességi kimenetelének elemzésével a két szűrési eljárás hatékonyságának összevetése volt. Módszerek: Egyszeres terhességet hordozó 1107 várandóst, 831 normális glükóztoleranciájú és 276, a két szűrés valamelyikével gestatiós diabetesesnek minősülő terhest vizsgáltak, részletesen elemezve a terhességi kimenetel anyai (koraszülés, túlhordás, sectio caesarea, toxaemia) és magzati mutatóit (születési súly, újszülöttkori hypoglykaemia). Eredmények: A születési időre számított nagy súlyú magzatok prevalenciája kivételével – melynek csökkentésében a 2. ajánlás, illetve az ennek alapján megkezdett gondozás hatékonyabbnak bizonyult – a két szűrési eljárás eredményességében érdemi különbség nem volt kimutatható. Következtetés: Az új ajánlás szerinti szűrés a glükózanyagcsere-zavar biztonságosabb felismerését eredményezheti, az egyértelmű

  3. [Medication adherence with the fixed combination of ramipril and amlodipine].

    PubMed

    Simonyi, Gábor; Ferenci, Tamás

    2014-11-23

    Bevezetés: Az olyan krónikus betegségek, mint a hypertonia kezelése során is kiemelkedő jelentőséggel bír a megfelelő betegadherencia, mivel csak tartós és hatásos gyógyszerszedés segítségével érhető el a célvérnyomás és a cardiovascularis kockázat csökkenése. Jól ismert, hogy a hypertonia az egyik legfontosabb cardiovascularis kockázati tényező. Nemzetközi adatok szerint a fix kombinációval végzett antihipertenzív terápia mintegy 20%-kal javítja a betegadherenciát a szabad kombinációhoz képest. Célkitűzés: A szerzők célja a hypertoniaindikációban indított ramipril és amlodipin szabad és fix kombinációk egyéves perzisztenciájának összehasonlítása volt. Módszer: Az Országos Egészségbiztosítási Pénztár adatbázisából a vényforgalmi adatokra támaszkodva hypertoniaindikációban, 2012. október 1. és 2013. szeptember 30. között első alkalommal ramipril és amlodipin szabad, illetve ramipril és amlodipin fix kombináció receptjeit kiváltó betegeket választották ki, akik az ezt megelőző egy évben hasonló hatóanyaggal végzett antihipertenzív terápiában nem részesültek. A perzisztenciagörbéket Kaplan–Meier-becsléssel határozták meg, 95%-os, log-skálán számolt pontonkénti konfidenciaintervallummal. Cenzoráltnak azokat a betegeket vették, akik a vizsgálat záró időpontjában is perzisztensek voltak. A görbék modellezéséhez félparaméteres eljárást, Cox-regressziót használtak, ahol az egyetlen – kategoriális – magyarázó változó a terápia volt; referenciacsoportnak a fix kombinációt vették. Eredmények: A vizsgált időszakban 20 096 beteg kezdett ramipril és amlodipin szabad kombinációs, míg 10 449 beteg kezdett ramipril és amlodipin fix kombinációs antihipertenzív terápiát. A megfigyelési időszakban a ramipril és az amlodipin szabad kombinációja esetén az egyéves perzisztencia 34%-os volt, míg a fix kombinációt szedőknél ez

  4. [Low persistence of simvastatin and ezetimibe fixed combination in the lipid lowering therapy].

    PubMed

    Simonyi, Gábor; Ferenci, Tamás

    2015-01-25

    Bevezetés: Jól ismert, hogy a magas koleszterinszint fontos módosítható cardiovascularis kockázati tényező. A lipidcsökkentő kezelés során a cardiovascularis kockázat csökkentése miatt fontos a betegek terápiahűsége. Célkitűzés: A szerzők célja a simvastatin/ezetimib szabad és fix kombinációk, illetve a leghatékonyabb statin, a rozuvastatin egyéves perzisztenciájának összehasonlítása volt. Módszer: Az Országos Egészségbiztosítási Pénztár vényforgalmi adataira támaszkodva 2012. október 1. és 2013. szeptember 30. között első alkalommal a simvastatin/ezetimib szabad és fix kombinációi és a rozuvastatinmonoterápia receptjeit kiváltó betegeket választották ki, akik az ezt megelőző egy évben hasonló hatóanyaggal végzett antilipaemiás terápiában nem részesültek. A perzisztenciagörbéket Kaplan–Meier-becsléssel határozták meg, 95%-os, log-skálán számolt pontonkénti konfidenciaintervallummal. Cenzoráltnak azokat a betegeket vették, akik a vizsgálat záró időpontjában is perzisztensek voltak. A görbék modellezéséhez félparaméteres eljárást, Cox-regressziót használtak, ahol az egyetlen – kategoriális – magyarázó változó a terápia volt; referenciacsoportnak a simvastatin/ezetimib fix kombinációt vették. Eredmények: A bevonási kritériumoknak összesen 204 699 beteg felelt meg. E betegek közül 10 030 beteg kezdett simvastatin/ezetimib szabad, 7613 beteg simvastatin/ezetimib fix, illetve 187 056 beteg rozuvastatinmonoterápiát. Az egyéves perzisztencia a simvastatin/ezetimib szabad kombináció esetében 10,97%, a simvastatin/ezetimib fix kombinációt szedőkben 24,35%, míg a rozuvastatinmonoterápián lévők esetében 30,47% volt. A simvastatin/ezetimib fix kombinációhoz képest a simvastatin/ezetimib szabad kombináció elhagyásának az esélye 73%-kal volt nagyobb (kockázatarány = 1,73 [95% konfidenciaintervallum: 1,61–1,85], p<0,0001), míg a