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Sample records for normal extracellular levels

  1. Formation of neutrophil extracellular traps under low oxygen level

    Directory of Open Access Journals (Sweden)

    Katja Branitzki-Heinemann

    2016-11-01

    Full Text Available Since their discovery, neutrophil extracellular traps (NETs have been characterized as a fundamental host innate immune defense mechanism. Conversely, excessive NET release may have a variety of detrimental consequences for the host. A fine balance between NET formation and elimination is necessary to sustain a protective effect during an infectious challenge. Our own recently published data revealed that stabilization of hypoxia inducible factor 1α (HIF-1α by the iron chelating HIF-1α-agonist desferoxamine or AKB-4924 enhanced the release of phagocyte extracellular traps. Since HIF-1α is a global regulator of the cellular response to low oxygen, we hypothesized that NET formation may be similarly increased under low oxygen conditions. Hypoxia occurs in tissues during infection or inflammation, mostly due to overconsumption of oxygen by pathogens and recruited immune cells. Therefore, experiments were performed to characterize the formation of NETs under hypoxic oxygen conditions compared to normoxia. Human blood-derived neutrophils were isolated and incubated under normoxic (21% oxygen level and compared to hypoxic (1% conditions. Dissolved oxygen levels were monitored in the primary cell culture using a Fibox4-PSt3 measurement system. The formation of NETs was quantified by fluorescence microscopy in response to the known NET-inducer phorbol 12-myristate 13-acetate (PMA or S. aureus wildtype and a nuclease-deficient mutant. In contrast to our hypothesis, spontaneous NET formation of neutrophils incubated under hypoxia was distinctly reduced compared to control neutrophils incubated under normoxia. Furthermore, neutrophils incubated under hypoxia showed significantly reduced formation of NETs in response to PMA. Gene expression analysis revealed that mRNA level of hif-1α as well as hif-1α target genes was not altered. However, in good correlation to the decreased NET formation under hypoxia, the cholesterol content of the neutrophils was

  2. Hemoglobin levels in normal Filipino pregnant women.

    Science.gov (United States)

    Kuizon, M D; Natera, M G; Ancheta, L P; Platon, T P; Reyes, G D; Macapinlac, M P

    1981-09-01

    The hemoglobin concentrations during pregnancy in Filipinos belonging to the upper income group, who were prescribed 105 mg elemental iron daily, and who had acceptable levels of transferrin saturation, were examined in an attempt to define normal levels. The hemoglobin concentrations for each trimester followed a Gaussian distribution. The hemoglobin values equal to the mean minus one standard deviation were 11.4 gm/dl for the first trimester and 10.4 gm/dl for the second and third trimesters. Using these values as the lower limits of normal, in one group of pregnant women the prevalence of anemia during the last two trimesters was found lower than that obtained when WHO levels for normal were used. Groups of women with hemoglobin of 10.4 to 10.9 gm/dl (classified anemic by WHO criteria but normal in the present study) and those with 11.0 gm/dl and above could not be distinguished on the basis of their serum ferritin levels nor on the degree of decrease in their hemoglobin concentration during pregnancy. Many subjects in both groups, however, had serum ferritin levels less than 12 ng/ml which indicate poor iron stores. It might be desirable in future studies to determine the hemoglobin cut-off point that will delineate subjects who are both non-anemic and adequate in iron stores using serum ferritin levels as criterion for the latter.

  3. Brain infection with Staphylococcus aureus leads to high extracellular levels of glutamate, aspartate, γ-aminobutyric acid, and zinc.

    Science.gov (United States)

    Hassel, Bjørnar; Dahlberg, Daniel; Mariussen, Espen; Goverud, Ingeborg Løstegaard; Antal, Ellen-Ann; Tønjum, Tone; Maehlen, Jan

    2014-12-01

    Staphylococcal brain infections may cause mental deterioration and epileptic seizures, suggesting interference with normal neurotransmission in the brain. We injected Staphylococcus aureus into rat striatum and found an initial 76% reduction in the extracellular level of glutamate as detected by microdialysis at 2 hr after staphylococcal infection. At 8 hr after staphylococcal infection, however, the extracellular level of glutamate had increased 12-fold, and at 20 hr it had increased >30-fold. The extracellular level of aspartate and γ-aminobutyric acid (GABA) also increased greatly. Extracellular Zn(2+) , which was estimated at ∼2.6 µmol/liter in the control situation, was increased by 330% 1-2.5 hr after staphylococcal infection and by 100% at 8 and 20 hr. The increase in extracellular glutamate, aspartate, and GABA appeared to reflect the degree of tissue damage. The area of tissue damage greatly exceeded the area of staphylococcal infiltration, pointing to soluble factors being responsible for cell death. However, the N-methyl-D-aspartate receptor antagonist MK-801 ameliorated neither tissue damage nor the increase in extracellular neuroactive amino acids, suggesting the presence of neurotoxic factors other than glutamate and aspartate. In vitro staphylococci incubated with glutamine and glucose formed glutamate, so bacteria could be an additional source of infection-related glutamate. We conclude that the dramatic increase in the extracellular concentration of neuroactive amino acids and zinc could interfere with neurotransmission in the surrounding brain tissue, contributing to mental deterioration and a predisposition to epileptic seizures, which are often seen in brain abscess patients. © 2014 Wiley Periodicals, Inc.

  4. Role of Stroma-Derived Extracellular Matrix in Regulation of Growth and Hormonal Responsiveness of Normal and Cancerous Human Breast Epithelium

    National Research Council Canada - National Science Library

    Woodward, Terry

    1997-01-01

    Specific extracellular matrix (ECM) proteins and their cellular receptors (integrins) are required for normal mammary gland morphogenesis and differentiation, while their expression is dramatically altered during tumorigenesis...

  5. About the principles of radiation level normalization

    International Nuclear Information System (INIS)

    Nosovskij, A.V.

    2000-01-01

    The paper highlights the impact being made by the radiation level normalization principles upon the social and economic indicators. The newly introduced radiation safety standards - 97 are taken as an example. It is emphasized that it is necessary to use a sound approach while defining radiation protection standards, taking into consideration economic and social factors existing in Ukraine at the moment. Based on the concept of the natural radiation background and available results of the epidemiological surveys, the dose limits are proposed for the radiation protection standards. The paper gives a description of the dose limitation system recommended by the International Committee for Radiation Protection. The paper highlights a negative impact of the line non threshold concept, lack of special knowledge in the medical service and mass media to make decisions to protect people who suffered from the Chernobyl accident

  6. Smoking is associated with increased levels of extracellular peptidylarginine deiminase 2 (PAD2) in the lungs

    DEFF Research Database (Denmark)

    Damgaard, Dres; Friberg Bruun Nielsen, Michael; Quisgaard Gaunsbaek, Maria

    2015-01-01

    lavage (BAL) fluid from smokers, but intracellularly located PAD cannot be responsible for citrullination of extracellular self-antigens. We aimed to establish a link between smoking and extracellular PAD2 in the lungs. METHODS: BAL fluid samples were obtained from 13 smokers and 11 nonsmoking controls...... fluids from smokers as compared to non-smokers (p=0.018). The PAD2 content correlated with the overall CRP levels (p=0.009) and cell count (p=0.016). CONCLUSIONS: This first demonstration of increased levels of extracellular PAD2 in the lungs of smokers supports the hypothesis that smoking promotes...

  7. Increased level of extracellular ATP at tumor sites: in vivo imaging with plasma membrane luciferase.

    Directory of Open Access Journals (Sweden)

    Patrizia Pellegatti

    2008-07-01

    Full Text Available There is growing awareness that tumour cells build up a "self-advantageous" microenvironment that reduces effectiveness of anti-tumour immune response. While many different immunosuppressive mechanisms are likely to come into play, recent evidence suggests that extracellular adenosine acting at A2A receptors may have a major role in down-modulating the immune response as cancerous tissues contain elevated levels of adenosine and adenosine break-down products. While there is no doubt that all cells possess plasma membrane adenosine transporters that mediate adenosine uptake and may also allow its release, it is now clear that most of extracellularly-generated adenosine originates from the catabolism of extracellular ATP.Measurement of extracellular ATP is generally performed in cell supernatants by HPLC or soluble luciferin-luciferase assay, thus it generally turns out to be laborious and inaccurate. We have engineered a chimeric plasma membrane-targeted luciferase that allows in vivo real-time imaging of extracellular ATP. With this novel probe we have measured the ATP concentration within the tumour microenvironment of several experimentally-induced tumours.Our results show that ATP in the tumour interstitium is in the hundreds micromolar range, while it is basically undetectable in healthy tissues. Here we show that a chimeric plasma membrane-targeted luciferase allows in vivo detection of high extracellular ATP concentration at tumour sites. On the contrary, tumour-free tissues show undetectable extracellular ATP levels. Extracellular ATP may be crucial for the tumour not only as a stimulus for growth but also as a source of an immunosuppressive agent such as adenosine. Our approach offers a new tool for the investigation of the biochemical composition of tumour milieu and for development of novel therapies based on the modulation of extracellular purine-based signalling.

  8. Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis.

    Science.gov (United States)

    Waern, Ida; Karlsson, Iulia; Thorpe, Michael; Schlenner, Susan M; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Åbrink, Magnus; Hellman, Lars; Pejler, Gunnar; Wernersson, Sara

    2012-12-01

    Mast cell (MC) granules contain large amounts of proteases of the chymase, tryptase and carboxypeptidase A (MC-CPA) type that are stored in complex with serglycin,a proteoglycan with heparin side chains. Hence, serglycinprotease complexes are released upon MC degranulation and may influence local inflammation. Here we explored the possibility that a serglycin-protease axis may regulate levels of IL-13, a cytokine involved in allergic asthma. Indeed, we found that wild-type MCs efficiently degraded exogenous or endogenously produced IL-13 upon degranulation,whereas serglycin −/− MCs completely lacked this ability.Moreover, MC-mediated IL-13 degradation was blocked both by a serine protease inhibitor and by a heparin antagonist,which suggests that IL-13 degradation is catalyzed by serglycin-dependent serine proteases and that optimal IL-13 degradation is dependent on both the serglycin and the protease component of the serglycin-protease complex.Moreover, IL-13 degradation was abrogated in MC-CPA −/−MC cultures, but was normal in cultures of MCs with an inactivating mutation of MC-CPA, which suggests that the IL-13-degrading serine proteases rely on MC-CPA protein.Together, our data implicate a serglycin-serine protease axis in the regulation of extracellular levels of IL-13. Reduction of IL-13 levels through this mechanism possibly can provide a protective function in the context of allergic inflammation.

  9. Elevation of extracellular adenosine enhances haemopoiesis-stimulating effects of G-CSF in normal and gamma-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Hofer, M.; Pospisil, M.; Netikiva, J.; Hola, J. [Institute of Biophysics, Academy of Sciences of the Czech Republic (Czech Republic)

    1997-03-01

    Effects of combined treatment with drugs elevating extracellular adenosine (dipyridamole /DP/, inhibiting the extracellular uptake of adenosine, and adenosine monophosphate /AMP/, an adenosine pro-drug), and G-CSF (granulocyte colony-stimulating factor) on haemopoiesis of normal and gamma-irradiated mice were ascertained. The agents were administered alone or in combination in a 4-day regimen. In normal, unirradiated animals, the haematological endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, i.e., increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC) and morphologically recognizable granulocyte cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of DP plus AMP administrated 30 minutes before G-CSF. Furthermore, it was found that the stimulatory action of DP plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 {mu}g/d). In experiments with irradiated mice, when the 4-day therapeutic regimen was applied on days 3 to 6 following irradiation with the dose of 4 Gy, analogical stimulation of granulopoiesis was observed in the recovery phase on days 14 and 18 after irradiation. As example, see Fig. 1 for counts of granulocyte cells in femoral bone marrow. (authors)

  10. Elevation of extracellular adenosine enhances haemopoiesis-stimulating effects of G-CSF in normal and gamma-irradiated mice

    International Nuclear Information System (INIS)

    Hofer, M.; Pospisil, M.; Netikiva, J.; Hola, J.

    1997-01-01

    Effects of combined treatment with drugs elevating extracellular adenosine (dipyridamole /DP/, inhibiting the extracellular uptake of adenosine, and adenosine monophosphate /AMP/, an adenosine pro-drug), and G-CSF (granulocyte colony-stimulating factor) on haemopoiesis of normal and gamma-irradiated mice were ascertained. The agents were administered alone or in combination in a 4-day regimen. In normal, unirradiated animals, the haematological endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, i.e., increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC) and morphologically recognizable granulocyte cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of DP plus AMP administrated 30 minutes before G-CSF. Furthermore, it was found that the stimulatory action of DP plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 μg/d). In experiments with irradiated mice, when the 4-day therapeutic regimen was applied on days 3 to 6 following irradiation with the dose of 4 Gy, analogical stimulation of granulopoiesis was observed in the recovery phase on days 14 and 18 after irradiation. As example, see Fig. 1 for counts of granulocyte cells in femoral bone marrow. (authors)

  11. Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

    International Nuclear Information System (INIS)

    Zou, Yani; Leu, David; Chui, Jennifer; Fike, John R.; Huang, Ting-Ting

    2013-01-01

    Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted

  12. Intra-operative on-line discrimination of kidney cancer from normal tissue by IR ATR spectroscopy of extracellular fluid

    Science.gov (United States)

    Urboniene, V.; Velicka, M.; Ceponkus, J.; Pucetaite, M.; Jankevicius, F.; Sablinskas, V.; Steiner, G.

    2016-03-01

    Determination of cancerous and normal kidney tissues during partial, simple or radical nephrectomy surgery was performed by using differences in the IR absorption spectra of extracellular fluid taken from the corresponding tissue areas. The samples were prepared by stamping of the kidney tissue on ATR diamond crystal. The spectral measurements were performed directly in the OR during surgery for 58 patients. It was found that intensities of characteristic spectral bands of glycogen (880-1200 cm-1) in extracellular fluid are sensitive to the type of the tissue and can be used as spectral markers of tumours. Characteristic spectral band of lactic acid (1730 cm-1) - product of the anaerobic glycolysis, taking place in the cancer cells is not suitable for use as a spectral marker of cancerous tissue, since it overlaps with the band of carbonyl stretch in phospholipids and fatty acids. Results of hierarchical cluster analysis of the spectra show that the spectra of healthy and tumour tissue films can be reliably separated into two groups. On the other hand, possibility to differentiate between tumours of different types and grades remains in question. While the fluid from highly malignant G3 tumour tissue contains highly pronounced glycogen spectral bands and can be well separated from benign and G1 tumours by principal component analysis, the variations between spectra from sample to sample prevent from obtaining conclusive results about the grouping between different tumour types and grades. The proposed method is instant and can be used in situ and even in vivo.

  13. Alterations in brain extracellular dopamine and glycine levels following combined administration of the glycine transporter type-1 inhibitor Org-24461 and risperidone.

    Science.gov (United States)

    Nagy, Katalin; Marko, Bernadett; Zsilla, Gabriella; Matyus, Peter; Pallagi, Katalin; Szabo, Geza; Juranyi, Zsolt; Barkoczy, Jozsef; Levay, Gyorgy; Harsing, Laszlo G

    2010-12-01

    The most dominant hypotheses for the pathogenesis of schizophrenia have focused primarily upon hyperfunctional dopaminergic and hypofunctional glutamatergic neurotransmission in the central nervous system. The therapeutic efficacy of all atypical antipsychotics is explained in part by antagonism of the dopaminergic neurotransmission, mainly by blockade of D(2) dopamine receptors. N-methyl-D-aspartate (NMDA) receptor hypofunction in schizophrenia can be reversed by glycine transporter type-1 (GlyT-1) inhibitors, which regulate glycine concentrations at the vicinity of NMDA receptors. Combined drug administration with D(2) dopamine receptor blockade and activation of hypofunctional NMDA receptors may be needed for a more effective treatment of positive and negative symptoms and the accompanied cognitive deficit in schizophrenia. To investigate this type of combined drug administration, rats were treated with the atypical antipsychotic risperidone together with the GlyT-1 inhibitor Org-24461. Brain microdialysis was applied in the striatum of conscious rats and determinations of extracellular dopamine, DOPAC, HVA, glycine, glutamate, and serine concentrations were carried out using HPLC/electrochemistry. Risperidone increased extracellular concentrations of dopamine but failed to influence those of glycine or glutamate measured in microdialysis samples. Org-24461 injection reduced extracellular dopamine concentrations and elevated extracellular glycine levels but the concentrations of serine and glutamate were not changed. When risperidone and Org-24461 were added in combination, a decrease in extracellular dopamine concentrations was accompanied with sustained elevation of extracellular glycine levels. Interestingly, the extracellular concentrations of glutamate were also enhanced. Our data indicate that coadministration of an antipsychotic with a GlyT-1 inhibitor may normalize hypofunctional NMDA receptor-mediated glutamatergic neurotransmission with reduced

  14. Ceftriaxone attenuates ethanol drinking and restores extracellular glutamate concentration through normalization of GLT-1 in nucleus accumbens of male alcohol-preferring rats.

    Science.gov (United States)

    Das, Sujan C; Yamamoto, Bryan K; Hristov, Alexandar M; Sari, Youssef

    2015-10-01

    Alteration of glutamatergic-neurotransmission is a hallmark of alcohol dependence. We have previously reported that chronic ethanol-drinking downregulated glutamate transporter 1 (GLT-1) in nucleus accumbens (NAc) in male P rats in a manner that was reversed by ceftriaxone treatment. However, the effect of ceftriaxone on extracellular glutamate concentrations in NAc after chronic ethanol-drinking has not yet been studied. In the present study, male P rats were treated with ceftriaxone (100 mg/kg/day, i.p.) for five consecutive days following five-weeks of free choice ethanol (15% and 30%) drinking. In vivo microdialysis was performed to measure the extracellular glutamate concentrations in NAc and the effect of blockade of GLT-1 with dihydrokainic acid (DHK) on extracellular glutamate in NAc of ceftriaxone-treated rats was determined. Ceftriaxone treatment attenuated ethanol intake as well as ethanol preference. Extracellular glutamate was significantly higher in NAc after five-weeks of ethanol drinking in saline-treated compared to water control rats. Ceftriaxone treatment blocked the increase extracellular glutamate produced by ethanol intake. Blockade of GLT-1 by DHK reversed the effects of ceftriaxone on glutamate and implicated the role of GLT-1 in the normalization of extracellular glutamate by ceftriaxone. In addition, GLT-1 protein was decreased in ethanol exposed animals and ceftriaxone treatment reversed this deficit. Ceftriaxone treatment also increased glutamine synthetase activity in NAc but not in PFC as compared to ethanol drinking saline-treated rats. Our present study demonstrates that ceftriaxone treatment prevents ethanol drinking in part through normalization of extracellular glutamate concentrations in NAc of male P rats via GLT-1. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Neuropeptide Y infusion into the shell region of the rat nucleus accumbens increases extracellular levels of dopamine

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Wegener, Gregers; Hasselstrøm, Jørgen

    2009-01-01

    Increases in extracellular dopamine in the shell region of the nucleus accumbens are centrally involved in mediating reinforcement of addictive drugs. Neuropeptide Y (NPY) and its receptors are present in the nucleus accumbens and have been implicated in addiction mechanisms. This study further...... explored the potential role of NPY in addiction mechanisms using microdialysis to measure extracellular dopamine in vivo after infusion of NPY directly into the accumbal shell region of adult rats. NPY was found to dose-dependently increase extracellular dopamine levels, indicating that NPY could play...... an important role in drug reinforcement by modulating accumbal dopamine levels...

  16. Bartter Syndrome with Normal Aldosterone Level: An Unusual Presentation.

    Science.gov (United States)

    Huque, S S; Rahman, M H; Khatun, S

    2016-04-01

    Bartter syndrome (BS) is a hereditary disease, with an autosomal recessive or autosomal dominant mode of transmission. It is characterized by salt wasting hypochloraemic, hypokalaemic metabolic alkalosis and hyperreninaemia with normal blood pressure. The primary defect is in the thick ascending limb of loop of Henle (TAL). Herein, we report a case that had typical features of BS like severe dehydration, severe hypokalaemia, metabolic alkalosis and failure to thrive but had normal aldosterone level which is very uncommon.

  17. Ethanol drinking reduces extracellular dopamine levels in the posterior ventral tegmental area of nondependent alcohol-preferring rats.

    Science.gov (United States)

    Engleman, Eric A; Keen, Elizabeth J; Tilford, Sydney S; Thielen, Richard J; Morzorati, Sandra L

    2011-09-01

    Moderate ethanol exposure produces neuroadaptive changes in the mesocorticolimbic dopamine (DA) system in nondependent rats and increases measures of DA neuronal activity in vitro and in vivo. Moreover, moderate ethanol drinking and moderate systemic exposure elevates extracellular DA levels in mesocorticolimbic projection regions. However, the neuroadaptive changes subsequent to moderate ethanol drinking on basal DA levels have not been investigated in the ventral tegmental area (VTA). In the present study, adult female alcohol-preferring (P) rats were divided into alcohol-naive, alcohol-drinking, and alcohol-deprived groups. The alcohol-drinking group had continuous access to water and ethanol (15%, vol/vol) for 8 weeks. The alcohol-deprived group had 6 weeks of access followed by 2 weeks of ethanol deprivation, 2 weeks of ethanol re-exposure, followed again by 2 weeks of deprivation. The deprived rats demonstrated a robust alcohol deprivation effect (ADE) on ethanol reinstatement. The alcohol-naïve group had continuous access to water only. In the last week of the drinking protocol, all rats were implanted with unilateral microdialysis probes aimed at the posterior VTA and no-net-flux microdialysis was conducted to quantify extracellular DA levels and DA clearance. Results yielded significantly lower basal extracellular DA concentrations in the posterior VTA of the alcohol-drinking group compared with the alcohol-naive and alcohol-deprived groups (3.8±0.3nM vs. 5.0±0.5nM [Palcohol-drinking and alcohol-naive groups (72±2% vs. 46±4%, respectively) and not significantly different (P=.051) between alcohol-deprived and alcohol-naive groups (61±6% for the alcohol-deprived group). The data indicate that reductions in basal DA levels within the posterior VTA occur after moderate chronic ethanol intake in nondependent P rats. This reduction may result, in part, from increased DA uptake and may be important for the maintenance of ethanol drinking. These adaptations

  18. NORMAL NASAL GENE EXPRESSION LEVELS USING CDNA ARRAY TECHNOLOGY

    Science.gov (United States)

    Normal Nasal Gene Expression Levels Using cDNA Array Technology. The nasal epithelium is a target site for chemically-induced toxicity and carcinogenicity. To detect and analyze genetic events which contribute to nasal tumor development, we first defined the gene expressi...

  19. Extracellular Zn2+ Is Essential for Amyloid β1-42-Induced Cognitive Decline in the Normal Brain and Its Rescue.

    Science.gov (United States)

    Takeda, Atsushi; Tamano, Haruna; Tempaku, Munekazu; Sasaki, Miku; Uematsu, Chihiro; Sato, Shoko; Kanazawa, Hiroaki; Datki, Zsolt L; Adlard, Paul A; Bush, Ashley I

    2017-07-26

    Brain Aβ 1-42 accumulation is considered an upstream event in pathogenesis of Alzheimer's disease. However, accumulating evidence indicates that other neurochemical changes potentiate the toxicity of this constitutively generated peptide. Here we report that the interaction of Aβ 1-42 with extracellular Zn 2+ is essential for in vivo rapid uptake of Aβ 1-42 and Zn 2+ into dentate granule cells in the normal rat hippocampus. The uptake of both Aβ 1-42 and Zn 2+ was blocked by CaEDTA, an extracellular Zn 2+ chelator, and by Cd 2+ , a metal that displaces Zn 2+ for Aβ 1-42 binding. In vivo perforant pathway LTP was unaffected by perfusion with 1000 nm Aβ 1-42 in ACSF without Zn 2+ However, LTP was attenuated under preperfusion with 5 nm Aβ 1-42 in ACSF containing 10 nm Zn 2+ , recapitulating the concentration of extracellular Zn 2+ , but not with 5 nm Aβ 1-40 in ACSF containing 10 nm Zn 2+ Aβ 1-40 and Zn 2+ were not taken up into dentate granule cells under these conditions, consistent with lower affinity of Aβ 1-40 for Zn 2+ than Aβ 1-42 Aβ 1-42 -induced attenuation of LTP was rescued by both CaEDTA and CdCl 2 , and was observed even with 500 pm Aβ 1-42 Aβ 1-42 injected into the dentate granule cell layer of rats induced a rapid memory disturbance that was also rescued by coinjection of CdCl 2 The present study supports blocking the formation of Zn-Aβ 1-42 in the extracellular compartment as an effective preventive strategy for Alzheimer's disease. SIGNIFICANCE STATEMENT Short-term memory loss occurs in normal elderly and increases in the predementia stage of Alzheimer's disease (AD). Amyloid-β 1-42 (Aβ 1-42 ), a possible causing peptide in AD, is bound to Zn 2+ in the extracellular compartment in the hippocampus induced short-term memory loss in the normal rat brain, suggesting that extracellular Zn 2+ is essential for Aβ 1-42 -induced short-term memory loss. The evidence is important to find an effective preventive strategy for AD, which is

  20. Characterization of rat primary trigeminal satellite glial cells and associated extracellular vesicles under normal and inflammatory conditions

    DEFF Research Database (Denmark)

    Vinterhøj, Hye Sook Han; Stensballe, Allan; Duroux, Meg

    2018-01-01

    Satellite glial cells (SGCs) in sensory ganglia contribute to the pathogenesis of chronic pain, potentially through mediating extracellular or paracrine signaling. Recently, extracellular vesicles (EVs) in the form of exosomes have been found to play an important role in cell-cell communication....... Results demonstrated that SGCs shed vesicles in the size range of exosomes (>150 nm) but with altered protein expression upon LPS-activation. Proteomic profiling of SGCs-shed EVs showed that a number of proteins were differentially regulated upon LPS stimulation such as junction plakoglobin and myosin 9...

  1. Extracellular levels of lactate, but not oxygen, reflect sleep homeostasis in the rat cerebral cortex.

    Science.gov (United States)

    Dash, Michael B; Tononi, Giulio; Cirelli, Chiara

    2012-07-01

    It is well established that brain metabolism is higher during wake and rapid eye movement (REM) sleep than in nonrapid eye movement (NREM) sleep. Most of the brain's energy is used to maintain neuronal firing and glutamatergic transmission. Recent evidence shows that cortical firing rates, extracellular glutamate levels, and markers of excitatory synaptic strength increase with time spent awake and decline throughout NREM sleep. These data imply that the metabolic cost of each behavioral state is not fixed but may reflect sleep-wake history, a possibility that is investigated in the current report. Chronic (4d) electroencephalographic (EEG) recordings in the rat cerebral cortex were coupled with fixed-potential amperometry to monitor the extracellular concentration of oxygen ([oxy]) and lactate ([lac]) on a second-by-second basis across the spontaneous sleep-wake cycle and in response to sleep deprivation. Basic sleep research laboratory. Wistar Kyoto (WKY) adult male rats. N/A. Within 30-60 sec [lac] and [oxy] progressively increased during wake and REM sleep and declined during NREM sleep (n = 10 rats/metabolite), but with several differences. [Oxy], but not [lac], increased more during wake with high motor activity and/or elevated EEG high-frequency power. Meanwhile, only the NREM decline of [lac] reflected sleep pressure as measured by slow-wave activity, mirroring previous results for cortical glutamate. The observed state-dependent changes in cortical [lac] and [oxy] are consistent with higher brain metabolism during waking and REM sleep in comparison with NREM sleep. Moreover, these data suggest that glycolytic activity, most likely through its link with glutamatergic transmission, reflects sleep homeostasis.

  2. Suramin Inhibits Osteoarthritic Cartilage Degradation by Increasing Extracellular Levels of Chondroprotective Tissue Inhibitor of Metalloproteinases 3.

    Science.gov (United States)

    Chanalaris, Anastasios; Doherty, Christine; Marsden, Brian D; Bambridge, Gabriel; Wren, Stephen P; Nagase, Hideaki; Troeberg, Linda

    2017-10-01

    Osteoarthritis is a common degenerative joint disease for which no disease-modifying drugs are currently available. Attempts to treat the disease with small molecule inhibitors of the metalloproteinases that degrade the cartilage matrix have been hampered by a lack of specificity. We aimed to inhibit cartilage degradation by augmenting levels of the endogenous metalloproteinase inhibitor, tissue inhibitor of metalloproteinases (TIMP)-3, through blocking its interaction with the endocytic scavenger receptor, low-density lipoprotein receptor-related protein 1 (LRP1). We discovered that suramin (C 51 H 40 N 6 O 23 S 6 ) bound to TIMP-3 with a K D value of 1.9 ± 0.2 nM and inhibited its endocytosis via LRP1, thus increasing extracellular levels of TIMP-3 and inhibiting cartilage degradation by the TIMP-3 target enzyme, adamalysin-like metalloproteinase with thrombospondin motifs 5. NF279 (8,8'-[carbonyl bis (imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)] bis -1,3,5-naphthalenetrisulfonic acid hexasodium salt), a structural analog of suramin, has an increased affinity for TIMP-3 and increased ability to inhibit TIMP-3 endocytosis and protect cartilage. Suramin is thus a promising scaffold for the development of novel therapeutics to increase TIMP-3 levels and inhibit cartilage degradation in osteoarthritis. Copyright © 2017 by The Author(s).

  3. LRRK2 affects vesicle trafficking, neurotransmitter extracellular level and membrane receptor localization.

    Directory of Open Access Journals (Sweden)

    Rossana Migheli

    Full Text Available The leucine-rich repeat kinase 2 (LRRK2 gene was found to play a role in the pathogenesis of both familial and sporadic Parkinson's disease (PD. LRRK2 encodes a large multi-domain protein that is expressed in different tissues. To date, the physiological and pathological functions of LRRK2 are not clearly defined. In this study we have explored the role of LRRK2 in controlling vesicle trafficking in different cellular or animal models and using various readouts. In neuronal cells, the presence of LRRK2(G2019S pathological mutant determines increased extracellular dopamine levels either under basal conditions or upon nicotine stimulation. Moreover, mutant LRRK2 affects the levels of dopamine receptor D1 on the membrane surface in neuronal cells or animal models. Ultrastructural analysis of PC12-derived cells expressing mutant LRRK2(G2019S shows an altered intracellular vesicle distribution. Taken together, our results point to the key role of LRRK2 to control vesicle trafficking in neuronal cells.

  4. Extracellular DNA amplicon sequencing reveals high levels of benthic eukaryotic diversity in the central Red Sea

    KAUST Repository

    Pearman, John K.

    2015-11-01

    The present study aims to characterize the benthic eukaryotic biodiversity patterns at a coarse taxonomic level in three areas of the central Red Sea (a lagoon, an offshore area in Thuwal and a shallow coastal area near Jeddah) based on extracellular DNA. High-throughput amplicon sequencing targeting the V9 region of the 18S rRNA gene was undertaken for 32 sediment samples. High levels of alpha-diversity were detected with 16,089 operational taxonomic units (OTUs) being identified. The majority of the OTUs were assigned to Metazoa (29.2%), Alveolata (22.4%) and Stramenopiles (17.8%). Stramenopiles (Diatomea) and Alveolata (Ciliophora) were frequent in a lagoon and in shallower coastal stations, whereas metazoans (Arthropoda: Maxillopoda) were dominant in deeper offshore stations. Only 24.6% of total OTUs were shared among all areas. Beta-diversity was generally lower between the lagoon and Jeddah (nearshore) than between either of those and the offshore area, suggesting a nearshore–offshore biodiversity gradient. The current approach allowed for a broad-range of benthic eukaryotic biodiversity to be analysed with significantly less labour than would be required by other traditional taxonomic approaches. Our findings suggest that next generation sequencing techniques have the potential to provide a fast and standardised screening of benthic biodiversity at large spatial and temporal scales.

  5. Circulating Levels of Irisin in Hypopituitary and Normal Subjects.

    Directory of Open Access Journals (Sweden)

    Lara Pena-Bello

    Full Text Available The recently identified myokine irisin conveys some of the benefits of exercise. Hypopituitarism with adult growth hormone deficiency (HP is a situation characterized by decreased GH secretion and an altered body composition.Our aim was to study the skeletal muscle hormone irisin in HP, and compare the results with a similar group of normal subjects.Seventeen HP patients and fifty-one normal subjects of similar age and sex were studied. The diagnosis of GH deficiency was confirmed by the presence of pituitary disease and a peak GH secretion below 3 μg/L after an insulin tolerance test. The patients were adequately treated for all pituitary hormone deficits, except for GH. Fasting serum irisin was measured with an enzyme immunoassay, and HOMA-IR, QUICKI and HOMA-β were calculated.Fasting irisin levels (ng/ml were similar in normal [208.42 (168.44-249.23] and HP patients [195.13 (178.44-241.44]. In the control group there were moderate significant positive correlations between irisin and BMI, waist circumference, leptin, fasting insulin, HOMA-IR, HOMA-β, triglycerides, and cholesterol. In the control group there were moderate significant negative correlations between irisin and IGF-I and QUICKI. In the hypopituitary group there were moderate significant positive correlations between irisin and body fat and HOMA-β.We found similar irisin levels in GH deficiency hypopituitary patients when compared with normal subjects. The correlation between irisin and adiposity related factors suggests that that in the case of this clinical model, irisin is regulated by adiposity and not by GH.

  6. Serum gastrin level in pregnancy running a normal course

    Energy Technology Data Exchange (ETDEWEB)

    Milev, N; Todorov, G; Pumpalov, A; Ignatov, A [Meditsinska Akademiya, Sofia (Bulgaria). Nauchen Inst. po Rentgenologiya i Radiobiologiya

    1982-01-01

    The serum gastrin level (SGL) is studied in dynamics during each lunar month of pregnancy in order to accumulate data which may serve the purpose of a tentative standard for serum gastrin level in this peculiar physiologic condition. A group of 110 pregnant women with a normal development of pregnancy, as documented by the clinical and paraclinical examination, are covered by the study. Blood samples are taken before meal, and a radioimmunologic method is used for SGL assessment. The number of women analyzed and the mean age by lunar months are shown. The normal value established in nonpregnant women of the same age group is 28+-7 mg/ml, relative to which the average values during the first five i.m. do not show statistically significant differences. During the 6th l.m. SGL increases to 68.5 mg/ml, while after the 7th l.m. values are recorded exceeding 1aa mg/ml with a maximum observed in the 8th and 9th l.m. The mechanisms eventually involved in the occurrence of gastrinemia during the second half of pregnancy are discussed, e.g. 1/mechanical compression of the stomach by the progressively growing uterus, 2/decreased breakdown, inhibition and elimimation of the hormone by the kidneys, and 3/possible correlative dependence between changes in SGL and changes in the level of hormones playing a predominant role in the hormonal status after the fifth month of pregnancy.

  7. Study of plasma adrenomedullin level in normal pregnancy and preclampsia.

    Science.gov (United States)

    Senna, Azza Abo; Zedan, Magda; el-Salam, Gamal E Abd; el-Mashad, Ashraf I

    2008-02-06

    The aim of this study was to evaluate whether maternal circulating adrenomedullin (AM) values in patients with preeclampsia are different from those in normotensive pregnant women at different gestational ages. In a prospective clinical study, 90 women aged 17 to 40 years old, were divided into 4 main groups: group I (45 women): Normotensive pregnant women at first trimester (15 women), second trimester (15 women), and third trimester (15 women) of pregnancies. Group II (15 women): Pregnant women with preeclampsia at 25 to 38 weeks of gestation. Group III (15 women): Normotensive healthy nonpregnant women. Group IV (15 women): Hypertensive nonpregnant women. The plasma AM concentration was measured in all women by using enzyme immunoassay kits. Plasma AM levels in pregnant women with normal blood pressure at different gestational ages (first, second, and third trimesters) were statistically significantly higher than those detected in nonpregnant normotensive women and significantly increased with increasing gestational age (P < .001). Moreover, there was significant positive correlation between plasma AM levels and increasing gestational age (r = 0.915, P < .001). Preeclamptic patients had the highest mean plasma AM levels compared with all other groups, which is statistically significant (P < .001) and there was a significant positive correlation between plasma AM levels and systolic blood pressure, diastolic blood pressure, severity of preeclampsia, and proteinuria in pregnant patients with preeclampsia. Maternal plasma AM concentration increases throughout pregnancy and increases as gestational age progresses. AM production starts very early in gestation, suggesting that it may have an important role in human reproduction, from implantation to delivery. Maternal plasma AM level in preeclampsia appears to be higher than that in normal pregnancy.

  8. Extracellular signal-regulated kinase 1 and 2 are not required for GnRH neuron development and normal female reproductive axis function in mice.

    Science.gov (United States)

    Wierman, Margaret E; Xu, Mei; Pierce, A; Bliesner, B; Bliss, S P; Roberson, M S

    2012-01-01

    Selective deletion of extracellular signal-regulated kinase (ERK) 1 and ERK2 in the pituitary gonadotrope and ovarian granulosa cells disrupts female reproductive axis function. Thus, we asked if ERK1 and ERK2 are critical for GnRH neuron ontogeny or the central control of female reproductive function. GnRH-Cre-recombinase (Cre+) expressing mice were crossed with mice with a global deletion of ERK1 and a floxed ERK2 allele (Erk1-/Erk2fl/fl) to selectively delete ERK2 in GnRH neurons. Cre-recombinase mRNA was selectively expressed in the brain of Cre+ mice. GnRH neuron number and location were determined during embryogenesis and in the adult. GnRH neuron counts at E15 did not differ between experimental and control groups (1,198 ± 65 and 1,160 ± 80 respectively, p = NS). In adults, numbers of GnRH neurons in the GnRHCre+Erk1-/Erk2- mice (741 ± 157) were similar to those in controls (756 ± 7), without alteration in their distribution across the forebrain. ERK1 and 2 deficiency did not alter the timing of vaginal opening, age at first estrus, or estrous cyclicity. Although ERK1 and 2 are components of a dominant signaling pathway in GnRH neuronal cells that modulates survival and control of GnRH gene expression, other signaling pathways compensate for their deletion in vivo to allow GnRH neuron survival and targeting and normal onset of female sexual maturation and reproductive function. In contrast to effects at the pituitary and the ovary, ERK1 and ERK2 are dispensable at the level of the GnRH neuron. Copyright © 2011 S. Karger AG, Basel.

  9. Normalization at the field level: fractional counting of citations

    OpenAIRE

    Leydesdorff, Loet; Opthof, Tobias

    2010-01-01

    Van Raan et al. (2010; arXiv:1003.2113) have proposed a new indicator (MNCS) for field normalization. Since field normalization is also used in the Leiden Rankings of universities, we elaborate our critique of journal normalization in Opthof & Leydesdorff (2010; arXiv:1002.2769) in this rejoinder concerning field normalization. Fractional citation counting thoroughly solves the issue of normalization for differences in citation behavior among fields. This indicator can also be used to obtain ...

  10. Normal levels of anticoagulant heparan sulfate are not essential for normal hemostasis

    Science.gov (United States)

    HajMohammadi, Sassan; Enjyoji, Keiichi; Princivalle, Marc; Christi, Patricia; Lech, Miroslav; Beeler, David; Rayburn, Helen; Schwartz, John J.; Barzegar, Samad; de Agostini, Ariane I.; Post, Mark J.; Rosenberg, Robert D.; Shworak, Nicholas W.

    2003-01-01

    Endothelial cell production of anticoagulant heparan sulfate (HSact) is controlled by the Hs3st1 gene, which encodes the rate-limiting enzyme heparan sulfate 3-O-sulfotransferase-1 (3-OST-1). In vitro, HSact dramatically enhances the neutralization of coagulation proteases by antithrombin. The in vivo role of HSact was evaluated by generating Hs3st1–/– knockout mice. Hs3st1–/– animals were devoid of 3-OST-1 enzyme activity in plasma and tissue extracts. Nulls showed dramatic reductions in tissue levels of HSact but maintained wild-type levels of tissue fibrin accumulation under both normoxic and hypoxic conditions. Given that vascular HSact predominantly occurs in the subendothelial matrix, mice were subjected to a carotid artery injury assay in which ferric chloride administration induces de-endothelialization and occlusive thrombosis. Hs3st1–/– and Hs3st1+/+ mice yielded indistinguishable occlusion times and comparable levels of thrombin•antithrombin complexes. Thus, Hs3st1–/– mice did not show an obvious procoagulant phenotype. Instead, Hs3st1–/– mice exhibited genetic background–specific lethality and intrauterine growth retardation, without evidence of a gross coagulopathy. Our results demonstrate that the 3-OST-1 enzyme produces the majority of tissue HSact. Surprisingly, this bulk of HSact is not essential for normal hemostasis in mice. Instead, 3-OST-1–deficient mice exhibited unanticipated phenotypes suggesting that HSact or additional 3-OST-1–derived structures may serve alternate biologic roles. PMID:12671048

  11. The role of the extracellular matrix in tissue distribution of macromolecules in normal and pathological tissues: potential therapeutic consequences.

    Science.gov (United States)

    Wiig, Helge; Gyenge, Christina; Iversen, Per Ole; Gullberg, Donald; Tenstad, Olav

    2008-05-01

    The interstitial space is a dynamic microenvironment that consists of interstitial fluid and structural molecules of the extracellular matrix, such as glycosaminoglycans (hyaluronan and proteoglycans) and collagen. Macromolecules can distribute in the interstitium only in those spaces unoccupied by structural components, a phenomenon called interstitial exclusion. The exclusion phenomenon has direct consequences for plasma volume regulation. Early studies have assigned a major role to collagen as an excluding agent that accounts for the sterical (geometrical) exclusion. More recently, it has been shown that the contribution of negatively charged glycosaminoglycans might also be significant, resulting in an additional electrostatical exclusion effect. This charge effect may be of importance for drug uptake and suggests that either the glycosaminoglycans or the net charge of macromolecular substances to be delivered may be targeted to increase the available volume and uptake of macromolecular therapeutic agents in tumor tissue. Here, we provide an overview of the structural components of the interstitium and discuss the importance the sterical and electrostatical components have on the dynamics of transcapillary fluid exchange.

  12. Dopamine D1 receptor-dependent regulation of extracellular citrulline level in the rat nucleus accumbens during conditioned fear response.

    Science.gov (United States)

    Saulskaya, Natalia B; Fofonova, Nellia V; Sudorghina, Polina V; Saveliev, Sergey A

    2008-08-01

    Nucleus accumbens (N.Acc) contains a subclass of nitric oxide (NO)-generating interneurons that are presumably regulated by the dopamine input. Receptor mechanisms underlying dopamine-NO interaction in the N.Acc are poorly understood. In the current study, we used in vivo microdialysis combined with high-performance liquid chromatography to examine participation of dopamine D1 receptors in regulation of extracellular levels of citrulline (an NO co-product) in the medial N.Acc of Sprague-Dawley rats during both pharmacological challenge and a conditioned fear response. The intraaccumbal infusion of the D1 receptor agonist SKF-38393 (100-500 microM) increased dose-dependently the local dialysate citrulline levels. The SKF-38393-induced increase in extracellular citrulline was prevented by intraaccumbal infusions of 500 microM 7-nitroindazole, a neuronal NO synthase inhibitor. In behavioral microdialysis experiment, the accumbal levels of extracellular citrulline markedly increased in rats given a mild footshock paired with tone. The presentation of the tone previously paired with footshock (the conditioned fear response) produced a "conditioned" rise of extracellular citrulline levels in the N.Acc which was attenuated by intraaccumbal infusion of 100 microM SCH-23390, a dopamine D1 receptor antagonist, and prevented by intraaccumbal infusion of 500 microM 7-nitroindazole. The results suggest that in the N.Acc, the dopamine D1 receptors might regulate the neuronal NO synthase activity; this dopamine-dependent mechanism seems to participate in activation of the neuronal NO synthase and probably NO formation in this brain area during the conditioned fear response.

  13. Visualizing Tensor Normal Distributions at Multiple Levels of Detail.

    Science.gov (United States)

    Abbasloo, Amin; Wiens, Vitalis; Hermann, Max; Schultz, Thomas

    2016-01-01

    Despite the widely recognized importance of symmetric second order tensor fields in medicine and engineering, the visualization of data uncertainty in tensor fields is still in its infancy. A recently proposed tensorial normal distribution, involving a fourth order covariance tensor, provides a mathematical description of how different aspects of the tensor field, such as trace, anisotropy, or orientation, vary and covary at each point. However, this wealth of information is far too rich for a human analyst to take in at a single glance, and no suitable visualization tools are available. We propose a novel approach that facilitates visual analysis of tensor covariance at multiple levels of detail. We start with a visual abstraction that uses slice views and direct volume rendering to indicate large-scale changes in the covariance structure, and locations with high overall variance. We then provide tools for interactive exploration, making it possible to drill down into different types of variability, such as in shape or orientation. Finally, we allow the analyst to focus on specific locations of the field, and provide tensor glyph animations and overlays that intuitively depict confidence intervals at those points. Our system is demonstrated by investigating the effects of measurement noise on diffusion tensor MRI, and by analyzing two ensembles of stress tensor fields from solid mechanics.

  14. Association of Levels of Antibodies from Patients with Inflammatory Bowel Disease with Extracellular Proteins of Food and Probiotic Bacteria

    Directory of Open Access Journals (Sweden)

    Arancha Hevia

    2014-01-01

    Full Text Available Inflammatory bowel disease (IBD is an autoimmune disease characterized by a chronic inflammation of the gastrointestinal tract mucosa and is related to an abnormal immune response to commensal bacteria. Our aim of the present work has been to explore the levels of antibodies (IgG and IgA raised against extracellular proteins produced by LAB and its association with IBD. We analyzed, by Western-blot and ELISA, the presence of serum antibodies (IgA and IgG developed against extracellular protein fractions produced by different food bacteria from the genera Bifidobacterium and Lactobacillus. We used a sera collection consisting of healthy individuals (HC, n=50, Crohn's disease patients (CD, n=37, and ulcerative colitis patients (UC, n=15. Levels of IgA antibodies developed against a cell-wall hydrolase from Lactobacillus casei subsp. rhamnosus GG (CWH were significantly higher in the IBD group (P<0.002; n=52. The specificity of our measurements was confirmed by measuring IgA antibodies developed against the CWH peptide 365-VNTSNQTAAVSAS-377. IBD patients appeared to have different immune response to food bacteria. This paper sets the basis for developing systems for early detection of IBD, based on the association of high levels of antibodies developed against extracellular proteins from food and probiotic bacteria.

  15. Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

    International Nuclear Information System (INIS)

    Liu, Jing; Parsons, Loren; Pope, Carey

    2013-01-01

    Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF leads to differences in extracellular eCB levels and toxicity. Microdialysis cannulae were implanted into hippocampus of adult male rats followed by treatment with vehicle (peanut oil, 2 ml/kg, sc), PS (27 mg/kg) or CPF (280 mg/kg) 6–7 days later. Signs of toxicity, AChE, FAAH and MAGL inhibition, and extracellular levels of AEA and 2AG were measured 2 and 4 days later. Signs were noted in PS-treated rats but not in controls or CPF-treated rats. Cholinesterase inhibition was extensive in hippocampus with PS (89–90%) and CPF (78–83%) exposure. FAAH activity was also markedly reduced (88–91%) by both OPs at both time-points. MAGL was inhibited by both OPs but to a lesser degree (35–50%). Increases in extracellular AEA levels were noted after either PS (about 2-fold) or CPF (about 3-fold) while lesser treatment-related 2-AG changes were noted. The cannabinoid CB1 receptor antagonist/inverse agonist AM251 (3 mg/kg, ip) had no influence on functional signs after CPF but markedly decreased toxicity in PS-treated rats. The results suggest that extracellular eCBs levels can be markedly elevated by both PS and CPF. CB1-mediated signaling appears to play a role in the acute toxicity of PS but the role of eCBs in CPF toxicity remains unclear. - Highlights: • Chlorpyrifos and parathion both extensively inhibited hippocampal cholinesterase. • Functional signs were only noted with parathion. • Chlorpyrifos and parathion increased hippocampal extracellular anandamide levels. • 2-Arachidonoylglycerol levels were

  16. Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jing [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States); Parsons, Loren [Committee on Neurobiology of Affective Disorders, The Scripps Research Institute, La Jolla, CA (United States); Pope, Carey, E-mail: carey.pope@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States)

    2013-11-01

    Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF leads to differences in extracellular eCB levels and toxicity. Microdialysis cannulae were implanted into hippocampus of adult male rats followed by treatment with vehicle (peanut oil, 2 ml/kg, sc), PS (27 mg/kg) or CPF (280 mg/kg) 6–7 days later. Signs of toxicity, AChE, FAAH and MAGL inhibition, and extracellular levels of AEA and 2AG were measured 2 and 4 days later. Signs were noted in PS-treated rats but not in controls or CPF-treated rats. Cholinesterase inhibition was extensive in hippocampus with PS (89–90%) and CPF (78–83%) exposure. FAAH activity was also markedly reduced (88–91%) by both OPs at both time-points. MAGL was inhibited by both OPs but to a lesser degree (35–50%). Increases in extracellular AEA levels were noted after either PS (about 2-fold) or CPF (about 3-fold) while lesser treatment-related 2-AG changes were noted. The cannabinoid CB1 receptor antagonist/inverse agonist AM251 (3 mg/kg, ip) had no influence on functional signs after CPF but markedly decreased toxicity in PS-treated rats. The results suggest that extracellular eCBs levels can be markedly elevated by both PS and CPF. CB1-mediated signaling appears to play a role in the acute toxicity of PS but the role of eCBs in CPF toxicity remains unclear. - Highlights: • Chlorpyrifos and parathion both extensively inhibited hippocampal cholinesterase. • Functional signs were only noted with parathion. • Chlorpyrifos and parathion increased hippocampal extracellular anandamide levels. • 2-Arachidonoylglycerol levels were

  17. A human pericardium biopolymeric scaffold for autologous heart valve tissue engineering: cellular and extracellular matrix structure and biomechanical properties in comparison with a normal aortic heart valve.

    Science.gov (United States)

    Straka, Frantisek; Schornik, David; Masin, Jaroslav; Filova, Elena; Mirejovsky, Tomas; Burdikova, Zuzana; Svindrych, Zdenek; Chlup, Hynek; Horny, Lukas; Daniel, Matej; Machac, Jiri; Skibová, Jelena; Pirk, Jan; Bacakova, Lucie

    2018-04-01

    The objective of our study was to compare the cellular and extracellular matrix (ECM) structure and the biomechanical properties of human pericardium (HP) with the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV samples (from 5 patients) were harvested during heart surgery. The main cells in HP were pericardial interstitial cells, which are fibroblast-like cells of mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The ECM of HP had a statistically significantly (p structures of the two tissues, the dense part of fibrous HP (49 ± 2%) and the lamina fibrosa of NAV (47 ± 4%), was similar. In both tissues, the secant elastic modulus (Es) was significantly lower in the transversal direction (p structure and has the biomechanical properties required for a tissue from which an autologous heart valve replacement may be constructed.

  18. 2-deoxyglucose tissue levels and insulin levels following tolazamide dosing in normal and obese mice

    International Nuclear Information System (INIS)

    Skillman, C.A.; Fletcher, H.P.

    1986-01-01

    The effect of tolazamide (TZ), a sulfonylurea, on 14 C-2-deoxyglucose ( 14 C-2DG) tissue distribution and insulin levels of normal and obese mice was investigated using an in vivo physiological method. Acute doses of TZ (50 mg/kg ip) increased 14 C-2DG levels in gastrocnemius muscle and retroperitoneal fat and produced a transient elevation of insulin which most likely accounts for the increased 14 C-2DG levels in muscle and fat. The results demonstrate that the in vivo 14 C-2DG method produced results consistent with known actions of sulfonylureas on in vitro hexose assimilation in muscle and fat. Subchronic treatment (7 days) with TZ 50 mg/kg ip twice daily did not result in increased insulin-stimulated 14 C-2DG tissue levels in normal mice when compared to saline treated controls. However, insulin levels were lower in mice treated subchronically with TZ compared to saline controls suggesting an enhancement of insulin action. Viable yellow obese mice represent a model of maturity onset obesity presenting with insulin resistance. The insulin resistance of this obese strain appears to reside in the fat tissue as assessed by comparing 14 C-2DG tissue levels of obese mice with lean littermate controls. Subchronic TZ treatment had no effect on 14 C-2DG uptake in fat or muscle tissue of viable yellow obese mice and did not alter their plasma insulin levels. It appears that genetically obese viable mice may be resistant to subchronic treatment with TZ. (author)

  19. Increased extracellular dopamine and 5-hydroxytryptamine levels contribute to enhanced subthalamic nucleus neural activity during exhausting exercise

    Directory of Open Access Journals (Sweden)

    Y Hu

    2015-09-01

    Full Text Available The purpose of the study was to explore the mechanism underlying the enhanced subthalamic nucleus (STN neural activity during exhausting exercise from the perspective of monoamine neurotransmitters and changes of their corresponding receptors. Rats were randomly divided into microdialysis and immunohistochemistry study groups. For microdialysis study, extracellular fluid of the STN was continuously collected with a microdialysis probe before, during and 90 min after one bout of exhausting exercise. Dopamine (DA and 5-hydroxytryptamine (5-HT levels were subsequently detected with high-performance liquid chromatography (HPLC. For immunohistochemistry study, the expression of DRD 2 and HT 2C receptors in the STN, before, immediately after and 90 min after exhaustion was detected through immunohistochemistry technique. Microdialysis study results showed that the extracellular DA and 5-HT neurotransmitters increased significantly throughout the procedure of exhausting exercise and the recovery period (P0.05. Our results suggest that the increased extracellular DA and 5-HT in the STN might be one important factor leading to the enhanced STN neural activity and the development of fatigue during exhausting exercise. This study may essentially offer useful evidence for better understanding of the mechanism of the central type of exercise-induced fatigue.

  20. Trichomonas vaginalis NTPDase and ecto-5'-nucleotidase hydrolyze guanine nucleotides and increase extracellular guanosine levels under serum restriction.

    Science.gov (United States)

    Menezes, Camila Braz; Durgante, Juliano; de Oliveira, Rafael Rodrigues; Dos Santos, Victor Hugo Jacks Mendes; Rodrigues, Luiz Frederico; Garcia, Solange Cristina; Dos Santos, Odelta; Tasca, Tiana

    2016-05-01

    Trichomonas vaginalis is the aethiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease in the world. The purinergic signaling pathway is mediated by extracellular nucleotides and nucleosides that are involved in many biological effects as neurotransmission, immunomodulation and inflammation. Extracellular nucleotides can be hydrolyzed by a family of enzymes known as ectonucleotidases including the ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) family which hydrolyses nucleosides triphosphate and diphosphate as preferential substrates and ecto-5'-nucleotidase which catalyzes the conversion of monophosphates into nucleosides. In T. vaginalis the E-NTPDase and ecto-5'-nucleotidase activities upon adenine nucleotides have already been characterized in intact trophozoites but little is known concerning guanine nucleotides and nucleoside. These enzymes may exert a crucial role on nucleoside generation, providing the purine sources for the synthesis de novo of these essential nutrients, sustaining parasite growth and survival. In this study, we investigated the hydrolysis profile of guanine-related nucleotides and nucleoside in intact trophozoites from long-term-grown and fresh clinical isolates of T. vaginalis. Knowing that guanine nucleotides are also substrates for T. vaginalis ectoenzymes, we evaluated the profile of nucleotides consumption and guanosine uptake in trophozoites submitted to a serum limitation condition. Results show that guanine nucleotides (GTP, GDP, GMP) were substrates for T. vaginalis ectonucleotidases, with expected kinetic parameters for this enzyme family. Different T. vaginalis isolates (two from the ATCC and nine fresh clinical isolates) presented a heterogeneous hydrolysis profile. The serum culture condition increased E-NTPDase and ecto-5'-nucleotidase activities with high consumption of extracellular GTP generating enhanced GDP, GMP and guanosine levels as demonstrated by HPLC, with final

  1. Serum levels of growth hormone binding protein in children with normal and precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Fisker, Sidse; Scheike, Thomas Harder

    2000-01-01

    To study the regulation of GHBP serum levels by gonadal steroids in normal and precocious puberty.......To study the regulation of GHBP serum levels by gonadal steroids in normal and precocious puberty....

  2. Modulation of memory with septal injections of morphine and glucose: effects on extracellular glucose levels in the hippocampus.

    Science.gov (United States)

    McNay, Ewan C; Canal, Clinton E; Sherwin, Robert S; Gold, Paul E

    2006-02-28

    The concentration of glucose in the extracellular fluid (ECF) of the hippocampus decreases substantially during memory testing on a hippocampus-dependent memory task. Administration of exogenous glucose, which enhances task performance, prevents this decrease, suggesting a relationship between hippocampal glucose availability and memory performance. In the present experiment, spontaneous alternation performance and task-related changes in hippocampal ECF glucose were assessed in rats after intraseptal administration of morphine, which impairs memory on a spontaneous alternation task, and after co-administration of intraseptal glucose, which attenuates that impairment. Consistent with previous findings, spontaneous alternation testing resulted in a decrease in hippocampal ECF glucose levels in control rats. However, rats that received intraseptal morphine prior to testing showed memory impairments and an absence of the task-related decrease in hippocampal ECF glucose levels. Intraseptal co-administration of glucose with morphine attenuated the memory impairment, and ECF glucose levels in the hippocampus decreased in a manner comparable to that seen in control rats. These data suggest that fluctuations in hippocampal ECF glucose levels may be a marker of mnemonic processing and support the view that decreases in extracellular glucose during memory testing reflect increased glucose demand during memory processing.

  3. High-level extracellular production and characterization of Candida antarctica lipase B in Pichia pastoris.

    Science.gov (United States)

    Eom, Gyeong Tae; Lee, Seung Hwan; Song, Bong Keun; Chung, Keun-Wo; Kim, Young-Wun; Song, Jae Kwang

    2013-08-01

    The gene encoding lipase B from Candida antarctica (CalB) was expressed in Pichia pastoris after it was synthesized by the recursive PCR and cloned into the Pichia expression plasmid, pPICZαA. The CalB was successfully secreted in the recombinant P. pastoris strain X-33 with an apparent molecular weight of 34 kDa. For 140 h flask culture, the dry cell weight and the extracellular lipase activity reached at 5.4 g/l and 57.9 U/l toward p-nitrophenyl palmitate, respectively. When we performed the fed-batch fermentation using a methanol feeding strategy for 110 h, the dry cell weight and the extracellular lipase activity were increased to 135.7 g/l and 11,900 U/l; the CalB protein concentration was 1.18 g/l of culture supernatant. The characteristics of CalB recovered from the P. pastoris culture were compared with the commercial form of CalB produced in Aspergillus oryzae. The kinetic constants and specific activity, the effects of activity and stability on temperature and pH, the glycosylation extent, the degree of immobilization on macroporous resin and the yield of esterification reaction between oleic acid and n-butanol were almost identical to each other. Therefore, we successfully proved that the Pichia-based expression system for CalB in this study was industrially promising compared with one of the most efficient production systems. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  4. High-level extracellular protein production in Bacillus subtilis using an optimized dual-promoter expression system.

    Science.gov (United States)

    Zhang, Kang; Su, Lingqia; Duan, Xuguo; Liu, Lina; Wu, Jing

    2017-02-20

    We recently constructed a Bacillus subtilis strain (CCTCC M 2016536) from which we had deleted the srfC, spoIIAC, nprE, aprE and amyE genes. This strain is capable of robust recombinant protein production and amenable to high-cell-density fermentation. Because the promoter is among the factors that influence the production of target proteins, optimization of the initial promoter, P amyQ from Bacillus amyloliquefaciens, should improve protein expression using this strain. This study was undertaken to develop a new, high-level expression system in B. subtilis CCTCC M 2016536. Using the enzyme β-cyclodextrin glycosyltransferase (β-CGTase) as a reporter protein and B. subtilis CCTCC M 2016536 as the host, nine plasmids equipped with single promoters were screened using shake-flask cultivation. The plasmid containing the P amyQ' promoter produced the greatest extracellular β-CGTase activity; 24.1 U/mL. Subsequently, six plasmids equipped with dual promoters were constructed and evaluated using this same method. The plasmid containing the dual promoter P HpaII -P amyQ' produced the highest extracellular β-CGTase activity (30.5 U/mL) and was relatively glucose repressed. The dual promoter P HpaII -P amyQ' also mediated substantial extracellular pullulanase (90.7 U/mL) and α-CGTase expression (9.5 U/mL) during shake-flask cultivation, demonstrating the general applicability of this system. Finally, the production of β-CGTase using the dual-promoter P HpaII -P amyQ' system was investigated in a 3-L fermenter. Extracellular expression of β-CGTase reached 571.2 U/mL (2.5 mg/mL), demonstrating the potential of this system for use in industrial applications. The dual-promoter P HpaII -P amyQ' system was found to support superior expression of extracellular proteins in B. subtilis CCTCC M 2016536. This system appears generally applicable and is amenable to scale-up.

  5. Aspects of the Normalization of Managerial Accounting in Romania on a Microeconomic Level

    Directory of Open Access Journals (Sweden)

    Sorin BRICIU

    2011-03-01

    Full Text Available The article presents the general frame of the normalization of managerial accounting on a national level, following an incursion in its international normalization. The objectives of the normalization of managerial accounting in Romania are presented into detail, from the authors’ point of view, as well as the profile and attributions of the managerial accountant as a normalizer. The article ends with the authors’ conclusions related to the normalization of managerial accounting in Romania on a microeconomic level.

  6. Empathy, normality and responsiveness among street-level bureaucrats

    DEFF Research Database (Denmark)

    Møller, Marie Østergaard; Nielsen, Vibeke Lehmann

    2014-01-01

    Within the public sector it is a permanent dilemma that we on one hand – on the grounds of effectiveness and flexibility – want employees to have discretion and autonomy, but at the same time want to make sure that citizens and clients of the public sector are treated equally and independent of w...... this paper discusses and analyzes how perceptions of local target group’s problem portfolio (normality perceptions) conditions the behavioral effects of personal attributes/personality traits (differences in empathy)....

  7. Calcitonin serum levels in normal and in pathological conditions

    International Nuclear Information System (INIS)

    Ziliotto, D.; Luisetto, G.; Zanatta, G.P.; Cataldi, F.; Zangari, M.; Gangemi, M.; Melanotte, P.L.; Caira, S.

    1985-01-01

    Radioimmunoassay of calcitonin (CT) gives variable results because of differences in sensitivity and specificity of antibody preparations and because of the known immunoheterogeneity of circulating CT. The difficulties in interpretation of data has hindered our understanding of normal and abnormal CT physiology. The authors separated the biologically active CT monomer (CTm) from the higher molecular weight biologically inactive forms before RIA. It makes it possible to re-evaluate the behaviour of CT in physiological conditions and to study its changes in diseases in which bone and mineral metabolism are in some way compromised. (Auth.)

  8. Cell adhesion-mediated radioresistance (CAM-RR). Extracellular matrix-dependent improvement of cell survival in human tumor and normal cells in vitro

    International Nuclear Information System (INIS)

    Cordes, N.; Meineke, V.

    2003-01-01

    Background: Cell-extracellular matrix (ECM) contact is thought to have great impact on cellular mechanisms resulting in increased cell survival upon exposure to ionizing radiation. Several human tumor cell lines and normal human fibroblastic cell strains of different origin, all of them expressing the wide-spread and important integrin subunit β1, were irradiated, and clonogenic cell survival, β1-integrin cell surface expression, and adhesive functionality were investigated. Material and Methods: Human tumor cell lines A172 (glioblastoma), PATU8902 (pancreas carcinoma), SKMES1 (lung carcinoma), A549 (lung carcinoma), and IPC298 (melanoma) as well as normal human skin (HSF1) and lung fibroblasts (CCD32) and human keratinocytes (HaCaT) were irradiated with 0-8 Gy. Besides colony formation assays, β1-integrin cell surface expression by flow cytometry and adhesive functionality by adhesion assays were analyzed. Results: All cell lines showed improved clonogenic survival after irradiation in the presence of fibronectin as compared to plastic. Irradiated cells exhibited a significant, dose-dependent increase in β1-integrin cell surface expression following irradiation. As a parameter of the adhesive functionality of the β1-integrin, a radiation-dependent elevation of cell adhesion to fibronectin in comparison with adhesion to plastic was demonstrated. Conclusion: The in vitro cellular radiosensitivity is highly influenced by fibronectin according to the phenomenon of cell adhesion-mediated radioresistance. Additionally, our emerging data question the results of former and current in vitro cytotoxicity studies performed in the absence of an ECM. These findings might also be important for the understanding of malignant transformation, anchorage-independent cell growth, optimization of radiotherapeutic regimes and the prevention of normal tissue side effects on the basis of experimental radiobiological data. (orig.)

  9. Patients with fibromyalgia have normal serum levels of hyaluronic acid

    DEFF Research Database (Denmark)

    Bliddal, Henning; Møller, H J; Schaadt, M

    2000-01-01

    OBJECTIVE: To investigate the levels of hyaluronic acid (HA) in Danish patients with fibromyalgia (FM). METHODS: Serum levels of HA were determined in 53 patients with established FM and 55 control samples using a radiometric assay. Values were correlated to clinical disease severity variables...

  10. Comparative proteomic analysis of normal and collagen IX null mouse cartilage reveals altered extracellular matrix composition and novel components of the collagen IX interactome.

    Science.gov (United States)

    Brachvogel, Bent; Zaucke, Frank; Dave, Keyur; Norris, Emma L; Stermann, Jacek; Dayakli, Münire; Koch, Manuel; Gorman, Jeffrey J; Bateman, John F; Wilson, Richard

    2013-05-10

    Collagen IX is an integral cartilage extracellular matrix component important in skeletal development and joint function. Proteomic analysis and validation studies revealed novel alterations in collagen IX null cartilage. Matrilin-4, collagen XII, thrombospondin-4, fibronectin, βig-h3, and epiphycan are components of the in vivo collagen IX interactome. We applied a proteomics approach to advance our understanding of collagen IX ablation in cartilage. The cartilage extracellular matrix is essential for endochondral bone development and joint function. In addition to the major aggrecan/collagen II framework, the interacting complex of collagen IX, matrilin-3, and cartilage oligomeric matrix protein (COMP) is essential for cartilage matrix stability, as mutations in Col9a1, Col9a2, Col9a3, Comp, and Matn3 genes cause multiple epiphyseal dysplasia, in which patients develop early onset osteoarthritis. In mice, collagen IX ablation results in severely disturbed growth plate organization, hypocellular regions, and abnormal chondrocyte shape. This abnormal differentiation is likely to involve altered cell-matrix interactions but the mechanism is not known. To investigate the molecular basis of the collagen IX null phenotype we analyzed global differences in protein abundance between wild-type and knock-out femoral head cartilage by capillary HPLC tandem mass spectrometry. We identified 297 proteins in 3-day cartilage and 397 proteins in 21-day cartilage. Components that were differentially abundant between wild-type and collagen IX-deficient cartilage included 15 extracellular matrix proteins. Collagen IX ablation was associated with dramatically reduced COMP and matrilin-3, consistent with known interactions. Matrilin-1, matrilin-4, epiphycan, and thrombospondin-4 levels were reduced in collagen IX null cartilage, providing the first in vivo evidence for these proteins belonging to the collagen IX interactome. Thrombospondin-4 expression was reduced at the mRNA level

  11. Extracellular vesicles are present in mouse lymph and their level differs in atherosclerosis

    Directory of Open Access Journals (Sweden)

    Andreea Milasan

    2016-09-01

    Full Text Available The lymphatic system works in close collaboration with the cardiovascular system to preserve fluid balance throughout the body and is essential for the trafficking of antigen-presenting cells and lymphocytes to lymphoid organs. Recent findings have associated lymphatic dysfunction with the pathogenesis of cardiovascular-related diseases such as atherosclerosis, inflammation and obesity. Whether lymphatic dysfunction is a cause or a consequence of these diseases, as well as how, is under intensive investigation. Extracellular vesicles (EVs are submicron vesicles released by diverse cell types upon activation or apoptosis and are considered important biomarkers for several inflammatory diseases. Thus, it is critical to characterize the presence of EVs in various biological tissues and fluids to delineate their origins and, subsequently, their functions. In the past few years, new techniques allowing the quantitative and qualitative analysis of EVs have emerged, thus facilitating the onset of studies bridging these vesicles to the lymphatic system. Using several state-of-the-art approaches, this article reports the presence of diverse EVs inclusively derived from red blood cells and platelets in lymph of healthy animals. Our results suggest that lymph from atherosclerotic mice displays a higher concentration of EVs, bringing forward the concept that EVs contained in lymph could either be a biomarker for lymphatic dysfunction or, conversely, for inflammatory disease progression.

  12. Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease.

    Science.gov (United States)

    Liu, Bin; Li, Chenghai; Liu, Zijuan; Dai, Zonghan; Tao, Yunxia

    2012-09-11

    Polycystic Kidney Disease (PKD) kidneys exhibit increased extracellular matrix (ECM) collagen expression and metalloproteinases (MMPs) activity. We investigated the role of these increases on cystic disease progression in PKD kidneys. We examined the role of type I collagen (collagen I) and membrane bound type 1 MMP (MT1-MMP) on cyst development using both in vitro 3 dimensional (3D) collagen gel culture and in vivo PCK rat model of PKD. We found that collagen concentration is critical in controlling the morphogenesis of MDCK cells cultured in 3D gels. MDCK cells did not form 3D structures at collagen I concentrations lower than 1 mg/ml but began forming tubules when the concentration reaches 1 mg/ml. Significantly, these cells began to form cyst when collagen I concentration reached to 1.2 mg/ml, and the ratios of cyst to tubule structures increased as the collagen I concentration increased. These cells exclusively formed cyst structures at a collagen I concentration of 1.8 mg/ml or higher. Overexpression of MT1-MMP in MDCK cells significantly induced cyst growth in 3D collagen gel culture. Conversely, inhibition of MMPs activity with doxycycline, a FDA approved pan-MMPs inhibitor, dramatically slowed cyst growth. More importantly, the treatment of PCK rats with doxycycline significantly decreased renal tubule cell proliferation and markedly inhibited the cystic disease progression. Our data suggest that increased collagen expression and MMP activity in PKD kidneys may induce cyst formation and expansion. Our findings also suggest that MMPs may serve as a therapeutic target for the treatment of human PKD.

  13. Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Liu Bin

    2012-09-01

    Full Text Available Abstract Background Polycystic Kidney Disease (PKD kidneys exhibit increased extracellular matrix (ECM collagen expression and metalloproteinases (MMPs activity. We investigated the role of these increases on cystic disease progression in PKD kidneys. Methods We examined the role of type I collagen (collagen I and membrane bound type 1 MMP (MT1-MMP on cyst development using both in vitro 3 dimensional (3D collagen gel culture and in vivo PCK rat model of PKD. Results We found that collagen concentration is critical in controlling the morphogenesis of MDCK cells cultured in 3D gels. MDCK cells did not form 3D structures at collagen I concentrations lower than 1 mg/ml but began forming tubules when the concentration reaches 1 mg/ml. Significantly, these cells began to form cyst when collagen I concentration reached to 1.2 mg/ml, and the ratios of cyst to tubule structures increased as the collagen I concentration increased. These cells exclusively formed cyst structures at a collagen I concentration of 1.8 mg/ml or higher. Overexpression of MT1-MMP in MDCK cells significantly induced cyst growth in 3D collagen gel culture. Conversely, inhibition of MMPs activity with doxycycline, a FDA approved pan-MMPs inhibitor, dramatically slowed cyst growth. More importantly, the treatment of PCK rats with doxycycline significantly decreased renal tubule cell proliferation and markedly inhibited the cystic disease progression. Conclusions Our data suggest that increased collagen expression and MMP activity in PKD kidneys may induce cyst formation and expansion. Our findings also suggest that MMPs may serve as a therapeutic target for the treatment of human PKD.

  14. Extracellular DNA amplicon sequencing reveals high levels of benthic eukaryotic diversity in the central Red Sea

    KAUST Repository

    Pearman, John K.; Irigoien, Xabier; Carvalho, Susana

    2015-01-01

    The present study aims to characterize the benthic eukaryotic biodiversity patterns at a coarse taxonomic level in three areas of the central Red Sea (a lagoon, an offshore area in Thuwal and a shallow coastal area near Jeddah) based

  15. Effects of treadmill running on extracellular basal levels of glutamate and GABA at dentate gyrus of streptozotocin-induced diabetic rats

    Science.gov (United States)

    Reisi, Parham; Alaei, Hojjatallah; Babri, Shirin; Sharifi, Mohammad Reza; Mohaddes, Gisue; Soleimannejad, Elaheh; Rashidi, Bahman

    2010-01-01

    BACKGROUND: The present study evaluated the effects of treadmill running on extracellular basal levels of glutamate and GABA at dentate gyrus of streptozotocin-induced diabetic rats. METHODS: After 12 weeks of diabetes induction and exercise period, extracellular levels of glutamate and GABA were investigated. RESULTS: The results showed that glutamate levels were significantly decreased in diabetes-rest group comparing to the control-rest and the diabetes-exercise groups. CONCLUSIONS: The findings support the possibility that treadmill running is helpful in alleviating neurotransmitter homeostasis and alterations in transmission in diabetes mellitus. PMID:21526077

  16. Extracellular cyclophilin levels associate with parameters of asthma in phenotypic clusters.

    Science.gov (United States)

    Stemmy, Erik J; Benton, Angela S; Lerner, Jennifer; Alcala, Sarah; Constant, Stephanie L; Freishtat, Robert J

    2011-12-01

    Leukocyte persistence during chronic (quiescent) phases of asthma is a major hallmark of the disease. The mechanisms regulating these persistent leukocyte populations are not clearly understood. An alternative family of chemoattracting proteins, cyclophilins (Cyps), has recently been shown to contribute to leukocyte recruitment in animal models of allergic asthma. The goals of this study were to determine whether Cyps are present in asthma patients during the chronic phase of the disease and to investigate whether levels of Cyps associate with clinical parameters of disease severity. Nasal wash samples from an urban cohort of 137 patients of age 6-20 years with physician-diagnosed asthma were examined for the presence of cyclophilin A (CypA), cyclophilin B (CypB), as well as several other classical chemokines. Linear, logistic, or ordinal regressions were performed to identify associations between Cyps, chemokines, and clinical parameters of asthma. The asthma cohort was further divided into previously established phenotypic clusters (cluster 1: n = 55; cluster 2: n = 31; and cluster 3: n = 51) and examined for associations. Levels of CypB in the asthma group were highly elevated compared to nonasthmatic controls, while a slight increase in Monocyte Chemotactic Protein-1 (MCP-1) was also observed. CypA and MCP-1 were associated with levels of eosinophil cationic protein (ECP; a marker of eosinophil activation). Cluster-specific associations were found for CypA and CypB and clinical asthma parameters [e.g. forced expiratory volume in 1 second (FEV(1)) and ECP]. Cyps are present in nasal wash samples of asthma patients and may be a novel biomarker for clinical parameters of asthma severity.

  17. Extracellular matrix protein fibulin-1 plasma levels are associated with increased cardiovascular risk in chronic kidney disease

    DEFF Research Database (Denmark)

    Scholze, Alexandra

    INTRODUCTION AND AIMS: Fibulin-1 is one of the few extracellular matrix proteins present in blood in high concentrations. We aimed to define the relationship between plasma fibulin-1 levels and risk markers of cardiovascular disease in patients with chronic kidney disease. METHODS: Plasma fibulin-1...... hemodynamic and arterial stiffness indices. RESULTS: We observed a positive correlation of fibulin-1 levels with age (r=0.38; p=0.033), glycated hemoglobin (r=0.80; p=0.003), creatinine (r=0.35; p=0.045), and fibrinogen (r=0.39; p=0.027). Glomerular filtration rate and fibulin-1 were inversely correlated (r......=-0.57; p=0.022). There was a positive correlation between fibulin-1 and central pulse pressure (r=0.44; p=0.011) and central augmentation pressure (r=0.55; p=0.001). In a multivariable regression model, diabetes, creatinine, fibrinogen and central augmentation pressure were independent predictors...

  18. Increased Interleukin-32 Levels in Obesity Promote Adipose Tissue Inflammation and Extracellular Matrix Remodeling: Effect of Weight Loss.

    Science.gov (United States)

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Valentí, Víctor; Moncada, Rafael; Landecho, Manuel F; Silva, Camilo; Salvador, Javier; Frühbeck, Gema

    2016-12-01

    Interleukin (IL)-32 is a recently described cytokine involved in the regulation of inflammation. We aimed to explore whether IL-32 could function as an inflammatory and angiogenic factor in human obesity and obesity-associated type 2 diabetes. Samples obtained from 90 subjects were used in the study. Obese patients exhibited higher expression levels of IL-32 in visceral adipose tissue (AT) as well as in subcutaneous AT and peripheral blood mononuclear cells. IL32 was mainly expressed by stromovascular fraction cells, and its expression was significantly enhanced by inflammatory stimuli and hypoxia, whereas no changes were found after the incubation with anti-inflammatory cytokines. The addition of exogenous IL-32 induced the expression of inflammation and extracellular matrix-related genes in human adipocyte cultures, and IL32-silenced adipocytes showed a downregulation of inflammatory genes. Furthermore, adipocyte-conditioned media obtained from obese patients increased IL32 gene expression in human monocyte cultures, whereas the adipocyte-conditioned media from lean volunteers had no effect on IL32 mRNA levels. These findings provide evidence, for the first time, about the inflammatory and remodeling properties of IL-32 in AT, implicating this cytokine in obesity-associated comorbidities. © 2016 by the American Diabetes Association.

  19. Isolation of mouse mesenchymal stem cells with normal ploidy from bone marrows by reducing oxidative stress in combination with extracellular matrix

    Directory of Open Access Journals (Sweden)

    Wang Fang

    2011-07-01

    Full Text Available Abstract Background Isolation of mouse MSCs (mMSCs with normal ploidy from bone marrow remains challenging. mMSCs isolated under 20% O2 are frequently contaminated by overgrown hematopoietic cells, and could also be especially vulnerable to oxidative damage, resulting in chromosomal instability. Culture under low oxygen or extracellular matrix (ECM improves proliferation of MSCs in several species. We tested the hypothesis that culture under low oxygen in combination with ECM prepared from mouse embryonic fibroblast (MEF-ECM could be used to purify proliferative mMSCs, and to reduce oxidative damage and maintain their chromosomal stability. Results Optimization of culture conditions under 20% O2 resulted in immortalization of mMSCs, showing extensive chromosome abnormalities, consistent with previous studies. In contrast, culture under low oxygen (2% O2 improved proliferation of mMSCs and reduced oxidative damage, such that mMSCs were purified simply by plating at low density under 2% O2. MEF-ECM reduced oxidative damage and enhanced proliferation of mMSCs. However, these isolated mMSCs still exhibited high frequency of chromosome abnormalities, suggesting that low oxygen or in combination with MEF-ECM was insufficient to fully protect mMSCs from oxidative damage. Notably, antioxidants (alpha -phenyl-t-butyl nitrone (PBN and N-acetylcysteine (NAC further reduced DNA damage and chromosomal abnormalities, and increased proliferation of mMSCs. mMSCs isolated by the combination method were successfully used to generate induced pluripotent stem (iPS cells by ectopic expression of Oct4, Sox2, Klf4 and c-Myc. Conclusions We have developed a technique that allows to reduce the number of karyotypic abnormalities for isolation of primary mMSCs and for limited culture period by combination of low oxygen, MEF-ECM, antioxidants and low density plating strategy. The effectiveness of the new combination method is demonstrated by successful generation of i

  20. Temperature sensitivity of extracellular enzyme kinetics in subtropical wetland soils under different nutrient and water level conditions

    Science.gov (United States)

    Goswami, S.; Inglett, K.; Inglett, P.

    2012-12-01

    Microbial extracellular enzymes play an important role in the initial steps of soil organic matter decomposition and are involved in regulating nutrient cycle processes. Moreover, with the recent concern of climate change, microbial extracellular enzymes may affect the functioning (C losses, C sequestration, greenhouse gas emissions, vegetation changes) of different ecosystems. Hence, it is imperative to understand the biogeochemical processes that may be climate change sensitive. Here, we have measured the Michaelis Menten Kinetics [maximal rate of velocity (Vmax) and half-saturation constant (Km)] of 6 enzymes involved in soil organic matter decomposition (phosphatase, phosphodiesterase, β-D-glucosidase, cellobiohydrolase, leucine aminopeptidase, N-Acetyl-β-D glucosaminidase) in different nutrient(P) concentration both aerobically and anaerobically in Everglade water conservation area 2A (F1, F4-slough and U3-slough). Temperature sensitivity of different enzymes is assessed within soil of different P concentrations. We hypothesized that the temperature sensitivity of the enzyme changes with the biogeochemical conditions including water level and nutrient condition. Furthermore, we have tested specific hypothesis that higher P concentration will initiate more C demand for microbes leading to higher Vmax value for carbon processing enzymes in high P site. We found temperature sensitivity of all enzymes for Vmax and Km under both aerobic and anaerobic condition ranges from 0.6 to 3.2 for Vmax and 0.5 to 2.5 for Km. Q10 values of Km for glucosidase indicate more temperature sensitivity under anaerobic condition. Under aerobic condition higher temperature showed significant effect on Vmax for bisphosphatase between high P and low P site. Decreasing P concentration from F1 site to U3-S site had showed significant effect in all temperature on carbon processing enzyme. This suggests that in high P site, microbes will use more carbon-processing enzyme to get more carbon

  1. Radionuclide blood levels during cisternography of patients with normal-pressure hydrocephalus or Alzheimer's disease

    International Nuclear Information System (INIS)

    Mahaley, M.S. Jr.; Wilkinson, R.H. Jr.; Sivalingham, S.; Friedman, H.; Tyson, W.; Goodrich, J.K.

    1974-01-01

    Various diagnostic procedures were compared during investigations of 37 dementia patients undergoing differential study for normal-pressure hydrocephalus or Alzheimer's disease. A diminished radionuclide level in the blood, with abnormal cisternography and pneumoencephalography, provided the most valuable diagnostic evidence of normal-pressure hydrocephalus. (U.S.)

  2. Gold in semen: Level in seminal plasma and spermatozoa of normal ...

    African Journals Online (AJOL)

    The study was conducted to understand the amount of gold in semen of normal and different infertile conditions. Gold was estimated in normal (n38) and pathological conditions (n86) by employing Atomic Absorption Spectrophotometer. Gold level observed in seminal plasma was as follows: in normozoospermia (n38) ...

  3. Diurnal levels of immunoreactive erythropoietin in normal subjects and subjects with chronic lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Miller, M.E.; Garcia, J.F.; Cohen, R.A.; Cronkite, E.P.; Moccia, G.; Acevedo, J.

    1981-10-01

    Serum levels of immunoreactive erythropoietin (Ep) were measured in 48 normal male and female volunteers, ages 20-60 years, to establish a control value for Ep of 18.5 +/- 5.0 (mean +/- SD) mU/ml. Levels of the hormone were also measured sequentially over a 24 h period of time in an additional 17 normal volunteers with no diurnal variation. Diurnal levels of immunoreactive Ep were also measured in 30 subjects, with chronic lung disease. These patients, in contrast to normal subjects exhibited a diurnal variation in the level of immunoreactive Ep with peak levels occurring at midnight. The only variable measured which correlated with the serum immunoreactive Ep level in subjects with chronic lung disease was the level of carboxyhaemoglobin (P less than 0.02).

  4. A Study on Fasting Serum Gastrin level in Normal Subjects and Various Gastric Diseases by Radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yong Duck; Lee, Heon Sil; Park, Seung Uk; Park, Sung Hwi; Lee, Chong Suk; Lee, Hak Choong [National Medical Center, Seoul (Korea, Republic of)

    1981-09-15

    The fasting serum gastrin levels were measured by radioimmunoassay in 32 normal healthy subjects without recognized gastrointestinal symptoms and 93 patients with various gastric diseases, who were visited of admitted to National Medical Center from February to June, 1981. The following results were obtained; 1) The fasting mean serum gastrin level in normal subjects was 55.9+-26.3 pg/m1, and there was no difference between male and female. 2) The gastrin levels in gastric and duodenal ulcer were 85.0+-28.4 and 76.0+-43.0 pg/ml respectively, and it's values were elevated as compared with normal subjects. In gastric ulcer, the gastrin level was elevated than that of duodenal ulcer, but no significant difference in each other. 3) The gastrin level in stomach cancer was 89.5+-42.2 pg/ml, and it's values were markedly elevated as compared with values in normal subjects. 4) The gastrin level in gastritis was 73.4+-37. 4 pg/ml, and it's values were elevated as compared with values in normal subjects. 5) The gastrin level in post-gastrectomy state was 50.3+-16.3 pg/ml, and it's values were slightly decreased as compared with values in normal subjects.

  5. A Study on Fasting Serum Gastrin level in Normal Subjects and Various Gastric Diseases by Radioimmunoassay

    International Nuclear Information System (INIS)

    Lee, Yong Duck; Lee, Heon Sil; Park, Seung Uk; Park, Sung Hwi; Lee, Chong Suk; Lee, Hak Choong

    1981-01-01

    The fasting serum gastrin levels were measured by radioimmunoassay in 32 normal healthy subjects without recognized gastrointestinal symptoms and 93 patients with various gastric diseases, who were visited of admitted to National Medical Center from February to June, 1981. The following results were obtained; 1) The fasting mean serum gastrin level in normal subjects was 55.9±26.3 pg/m1, and there was no difference between male and female. 2) The gastrin levels in gastric and duodenal ulcer were 85.0±28.4 and 76.0±43.0 pg/ml respectively, and it's values were elevated as compared with normal subjects. In gastric ulcer, the gastrin level was elevated than that of duodenal ulcer, but no significant difference in each other. 3) The gastrin level in stomach cancer was 89.5±42.2 pg/ml, and it's values were markedly elevated as compared with values in normal subjects. 4) The gastrin level in gastritis was 73.4±37. 4 pg/ml, and it's values were elevated as compared with values in normal subjects. 5) The gastrin level in post-gastrectomy state was 50.3±16.3 pg/ml, and it's values were slightly decreased as compared with values in normal subjects.

  6. A Study on Fasting Serum Gastrin level in Normal Subjects and Various Gastric Diseases by Radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yong Duck; Lee, Heon Sil; Park, Seung Uk; Park, Sung Hwi; Lee, Chong Suk; Lee, Hak Choong [National Medical Center, Seoul (Korea, Republic of)

    1981-09-15

    The fasting serum gastrin levels were measured by radioimmunoassay in 32 normal healthy subjects without recognized gastrointestinal symptoms and 93 patients with various gastric diseases, who were visited of admitted to National Medical Center from February to June, 1981. The following results were obtained; 1) The fasting mean serum gastrin level in normal subjects was 55.9+-26.3 pg/m1, and there was no difference between male and female. 2) The gastrin levels in gastric and duodenal ulcer were 85.0+-28.4 and 76.0+-43.0 pg/ml respectively, and it's values were elevated as compared with normal subjects. In gastric ulcer, the gastrin level was elevated than that of duodenal ulcer, but no significant difference in each other. 3) The gastrin level in stomach cancer was 89.5+-42.2 pg/ml, and it's values were markedly elevated as compared with values in normal subjects. 4) The gastrin level in gastritis was 73.4+-37. 4 pg/ml, and it's values were elevated as compared with values in normal subjects. 5) The gastrin level in post-gastrectomy state was 50.3+-16.3 pg/ml, and it's values were slightly decreased as compared with values in normal subjects.

  7. Gold in semen: Level in seminal plasma and spermatozoa of normal ...

    African Journals Online (AJOL)

    K.P. Skandhan

    2016-07-01

    Jul 1, 2016 ... Gold level in sediment (spermatozoa) of normal was almost same as observed in its seminal plasma ... showed, gold was not detected in semen by Direct Couple ... Diffraction Analysis, revealed presence of gold throughout.

  8. Serum testosterone and gonadotropins levels in patients with premature ejaculation: A comparison with normal men

    Directory of Open Access Journals (Sweden)

    Mohammad G Mohseni

    2014-01-01

    Conclusion: Patients with PE have higher FT and FSH levels compared with normal men. The causative relationship between these entities and also the clinical importance of this finding has to be determined by more comprehensive studies.

  9. Impact of increasing alanine aminotransferase levels within normal range on incident diabetes

    OpenAIRE

    Chong-Shan Wang; Ting-Tsung Chang; Wei-Jen Yao; Shan-Tair Wang; Pesus Chou

    2012-01-01

    Abnormal alanine aminotransferase level (ALT) levels might be associated with type 2 diabetes, but whether higher ALT levels within the normal range predict the risk is unknown. Methods: We followed a community-based cohort of 3446 individuals who were ≥35 years old without diabetes and hepatitis B or C in southern Taiwan for 8 years (1997–2004) to study the risk for type 2 diabetes with different normal ALT levels. Results: Among the 337 incident diabetes cases, 16.0% were from those w...

  10. Association of Tumor Growth Factor-? and Interferon-? Serum Levels with Insulin Resistance in Normal Pregnancy

    OpenAIRE

    Jahromi, Abdolreza Sotoodeh; Sanie, Mohammad Sadegh; Yusefi, Alireza; Zabetian, Hassan; Zareian, Parvin; Hakimelahi, Hossein; Madani, Abdolhossien; Hojjat-Farsangi, Mohammad

    2015-01-01

    Pregnancy is related to change in glucose metabolism and insulin production. The aim of our study was to determine the association of serum IFN-? and TGF-? levels with insulin resistance during normal pregnancy. This cross sectional study was carried out on 97 healthy pregnant (in different trimesters) and 28 healthy non-pregnant women. Serum TGF-? and IFN-? level were measured by ELISA method. Pregnant women had high level TGF-? and low level IFN-? as compared non-pregnant women. Maternal se...

  11. Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice

    DEFF Research Database (Denmark)

    Barascuk, N; Vassiliadis, E; Zheng, Qiuju

    2011-01-01

    Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELISA...

  12. Higher TSH Levels Within the Normal Range Are Associated With Unexplained Infertility.

    Science.gov (United States)

    Orouji Jokar, Tahereh; Fourman, Lindsay T; Lee, Hang; Mentzinger, Katherine; Fazeli, Pouneh K

    2018-02-01

    Unexplained infertility (UI), defined as the inability to conceive after 12 months of unprotected intercourse with no diagnosed cause, affects 10% to 30% of infertile couples. An improved understanding of the mechanisms underlying UI could lead to less invasive and less costly treatment strategies. Abnormalities in thyroid function and hyperprolactinemia are well-known causes of infertility, but whether thyrotropin (TSH) and prolactin levels within the normal range are associated with UI is unknown. To compare TSH and prolactin levels in women with UI and women with a normal fertility evaluation except for an azoospermic or severely oligospermic male partner. Cross-sectional study including women evaluated at a large academic health system between 1 January 2000 and 31 December 2012 with normal TSH (levels within the normal range of the assay and ≤5 mIU/L) and normal prolactin levels (≤20 ng/mL) and either UI (n = 187) or no other cause of infertility other than an azoospermic or severely oligospermic partner (n = 52). TSH and prolactin. Women with UI had significantly higher TSH levels than controls [UI: TSH 1.95 mIU/L, interquartile range: (1.54, 2.61); severe male factor: TSH 1.66 mIU/L, interquartile range: (1.25, 2.17); P = 0.003]. This finding remained significant after we controlled for age, body mass index, and smoking status. Nearly twice as many women with UI (26.9%) had a TSH ≥2.5 mIU/L compared with controls (13.5%; P < 0.05). Prolactin levels did not differ between the groups. Women with UI have higher TSH levels compared with a control population. More studies are necessary to determine whether treatment of high-normal TSH levels decreases time to conception in couples with UI. Copyright © 2017 Endocrine Society

  13. Higher Levels of Albuminuria within the Normal Range Predict Incident Hypertension

    OpenAIRE

    Forman, John P.; Fisher, Naomi D.L.; Schopick, Emily L.; Curhan, Gary C.

    2008-01-01

    Higher levels of albumin excretion within the normal range are associated with cardiovascular disease in high-risk individuals. Whether incremental increases in urinary albumin excretion, even within the normal range, are associated with the development of hypertension in low-risk individuals is unknown. This study included 1065 postmenopausal women from the first Nurses’ Health Study and 1114 premenopausal women from the second Nurses’ Health Study who had an albumin/creatinine ratio

  14. Normal levels of plasma FSH and LH in the menstrual cycle as determined by radioimmunoassay

    International Nuclear Information System (INIS)

    Lemgruber, I.; Pinto, J.C.M.; Linhares, E.; Granafer, A.

    1981-01-01

    The biological methods were not able to establish adequately the separate determination of FSH and LH. The introduction of radioimmunoassay had allowed the identification of plasma FSH and LH for the purpose of routine clinical use. The utilization of commercial kits, however, obliges each laboratory to have normal levels of his own. Such is the finality of this work, studying samples from 200 normal women, hospitalized for surgical reasons and having not any endocrinological problem. (author) [pt

  15. Comparison of plasma endothelin levels between osteoporotic, osteopenic and normal subjects

    Directory of Open Access Journals (Sweden)

    Biçimoğlu Ali

    2005-09-01

    Full Text Available Abstract Background It has been demonstrated that endothelins (ET have significant roles in bone remodeling, metabolism and physiopathology of several bone diseases. We aimed to investigate if there was any difference between the plasma ET levels of osteoporotic patients and normals. Methods 86 patients (70 women and 16 men with a mean age of 62.6 (ranges: 51–90 years were included in this study. Patients were divided into groups of osteoporosis, osteopenia and normal regarding reported T scores of DEXA evaluation according to the suggestions of World Health Organization. According to these criteria 19, 43 and 24 were normal, osteopenic and osteoporotic respectively. Then total plasma level of ET was measured in all patients with monoclonal antibody based sandwich immunoassay (EIA method. One-way analysis of variance test was used to compare endothelin values between normals, osteopenics and osteoporotics. Results Endothelin total plasma level in patients was a mean of 98.36 ± 63.96, 100.92 ± 47.2 and 99.56 ± 56.6 pg/ml in osteoporotic, osteopenic and normal groups respectively. The difference between groups was not significant (p > 0.05. Conclusion No significant differences in plasma ET levels among three groups of study participants could be detected in this study.

  16. Comparison of 25-hydroxyvitamin D and Calcium Levels between Polycystic Ovarian Syndrome and Normal Women

    Directory of Open Access Journals (Sweden)

    Ashraf Moini

    2015-04-01

    Full Text Available Background: Given the relationship of vitamin D deficiency with insulin resistance syndrome as the component of polycystic ovary syndrome (PCOS, the main aim of this study was to compare serum level of 25- hydroxyvitamin D [25(OHD] between PCOS patients and normal individuals. Materials and Methods: A cross sectional study was conducted to compare 25(OHD level between117 normal and 125 untreated PCOS cases at our clinic in Arash Hospital, Tehran, Iran, during 2011-2012. The obtained levels of 25(OHD were classified as follows: lower than 25 nmol/ml as severe deficiency, between 25-49.9 nmol/ml as deficiency, 50-74.9 nmol/ml as insufficiency, and above 75 nmol/ml asnormal. In addition, endocrine and metabolic variables were evaluated. Results: Among PCOS patients, our findings shows 3(2.4% normal, 7(5.6% with insufficiency, 33(26.4% with deficiency and 82(65.6% with severe deficiency, whereas in normal participants, 5(4.3% normal, 4(3.4% with insufficiency, 28(23.9% with deficiency and 80(68.4% with severe deficiency. Comparison of 25(OHD level between two main groups showed no significant differences (p= 0.65. Also, the calcium and 25(OHD levels had no significant differences in patients with overweight (p=0.22 and insulin resistance (p=0.64. But we also found a relationship between 25(OHD level and metabolic syndrome (p=0.01. Furthermore, there was a correlation between 25(OHD and body mass index (BMI in control group (p=0.01, while the C-reactive protein (CRP level was predominantly higher in PCOS group (p<0.001. Conclusion: Although the difference of 25(OHD level between PCOS and healthy women is not significant, the high prevalence of 25(OHD deficiency is a real alarm for public health care system and may influence our results.

  17. Extracellular Matrix, Nuclear and Chromatin Structure and GeneExpression in Normal Tissues and Malignant Tumors: A Work inProgress

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, Virginia A.; Xu, Ren; Bissell, Mina J.

    2006-08-01

    Almost three decades ago, we presented a model where theextracellular matrix (ECM) was postulated to influence gene expressionand tissue-specificity through the action of ECM receptors and thecytoskeleton. This hypothesis implied that ECM molecules could signal tothe nucleus and that the unit of function in higher organisms was not thecell alone, but the cell plus its microenvironment. We now know that ECMinvokes changes in tissue and organ architecture and that tissue, cell,nuclear, and chromatin structure are changed profoundly as a result ofand during malignant progression. Whereas some evidence has beengenerated for a link between ECM-induced alterations in tissuearchitecture and changes in both nuclear and chromatin organization, themanner by which these changes actively induce or repress gene expressionin normal and malignant cells is a topic in need of further attention.Here, we will discuss some key findings that may provide insights intomechanisms through which ECM could influence gene transcription and howtumor cells acquire the ability to overcome these levels ofcontrol.

  18. Synuclein gamma predicts poor clinical outcome in colon cancer with normal levels of carcinoembryonic antigen

    Directory of Open Access Journals (Sweden)

    Xing Xiaofang

    2010-07-01

    Full Text Available Abstract Background Synuclein gamma (SNCG, initially identified as a breast cancer specific gene, is aberrantly expressed in many different malignant tumors but rarely expressed in matched nonneoplastic adjacent tissues. In this study, we investigated the prognostic potential of SNCG in colon cancer particularly in the patients with normal carcinoembryonic antigen (CEA levels. Methods SNCG levels were assessed immunohistochemically in cancer tissues from 229 colon adenocarcinoma patients with a mean follow-up of 44 months. Correlations between SNCG levels and clinicopathologic features, preoperative serum CEA level, and clinical outcome were analyzed statistically using SPSS. Results SNCG levels in colon adenocarcinoma were closely associated with intravascular embolus and tumor recurrence but independent of preoperative serum CEA levels. SNCG expression was an independent prognostic factor of a shorter disease-free survival (DFS and overall survival (OS (P P = 0.001, P = 0.001, 0.002 for 97 patients with normal preoperative serum CEA level. Conclusions Our results suggest for the first time that SNCG is a new independent predicator for poor prognosis in patients with colon adenocarcinoma, including those with normal CEA levels. Combination of CEA with SNCG improves prognostic evaluation for patients with colon adenocarcinoma.

  19. Comparison of Serum Homocystein and Folic Acid Levels in Gestational Diabetes with Normal Pregnancy

    Directory of Open Access Journals (Sweden)

    F. Movahed

    2015-07-01

    Full Text Available Introduction & Objective: High levels of homocystein are a risk factor for insulin resistance, diabetes mellitus and cardio-vascular complications. This study was done to assess serum homocystein and folic acid levels and their relationship in women with gestational diabetes and compare them with normal pregnant women. Materials & Methods: This analytic epidemiologic case-control study was performed in Qazvin Kosar hospital in 2013-2015. 120 singleton pregnant women with 24-28 weeks of gestation according to 2-hour 75g oral glucose tolerance test were assigned to two groups; gestational diabetes (n=60, and normal pregnancy (n=60. Serum homocystein and folic acid levels were measured in two groups. Data were analyzed with statistical t-test and correlation method. Results: In gestational diabetes serum homocystein level was significantly higher (P<0.001 and folic acid was significantly lower (P<0.001 than normal pregnancy group .No relation-ship was observed between serum homocystein and serum folate. In both groups, serum folic acid was significantly related to fasting blood sugar. This relationship was inverse in gesta-tional diabetes group (P<0.001, r = - 0.512 and direct in normal pregnancy group (P=0.001 r =0.417. Conclusion: It seems folic acid has a role in regulation of serum homocystein level and blood sugar.(Sci J Hamadan Univ Med Sci 2015; 22 (2: 93-98

  20. [Relationship between the Mandarin acceptable noise level and the personality traits in normal hearing adults].

    Science.gov (United States)

    Wu, Dan; Chen, Jian-yong; Wang, Shuo; Zhang, Man-hua; Chen, Jing; Li, Yu-ling; Zhang, Hua

    2013-03-01

    To evaluate the relationship between the Mandarin acceptable noise level (ANL) and the personality trait for normal-hearing adults. Eighty-five Mandarin speakers, aged from 21 to 27, participated in this study. ANL materials and the Eysenck Personality Questionnaire (EPQ) questionnaire were used to test the acceptable noise level and the personality trait for normal-hearing subjects. SPSS 17.0 was used to analyze the results. ANL were (7.8 ± 2.9) dB in normal hearing participants. The P and N scores in EPQ were significantly correlated with ANL (r = 0.284 and 0.318, P 0.05). Listeners with higher ANL were more likely to be eccentric, hostile, aggressive, and instabe, no ANL differences were found in listeners who were different in introvert-extravert or lying.

  1. Sleep-wake stability in narcolepsy patients with normal, low and unmeasurable hypocretin levels

    DEFF Research Database (Denmark)

    Hansen, Mathias Hvidtfelt; Kornum, Birgitte Rahbek; Jennum, Poul

    2017-01-01

    movement (REM) sleep, and the occurrence of sleep onset REM (SOREM) in the nocturnal polysomnography were also measured. RESULTS: Participants with undetectable hypocretin-1 levels had significantly higher frequencies of transitions than controls and those with normal hypocretin-1 levels. Participants...... hypocretin-1 levels in particular, but also low hypocretin-1 levels, were associated with a less stable phenotype featuring more sleep state transitions and SOREM episodes. In addition, there was a distinction between nocturnal and diurnal REM sleep in hypocretin-deficient participants, expressed...... as increased diurnal REM sleep, which was not reflected in nocturnal sleep....

  2. Rapid fluctuations in extracellular brain glucose levels induced by natural arousing stimuli and intravenous cocaine: fueling the brain during neural activation

    Science.gov (United States)

    Lenoir, Magalie

    2012-01-01

    Glucose, a primary energetic substrate for neural activity, is continuously influenced by two opposing forces that tend to either decrease its extracellular levels due to enhanced utilization in neural cells or increase its levels due to entry from peripheral circulation via enhanced cerebral blood flow. How this balance is maintained under physiological conditions and changed during neural activation remains unclear. To clarify this issue, enzyme-based glucose sensors coupled with high-speed amperometry were used in freely moving rats to evaluate fluctuations in extracellular glucose levels induced by brief audio stimulus, tail pinch (TP), social interaction with another rat (SI), and intravenous cocaine (1 mg/kg). Measurements were performed in nucleus accumbens (NAcc) and substantia nigra pars reticulata (SNr), which drastically differ in neuronal activity. In NAcc, where most cells are powerfully excited after salient stimulation, glucose levels rapidly (latency 2–6 s) increased (30–70 μM or 6–14% over baseline) by all stimuli; the increase differed in magnitude and duration for each stimulus. In SNr, where most cells are transiently inhibited by salient stimuli, TP, SI, and cocaine induced a biphasic glucose response, with the initial decrease (−20–40 μM or 5–10% below baseline) followed by a reboundlike increase. The critical role of neuronal activity in mediating the initial glucose response was confirmed by monitoring glucose currents after local microinjections of glutamate (GLU) or procaine (PRO). While intra-NAcc injection of GLU transiently increased glucose levels in this structure, intra-SNr PRO injection resulted in rapid, transient decreases in SNr glucose. Therefore, extracellular glucose levels in the brain change very rapidly after physiological and pharmacological stimulation, the response is structure specific, and the pattern of neuronal activity appears to be a critical factor determining direction and magnitude of physiological

  3. Data on copper level in the blood of patients with normal and abnormal angiography

    Directory of Open Access Journals (Sweden)

    Leila Amiri

    2016-12-01

    Full Text Available In this data article, we measured the levels of copper in the blood of patients undergoing coronary angiography. The samples were taken from patients with cardiovascular disease in Bushehr׳s university hospital, Iran. Patients were divided in two groups: normal angiography and abnormal angiography. After the chemical digestion of samples, the concentration levels of Cu in both groups were determined by using inductively coupled plasma optical spectrometry (ICP-OES.

  4. Sleep-wake stability in narcolepsy patients with normal, low and unmeasurable hypocretin levels.

    Science.gov (United States)

    Hansen, Mathias Hvidtfelt; Kornum, Birgitte Rahbek; Jennum, Poul

    2017-06-01

    To compare diurnal and nocturnal electrophysiological data from narcolepsy patients with undetectable (110 pg/mL) cerebrospinal fluid (CSF) hypocretin-1 levels. A total of 109 narcolepsy patients and 37 controls were studied; all had available CSF hypocretin-1 measurements. The sleep laboratory studies were conducted between 2008 and 2014. The study retrospectively examined measurements of sleep stage transitions in diurnal and nocturnal continuous polysomnography. The percentage distribution of time awake and rapid eye movement (REM) sleep, and the occurrence of sleep onset REM (SOREM) in the nocturnal polysomnography were also measured. Participants with undetectable hypocretin-1 levels had significantly higher frequencies of transitions than controls and those with normal hypocretin-1 levels. Participants with low hypocretin-1 levels showed more transitions than controls and, in some cases, also more than those with normal hypocretin-1. Participants with normal hypocretin-1 failed to show any significant difference from the controls, except in the overall diurnal transitions. Undetectable hypocretin-1 levels in particular, but also low hypocretin-1 levels, were associated with a less stable phenotype featuring more sleep state transitions and SOREM episodes. In addition, there was a distinction between nocturnal and diurnal REM sleep in hypocretin-deficient participants, expressed as increased diurnal REM sleep, which was not reflected in nocturnal sleep. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Decreased extracellular adenosine levels lead to loss of hypoxia-induced neuroprotection after repeated episodes of exposure to hypoxia.

    Directory of Open Access Journals (Sweden)

    Mei Cui

    Full Text Available Achieving a prolonged neuroprotective state following transient ischemic attacks (TIAs is likely to effectively reduce the brain damage and neurological dysfunction associated with recurrent stroke. HPC is a phenomenon in which advanced exposure to mild hypoxia reduces the stroke volume produced by a subsequent TIA. However, this neuroprotection is not long-lasting, with the effects reaching a peak after 3 days. Therefore, in this study, we investigated the use of multiple episodes of hypoxic exposure at different time intervals to induce longer-term protection in a mouse stroke model. C57BL/6 mice were subjected to different hypoxic preconditioning protocols: a single episode of HPC or five identical episodes at intervals of 3 days (E3d HPC or 6 days (E6d HPC. Three days after the last hypoxic exposure, temporary middle cerebral artery occlusion (MCAO was induced. The effects of these HPC protocols on hypoxia-inducible factor (HIF regulated gene mRNA expression were measured by quantitative PCR. Changes in extracellular adenosine concentrations, known to exert neuroprotective effects, were also measured using in vivo microdialysis and high pressure liquid chromatography (HPLC. Neuroprotection was provided by E6d HPC but not E3d HPC. HIF-regulated target gene expression increased significantly following all HPC protocols. However, E3d HPC significantly decreased extracellular adenosine and reduced cerebral blood flow in the ischemic region with upregulated expression of the adenosine transporter, equilibrative nucleoside transporter 1 (ENT1. An ENT1 inhibitor, propentofylline increased the cerebral blood flow and re-established neuroprotection in E3d HPC. Adenosine receptor specific antagonists showed that adenosine mainly through A1 receptor mediates HPC induced neuroprotection. Our data indicate that cooperation of HIF-regulated genes and extracellular adenosine is necessary for HPC-induced neuroprotection.

  6. Sex differences in plasma homovanillic acid levels in schizophrenia and normal controls: relation to neuroleptic resistance.

    Science.gov (United States)

    Sumiyoshi, T; Hasegawa, M; Jayathilake, K; Meltzer, H Y

    1997-03-01

    Plasma homovanillic acid (pHVA) levels were compared in a large number of neuroleptic-resistant and -responsive schizophrenic patients (male/female = 161/46) and normal controls (67/27), and correlated with various measures of psychopathology. Psychopathology was evaluated with the brief psychiatric rating scale, the Schedule for Affective Disorders and Schizophrenia-Change version (SADS-C) and SADS-C Global Assessment Scale, the Scale for Assessment of Negative Symptoms, the Scale for Assessment of Positive Symptoms (SAPS), and the Quality of Life Scale. No significant differences in pHVA levels between neuroleptic-resistant (n = 104) or -responsive (n = 103) schizophrenic patients, and normal controls, were found; however, there was a main effect for sex, due to higher pHVA levels in women than men. There were no diagnosis x gender or age effects on pHVA levels. No significant correlations were observed between psychopathology ratings and baseline pHVA levels, except with the Hallucinations subscale of SAPS in neuroleptic-responsive patients. Neither duration of neuroleptic washout nor plasma prolactin levels correlated with pHVA levels. Further studies on the origin and significance of the gender difference in pHVA are indicated.

  7. Epidemiological studies in the high and normal level radiation areas of Kerala

    International Nuclear Information System (INIS)

    Koya, P.K.M.

    2012-01-01

    High and normal level natural radiation areas of Kerala give unique opportunities to estimate the risk, if any, of chronic low dose exposure by direct epidemiological studies on human beings. Studies in the area are being carried out by Low Level Radiation Research Laboratory of Bhabha Atomic Research Centre in collaboration with Departments of Health and Family Welfare/Social Welfare of the Government of Kerala and local post graduate colleges. To assess the role of chronic low dose exposure in the induction/transmission of chromosomal alterations across generations, hospital based cytogenetic studies on newborns was carried out to estimate and compare the frequency of chromosomal aberrations and karyotypes anomalies in the high (areas with radiation dose of more than 1.50 mGy/year) and normal (areas with radiation dose of 1.50 mR/year or less) level radiation areas. A total of 1,267,788 metaphases from 27,295 (9,64,390 cells from 17,298 newborns of high and 3,03,398 cells from 9,997 newborns of normal level radiation areas) newborns was screened

  8. Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings

    International Nuclear Information System (INIS)

    Garcia, J.F.; Ebbe, S.N.; Hollander, L.; Cutting, H.O.; Miller, M.E.; Cronkite, E.P.

    1982-01-01

    Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 μl of sample, the assay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples show a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RA in the hematology clinic, which will most certainly be expanded with its more extensive use

  9. Study of AFP level in the blood serum of the 2223 normal pregnant women

    International Nuclear Information System (INIS)

    Wang Yunhui; Huo Tongshu; Ji Changqing; Mei Nan; Zhang Tao

    1993-01-01

    The authors have reported AFP level in the blood serum of 2223 normal pregnant women in different semesters by RIA method. All the data were made by statistical analysis. The result shows that the AFP level is normal during the first 12 weeks of pregnancy. Then, it gradually increases from the 13th week and reaches its maximum (184.6 +- 74.6 μg/l) at 32nd week. Later on it tends to decrease slowly, but still remains over 100 μg/l in parturition period. Therefore, it is suggested that AFP in pregnant women has substantial difference and regularity between different semesters but without any significant correlation with their ages

  10. Vitamin B12 and folate levels in normal population of northern Pakistan

    International Nuclear Information System (INIS)

    Madood-ul-mannan; Anwar, M.; Saleem, M.; Waqar, A.; Ahmad, M.

    1990-01-01

    Diagnosis of vitamin B12 or folate deficiency can not be made unless reference ranges of these vitamins in a given population are known. These serum levels depend upon the dietary intake of these vitamins which in turn depends upon the availability of foods containing these vitamins and the methods of cooking/processing. The latter vary in different populations. Therefore serum level of these vitamins would vary in different populations. Serum levels of vitamin B12 and folate were estimated by radioimmunoassay technique in 30 normal subjects of different age groups. The levels of vitamin B12 were found to be 215.2 pg/ml and that of folate 3.9 ng/ml. These values are much lower than those described for European population. It is therefore concluded that the cut off point of the levels of these vitamins should be different than the European figures. (author)

  11. Valgus-varus motion of the knee in normal level walking and stair climbing.

    Science.gov (United States)

    Yu, B; Stuart, M J; Kienbacher, T; Growney, E S; An, K-N

    1997-07-01

    OBJECTIVE: The knee valgus-varus moment and the knee angles were compared between normal level walking and stair climbing. DESIGN: Ten healthy subjects were tested for ascent, descent, and level walking. BACKGROUND: An understanding of the normal valgus-varus motion of the knee during stair climbing is needed to apply biomechanical analysis of stair climbing as a evaluation tool for knee osteoarthritis patients. METHODS: A motion analysis system, three force plates, and a flight of stairs were used to collect kinematic and kinetic data. The knee angles and moments were calculated from the collected kinematic and kinetic data. RESULTS: The knee varus angle for the maximum knee valgus moments in stair climbing was significantly greater than that in level walking. The knee valgus moment was significantly correlated to ground reaction forces and knee valgus-varus angle during stair climbing and level walking. CONCLUSIONS: There is a coupling between the knee valgus-varus motion and flexion-extension motion. Ground reaction forces are the major contributors to the within-subject variation in the knee valgus-varus moment during stair climbing and level walking. The knee valgus-varus angle is a major contributor to the between-subject variation in the knee valgus moment during stair climbing and level walking.

  12. Vasopressin and oxytocin levels during normal pregnancy: effects of chronic dietary sodium restriction.

    Science.gov (United States)

    van der Post, J A; van Buul, B J; Hart, A A; van Heerikhuize, J J; Pesman, G; Legros, J J; Steegers, E A; Swaab, D F; Boer, K

    1997-03-01

    Neurohypophysial hormones are thought to be involved in alterations in fluid balance during pregnancy and delivery. In the course of normal pregnancy intravascular volume is increased whereas sodium restriction is thought to reduce plasma volume and cardiac output. In the present study, we measured the effect of long-term severe sodium restriction on vasopressin (AVP) and oxytocin (OT) levels during normal pregnancy and after delivery. Fifty-nine healthy nulliparous women were randomized either for a low sodium diet (20 mmol sodium daily) or for a normal diet from week 12 of pregnancy onwards. Circulating plasma levels and urinary excretion of AVP and OT, their neurophysins (Np-AVP and Np-OT) and AVP bound to platelets were determined at regular intervals during pregnancy and after delivery. After completion of the study, women on a sodium-restricted diet were compared with control women on a normal diet using repeated measurement ANOVA with adjustment for potentially confounding variables. After randomization, a reduction in urinary sodium excretion of, on average, 40-82% was found. In general, no effect of sodium restriction could be demonstrated on the various parameters (0.53 sodium restriction compared with non-smokers having a normal diet (P = 0.018). For all parameters, clear changes were found in the course of pregnancy and puerperium (P pregnancy. After birth, free plasma AVP, platelet-bound AVP, OT, osmolality, sodium and potassium increased, while Np-AVP and Np-OT decreased. Although elevated Np-AVP and Np-OT levels during pregnancy seem to indicate increased release of neurohypophysial hormones, pregnancy up to 36 weeks of gestation is accompanied by low circulating AVP and OT levels. Long-term severe sodium restriction diminishes urinary AVP excretion in (non-smoking) pregnant women, without changing circulating levels of AVP and OT, despite the known reduction in circulating volume. The reduced circulating (platelet-bound) AVP levels during pregnancy

  13. Quantification of extracellular levels of corticosterone in the basolateral amygdaloid complex of freely-moving rats: a dialysis study of circadian variation and stress-induced modulation.

    Science.gov (United States)

    Bouchez, Gaëlle; Millan, Mark J; Rivet, Jean-Michel; Billiras, Rodolphe; Boulanger, Raphaël; Gobert, Alain

    2012-05-03

    Corticosterone influences emotion and cognition via actions in a diversity of corticolimbic structures, including the amygdala. Since extracellular levels of corticosterone in brain have rarely been studied, we characterized a specific and sensitive enzymatic immunoassay for microdialysis quantification of corticosterone in the basolateral amygdaloid complex of freely-moving rats. Corticosterone levels showed marked diurnal variation with an evening (dark phase) peak and stable, low levels during the day (light phase). The "anxiogenic agents", FG7142 (20 mg/kg) and yohimbine (10 mg/kg), and an environmental stressor, 15-min forced-swim, induced marked and sustained (1-3 h) increases in dialysis levels of corticosterone in basolateral amygdaloid complex. They likewise increased dialysis levels of dopamine and noradrenaline, but not serotonin and GABA. As compared to basal corticosterone levels of ~200-300 pg/ml, the elevation provoked by forced-swim was ca. 20-fold and this increase was abolished by adrenalectomy. Interestingly, stress-induced rises of corticosterone levels in basolateral amygdaloid complex were abrogated by combined but not separate administration of the corticotrophin releasing factor(1) (CRF(1)) receptor antagonist, CP154,526, and the vasopressin(1b) (V(1b)) receptor antagonist, SSR149,415. Underpinning their specificity, they did not block forced-swim-induced elevations in dopamine and noradrenaline. In conclusion, extracellular levels of corticosterone in the basolateral amygdaloid complex display marked diurnal variation. Further, they are markedly elevated by acute stressors, the effects of which are mediated (in contrast to concomitant elevations in levels of monoamines) by co-joint recruitment of CRF(1) and V(1b) receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Lower polyamine levels in breast milk of obese mothers compared to mothers with normal body weight.

    Science.gov (United States)

    Ali, M Atiya; Strandvik, B; Palme-Kilander, C; Yngve, A

    2013-07-01

    Obesity is associated with risks for mother and infant, and the mothers' dietary habits influence breast milk composition. Polyamines are secreted in breast milk and are essential for the regulation of intestinal and immune function in newborns and infants. The present study aimed to investigate the level of polyamines in human milk obtained from obese and normal weight mothers at different times of lactation. Breast milk from 50 mothers was obtained at day 3, and at 1 and 2 months after delivery. The mothers had normal body weight [body mass index (BMI) obese (BMI > 30 kg/m(2) ). A subgroup of obese mothers participated in a weight reduction programme during pregnancy. Polyamines were analysed using high-performance liquid chromatography. The total polyamine content was significantly lower at all times in breast milk from obese mothers compared to milk from controls. Spermine levels did not differ between groups at any time in contrast to the levels of putrescine and spermidine. Putrescine concentrations were highest on day 3 and spermidine and spermine were highest at 1 month of lactation. The obese mothers, who received dietary advice during pregnancy based on the Nordic Nutrition Recommendations, had higher concentrations of putrescine and spermidine in their milk than the obese mothers without any intervention. Polyamine concentrations were lower in breast milk from obese mothers compared to mothers with a normal weight. General dietary intervention in obese mothers increased the polyamine levels, suggesting that the low levels in obesity were at least partly associated with food habits. However, the consistency of spermine suggests a special metabolic function of this polyamine. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

  15. Liver histology in hepatitis C virus positive patients with normal and elevated alanine amino transferase levels

    International Nuclear Information System (INIS)

    Bhatty, S.A.; Shaikh, N.A.; Akhter, S.S.

    2009-01-01

    To compare liver histology in HCV RNA positive patients with normal and elevated Alanine Aminotransferase Level (AST). This Cohort (prospective) study was conducted at Civil Hospital Karachi from Jan 2007 to July 2007. Forty patients with positive HCV RNA were included. Their liver function tests were followed for three months. Those having normal ALT on three occasions were taken as controls and those having elevated ALT were taken as cases. Liver biopsy was performed, Specimens were reviewed by single pathologist. Scheuer's scoring for grading of inflammation and staging of fibrosis of chronic hepatitis was used. Out of Forty patients having positive HCV RNA, 14 (35%) were male and 26 (65%) were female. Mean ALT in control group was 27.3 +- 6.1mu/l, mean ALT in cases was 91.7 +- 39.95 mu/l. Mean age in controls was 34.2 +- 10.75 years and in cases was 33.6 +- 9.40 years. On histopathology, the mean grade of inflammation in controls was 1.40 +- 0.681 while in cases was 1.20 +- 0.834, which was not statistically significantly different in the two groups (p= 0.411). Similarly mean staging of fibrosis in controls was 1.20 +- 0.768 and in cases was 1.35 +- 1.348 which was also not statistically different in the two groups (p=0.668). Stage 3 and 4 fibrosis was seen only in raised ALT group and not in the controls. Patients with persistently normal ALT and elevated ALT, although had similar grading of inflammation but the fibrosis score was more in elevated ALT group. None of the patients with normal ALT had normal histology, so decision for antiviral treatment should be individualized in this group also (JPMA 59:832; 2009). (author)

  16. Normal levels of total body sodium and chlorine by neutron activation analysis

    International Nuclear Information System (INIS)

    Kennedy, N.S.J.; Eastell, R.; Smith, M.A.; Tothill, P.

    1983-01-01

    In vivo neutron activation analysis was used to measure total body sodium and chlorine in 18 male and 18 female normal adults. Corrections for body size were developed. Normalisation factors were derived which enable the prediction of the normal levels of sodium and chlorine in a subject. The coefficient of variation of normalised sodium was 5.9% in men and 6.9% in women, and of normalised chlorine 9.3% in men and 5.5% in women. In the range examined (40-70 years) no significant age dependence was observed for either element. Total body sodium was correlated with total body chlorine and total body calcium. Sodium excess, defined as the amount of body sodium in excess of that associated with chlorine, also correlated well with total body calcium. In females there was a mean annual loss of sodium excess of 1.2% after the menopause, similar to the loss of calcium. (author)

  17. Oral triiodothyronine normalizes triiodothyronine levels after surgery for pediatric congenital heart disease*.

    Science.gov (United States)

    Marwali, Eva M; Boom, Cindy E; Sakidjan, Indriwanto; Santoso, Anwar; Fakhri, Dicky; Kartini, Ay; Kekalih, Aria; Schwartz, Steven M; Haas, Nikolaus A

    2013-09-01

    This study was conducted to determine if oral triiodothyronine supplementation could prevent the decrease of serum triiodothyronine levels that commonly occurs after cardiopulmonary bypass for pediatric congenital heart surgery. Secondary objectives included identifying any significant adverse effects of oral triiodothyronine supplementation, including any effects on the thyroid/pituitary axis. Randomized, placebo-controlled, doubleblind clinical trial Operating room and ICU. Infants and children younger than 2 years of age undergoing congenital heart surgery using cardiopulmonary bypass (n = 43). Subjects were assigned to placebo (n = 15, group A) or one of two treatment groups: a low-dose group (group B, n = 14, 0.5 mcg/kg triiodothyronine orally every 24 hr for 3 d) or a high-dose group (group C, n = 14, 0.5 mcg/kg triiodothyronine orally every 12 hr for 3 d). Thyroid hormone, including total and free triiodothyronine levels at predetermined time points, potential side effects indicating hyperthyroidism, indicators of the thyroid-pituitary axis, and clinical endpoints. Oral triiodothyronine supplementation twice-daily maintained serum triiodothyronine levels within normal limits in group C, whereas serum levels progressively declined in groups A and B. A statistically significant difference in triiodothyronine levels between the treatment groups occurred between 18 and 36 hours post cross-clamp release, with the largest difference in serum levels between group C and group A noted at 36 hours post cross-clamp release (total triiodothyronine, 0.71 ± 0.15 [0.34-1.08] ng/mL [p triiodothyronine, 2.56 ± 0.49 [1.33-3.79] pg/mL [p triiodothyronine supplementation at a dose of 0.5 mcg/kg every 12 hours for 3 days can maintain total and free triiodothyronine levels within normal limits after open-heart surgery using cardiopulmonary bypass for congenital heart disease.

  18. HCV carriers with normal aminotransferase levels: “normal” does not always mean “healthy”

    Directory of Open Access Journals (Sweden)

    Claudio Puoti

    2013-04-01

    Full Text Available BACKGROUND Approximately 30% of patients with chronic HCV infection show persistently normal ALT levels (PNALT, and another 40% have minimally raised ALT values. Although formerly referred to as “healthy” or “asymptomatic” HCV carriers, it has now become clear that the majority of these patients have some degree of histological liver damage. Controversies still exist regarding the definition of “persistent” ALT normality, the virological and histological features of these subjects, and the natural history and optimal management of chronic hepatitis C (CHC with normal ALT. Most patients with normal ALT have histologically proven liver damage that may be significant (> F2 in up to 20% of patients, and might progress toward more severe degree of liver fibrosis. A significant proportion of patients (≥ 20% experiences periods of increased serum ALT (flare associated with disease progression. AIM OF THE STUDY The introduction of the new combination therapy of PEG-IFN plus ribavirin allowed response rates higher than 50%, with a favourable risk-benefit ratio also in patients with benign or slow progressive disease. Given the efficacy of the new treatments, which soon became the standard of care for CHC, it has been suggested that the issue of whether or not to treat subjects with PNALT should be re-evaluated. ALT levels may have less importance in deciding who should be treated. Many other factors might influence the decision to treat, such as the age of the patient, HCV genotype, liver histology, patient’s motivation, symptoms, extrahepatic manifestations, comorbid illness. The role of non-invasive tools for the assessment of liver fibrosis (transient hepatic elastography remains to be further validated.

  19. A radioimmunoassay for erythropoietin: serum levels in normal human subjects and patients with hemopoietic disorders

    International Nuclear Information System (INIS)

    Rege, A.B.; Brookins, J.; Fisher, J.W.

    1982-01-01

    An RIA for Ep has been developed that is highly sensitive and specific. A homogeneous Ep preparation was labeled with 125 I by the chloramine-T method to a specific activity of 90 to 136 micro Ci/microgram and immunoreactivity of 80%. Ep antiserum, which was produced to a human urinary Ep preparation (80 U/mg of protein), was adsorbed with normal human urinary and serum proteins without any loss in sensitivity of the RIA to increase the specificity of the assay. A good correlation was seen between the RIA and the exhypoxic polycythemic mouse assay (corr. coef. 0.967; slope 1.05 and y intercept 0.75). Ep titers in sera from 175 hematologically normal human subjects exhibited a normal frequency distribution and ranged between 5.8 and 36.6 mU/ml with a mean of 14.9 +/- 4.7 (S.D.) and median of 14.3 Serum Ep titers were markedly elevated in seven patients with aplastic anemia and one patient with pure red cell aplasia (1350 to 20,640 mU/ml) and were lower than normal in two patients with polycythemia vera (8.1 and 9.4 mU/ml). The serum Ep titers in a prenephrectomy patient with chronic glomerulonephritis (32.1 mU/ml) decreased to below normal levels (9.04 mU/ml) after nephrectomy. The cord serum erythropoietin titers in 10 IDM [90.82 +/- 134.1 (S.D.) mu/ml] returned to values within the normal range (13.86 +/- 5.55) on day 3 after birth, suggesting the utility of the RIA in elucidating the role of hypoxia and/or insulin in increased erythropoiesis in IDM. The serum Ep titers in patients with anemias and polycythemias were compared to those of normal human subjects and agreed well with pathophysiologic mechanisms of these hemopoietic disorders, confirming the validity of the RIA

  20. A radioimmunoassay for erythropoietin: serum levels in normal human subjects and patients with hemopoietic disorders

    International Nuclear Information System (INIS)

    Rege, A.B.; Brookins, J.; Fisher, J.W.

    1982-01-01

    An RIA for Ep has been developed that is highly sensitive and specific. A homogeneous Ep preparation was labeled with 125 I by the chloramine-T method to a specific activity of 90 to 136 μCi/μg and immunoreactivity of 80%. Ep antiserum, which was produced to a human urinary Ep preparation (80 U/mg of protein), was adsorbed with normal human urinary and serum proteins without any loss in sensitivity of the RIA to increase the specificity of the assay. A good correlation was seen between the RIA and the exhypoxic polycythemic mouse assay (corr. coef. 0.967; slope 1.05 and ''y'' intercept 0.75). Ep titers in sera from 175 hematologically normal human subjects exhibited a normal frequency distribution and ranged between 5.8 and 36.6 mU/ml with a mean of 14.9 +/- 4.7 (S.D.) and median of 14.3. Serum Ep titers were markedly elevated in seven patients with aplastic anemia and one patient with pure red cell aplasia (1350 to 20,640 mU/ml) and were lower than normal in two patients with polycythemia vera (8.1 and 9.4 mU/ml). The serum Ep titers in a prenephrectomy patient with chronic glomerulonephritis (31.1 mU/ml) decreased to below normal levels (9.04 mU/ml) after nephrectomy. The cord serum erythropoietin titers in 10 IDM [90.82 +/- 134.1 (S.D.) mu/ml] returned to values within the normal range (13.86 +/- 5.55) on day 3 after birth, suggesting the utility of the RIA in elucidating the role of hypoxia and/or insulin in increased erythropoiesis in IDM. The serum Ep titers in patients with anemias and polycythemias were compared to those of normal human subjects and agreed well with pathophysiologic mechanisms of these hemopoietic disorders, confirming the validity of the RIA

  1. Total levels of hippocampal histone acetylation predict normal variability in mouse behavior.

    Directory of Open Access Journals (Sweden)

    Addie May I Nesbitt

    Full Text Available Genetic, pharmacological, and environmental interventions that alter total levels of histone acetylation in specific brain regions can modulate behaviors and treatment responses. Efforts have been made to identify specific genes that are affected by alterations in total histone acetylation and to propose that such gene specific modulation could explain the effects of total histone acetylation levels on behavior - the implication being that under naturalistic conditions variability in histone acetylation occurs primarily around the promoters of specific genes.Here we challenge this hypothesis by demonstrating with a novel flow cytometry based technique that normal variability in open field exploration, a hippocampus-related behavior, was associated with total levels of histone acetylation in the hippocampus but not in other brain regions.Results suggest that modulation of total levels of histone acetylation may play a role in regulating biological processes. We speculate in the discussion that endogenous regulation of total levels of histone acetylation may be a mechanism through which organisms regulate cellular plasticity. Flow cytometry provides a useful approach to measure total levels of histone acetylation at the single cell level. Relating such information to behavioral measures and treatment responses could inform drug delivery strategies to target histone deacetylase inhibitors and other chromatin modulators to places where they may be of benefit while avoiding areas where correction is not needed and could be harmful.

  2. Renal failure in a patient with postpolio syndrome and a normal creatinine level.

    Science.gov (United States)

    Leming, Melissa K; Breyer, Michael J

    2012-01-01

    Patients with renal failure who are taking trimethoprim have an increased risk of developing hyperkalemia, which can cause muscle weakness. In patients with postpolio syndrome, a normal creatinine level could be abnormally high, renal failure is possible because of lack of creatinine production, and the muscle weakness from resultant hyperkalemia could be more severe because of their underlying condition. This abnormally high creatinine level has been termed from this point relative renal failure. The objective of the study was to review a case in which relative renal failure and hyperkalemia caused muscle weakness that manifested as shortness of breath and confusion with electrocardiographic changes. A dehydrated patient with relative renal failure and postpolio syndrome had taken trimethoprim-sulfamethoxazole that caused symptomatic hyperkalemia. The patient presented with muscle weakness, shortness of breath, and confusion, with her postpolio syndrome compounding the situation and likely making the muscle weakness more severe. A patient on trimethoprim with renal failure is at an increased risk of developing hyperkalemia. Patients with postpolio syndrome could have severe muscle weakness from the hyperkalemia and could have renal failure even with a normal creatinine level. This case report will remind treating physicians to evaluate such patients for hyperkalemia if they present with muscle weakness, especially if the patient has renal failure and is on trimethoprim. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Normal fasting plasma glucose levels and type 2 diabetes in young men.

    Science.gov (United States)

    Tirosh, Amir; Shai, Iris; Tekes-Manova, Dorit; Israeli, Eran; Pereg, David; Shochat, Tzippora; Kochba, Ilan; Rudich, Assaf

    2005-10-06

    The normal fasting plasma glucose level was recently defined as less than 100 mg per deciliter (5.55 mmol per liter). Whether higher fasting plasma glucose levels within this range independently predict type 2 diabetes in young adults is unclear. We obtained blood measurements, data from physical examinations, and medical and lifestyle information from men in the Israel Defense Forces who were 26 to 45 years of age. A total of 208 incident cases of type 2 diabetes occurred during 74,309 person-years of follow-up (from 1992 through 2004) among 13,163 subjects who had baseline fasting plasma glucose levels of less than 100 mg per deciliter. A multivariate model, adjusted for age, family history of diabetes, body-mass index, physical-activity level, smoking status, and serum triglyceride levels, revealed a progressively increased risk of type 2 diabetes in men with fasting plasma glucose levels of 87 mg per deciliter (4.83 mmol per liter) or more, as compared with those whose levels were in the bottom quintile (less than 81 mg per deciliter [4.5 mmol per liter], P for trend <0.001). In multivariate models, men with serum triglyceride levels of 150 mg per deciliter (1.69 mmol per liter) or more, combined with fasting plasma glucose levels of 91 to 99 mg per deciliter (5.05 to 5.50 mmol per liter), had a hazard ratio of 8.23 (95 percent confidence interval, 3.6 to 19.0) for diabetes, as compared with men with a combined triglyceride level of less than 150 mg per deciliter and fasting glucose levels of less than 86 mg per deciliter (4.77 mmol per liter). The joint effect of a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more and a fasting plasma glucose level of 91 to 99 mg per deciliter resulted in a hazard ratio of 8.29 (95 percent confidence interval, 3.8 to 17.8), as compared with a body-mass index of less than 25 and a fasting plasma glucose level of less than 86 mg per deciliter. Higher fasting plasma glucose

  4. Serum erythropoietin level in anemic and non-anemic nephrotic children with normal kidney functions

    International Nuclear Information System (INIS)

    Moustafa, A.M.E.; Moawad, A.T.; Gad, A.A.; Ahmed, S.M.

    2005-01-01

    Nephrotic syndrome (NS) is associated with a significant alteration in protein metabolism. While lowering the concentration of certain proteins, the disease often raises the level of certain other proteins. The current study aimed to investigate the serum erythropoietin (EPO) levels in children with NS either anemic or non-anemic and to compare them to children with iron deficiency anemia (IDA) and healthy controls with normal hemoglobin level (NHB). Sixteen nephrotic children with anemia (NS-A) and 15 nephrotic children with normal hemoglobin level (NS-NHB) were examined and compared with 10 children with iron deficiency anemia (IDA) and 10 healthy controls (NHB). Circulating serum EPO levels, blood indices and iron status were measured in nephrotic patients with anemia (NS-A) and compared to those nephrotic patients with normal HE (NS-NHB). Most NS-A children were steroid resistant. The NS-A children showed greater EPO levels than those without anemia (21.01 ±4.02 mlU/ml versus 9.18 ± 0.79 mlU/ml; P < 0.001) but their response to treatment of anemia was inappropriately low when compared to IDA (EPO 96.9 ±4.9 mlU/ml) despite similar HB concentration. A significant positive correlation was observed between serum EPO and serum albumin in NS-A (r = 0.84, P < 0.001) and in NS-NHB group (r = 0.89, P < 0.001). Moreover, a significant positive correlation was observed between serum EPO and HB in the nephrotic groups indicating a blunted EPO response to anemia in NS-A (r 0.63, P < 0.05) and in NS-NHB group (r = 0.80, P < 0.001). In conclusion, anemia is a common feature of NS and is present even before the worsening of kidney function. Depletion of the iron stores due to loss of iron and transferrin in urine due to massive proteinurea may contribute to the development of anemia, but it was found that iron replacement was ineffective alone

  5. Influence of insulin on beta-endorphin plasma levels in obese and normal weight subjects.

    Science.gov (United States)

    Brunani, A; Pincelli, A I; Pasqualinotto, L; Tibaldi, A; Baldi, G; Scacchi, M; Fatti, L M; Cavagnini, F

    1996-08-01

    To establish the possible role of hyperinsulinemia in the elevation of plasma beta-endorphin (beta-EP) levels observed in obese patients after an oral glucose load. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Two groups of six (age: 22-39 y, BMI: 30-48 kg/m2) and eight obese men (age: 18-37 y, BMI: 35-45 kg/m2), respectively, and five normal weight healthy men (age: 22-30 y, BMI 22-23 kg/m2). Glucose, insulin and beta-EP levels at baseline and every 30 min until 180 min during the OGTT; glucose, insulin, C-peptide and beta-EP concentrations at baseline and in steady state condition (i.e. during the last 30 min of insulin infusion) in the euglycemic-hyperinsulinemic clamp studies. In the six obese patients undergoing the OGTT a significant elevation of beta-EP plasma levels was observed between 60 and 90 min after glucose ingestion. In the clamp studies no significant differences in beta-EP plasma levels, blood glucose and serum insulin were observed between obese and normal weight subjects both at baseline and at steady state. A markedly diminished insulin sensitivity along with a lower inhibition of C-peptide during insulin infusion was observed in obese patients compared to control subjects. A rise in serum insulin levels unaccompanied by a concomitant increase in blood glucose concentration is unable to elicit a beta-EP response in obese patients.

  6. Higher levels of albuminuria within the normal range predict incident hypertension.

    Science.gov (United States)

    Forman, John P; Fisher, Naomi D L; Schopick, Emily L; Curhan, Gary C

    2008-10-01

    Higher levels of albumin excretion within the normal range are associated with cardiovascular disease in high-risk individuals. Whether incremental increases in urinary albumin excretion, even within the normal range, are associated with the development of hypertension in low-risk individuals is unknown. This study included 1065 postmenopausal women from the first Nurses' Health Study and 1114 premenopausal women from the second Nurses' Health Study who had an albumin/creatinine ratio who did not have diabetes or hypertension. Among the older women, 271 incident cases of hypertension occurred during 4 yr of follow-up, and among the younger women, 296 incident cases of hypertension occurred during 8 yr of follow-up. Cox proportional hazards regression was used to examine prospectively the association between the albumin/creatinine ratio and incident hypertension after adjustment for age, body mass index, estimated GFR, baseline BP, physical activity, smoking, and family history of hypertension. Participants who had an albumin/creatinine ratio in the highest quartile (4.34 to 24.17 mg/g for older women and 3.68 to 23.84 mg/g for younger women) were more likely to develop hypertension than those who had an albumin/creatinine ratio in the lowest quartile (hazard ratio 1.76 [95% confidence interval 1.21 to 2.56] and hazard ratio 1.35 [95% confidence interval 0.97 to 1.91] for older and younger women, respectively). Higher albumin/creatinine ratios, even within the normal range, are independently associated with increased risk for development of hypertension among women without diabetes. The definition of normal albumin excretion should be reevaluated.

  7. Sleep habits, food intake, and physical activity levels in normal and overweight and obese Malaysian children.

    Science.gov (United States)

    Firouzi, Somayyeh; Poh, Bee Koon; Ismail, Mohd Noor; Sadeghilar, Aidin

    2014-01-01

    This study aimed to determine the association between sleep habits (including bedtime, wake up time, sleep duration, and sleep disorder score) and physical characteristics, physical activity level, and food pattern in overweight and obese versus normal weight children. Case control study. 164 Malaysian boys and girls aged 6-€“12 years. Anthropometric measurements included weight, height, waist circumference, and body fat percentage. Subjects divided into normal weight (n = 82) and overweight/obese (n = 82) group based on World Health Organization 2007 BMI-for-age criteria and were matched one by one based on ethnicity, gender, and age plus minus one year. Questionnaires related to sleep habits, physical activity, and food frequency were proxy-reported by parents. Sleep disorder score was measured by Children Sleep Habit Questionnaire. Sleep disorder score and carbohydrate intake (%) to total energy intake were significantly higher in overweight/obese group (p < 0.01 and p < 0.05, respectively). After adjusting for age and gender, sleep disorder score was correlated with BMI (r = 0.275, p < 0.001), weight (r = 0.253, p < 0.001), and WC (r = 0.293, p < 0.001). Based on adjusted odd ratio, children with shortest sleep duration were found to have 4.5 times higher odds of being overweight/obese (odd ratio: 4.536, 95% CI: 1.912-€“8.898) compared to children with normal sleep duration. The odds of being overweight/obese in children with sleep disorder score higher than 48 were 2.17 times more than children with sleep disorder score less than 48. Children who sleep lees than normal amount, had poor sleep quality, and consumed more carbohydrates were at higher risk of overweight/obesity. © 2014 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.

  8. Equine alpha-fetoprotein levels in Lipizzaner mares with normal pregnancies and with pregnancy loss.

    Science.gov (United States)

    Vincze, Boglárka; Gáspárdy, András; Kulcsár, Margit; Baska, Ferenc; Bálint, Ádám; Hegedűs, György Tamás; Szenci, Ottó

    2015-12-01

    Alpha-fetoprotein has proved to be a good indicator of fetal well-being in human medicine for decades. Although this molecule is present in most of the mammalian species including horses, reference values in healthy and high-risk pregnant mares have not yet been published. The aim of the present study was to determine whether equine alpha-fetoprotein (eqAFP) is a good indicator of complicated pregnancies in Lipizzaner mares. A total of 111 serum samples from 30 mares have been analyzed for eqAFP levels throughout gestation (Days 60-325). After the pregnancy was confirmed, 23 mares had normal pregnancies with viable foals, six had late embryonic loss, and one of the mares aborted in the ninth gestational month. Equine alpha-fetoprotein concentrations significantly differed in the normal group (72.93 ± 49.25 pg/mL; mean ± standard deviation) and in the complicated pregnancy loss group (152 ± 36.48 pg/mL; mean ± standard deviation). The mares' age, gestational age, and the conception rate significantly affected the alpha-fetoprotein concentrations in the normal group. Furthermore, notable individual differences occurred in eqAFP concentrations between mares. Equine alpha-fetoprotein seems to be an important indicator of fetal well-being in horses, but there are still some unanswered questions (levels in foals of different age, ponies, and draft horses) regarding this serum protein. Large-scale studies are needed to assess the specificity, sensitivity, and reliability of this test as a possible future diagnostic tool for fetal well-being in horses. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Effect of AGE and Sex on thyroid hormone levels in normal egyptian individuals using RIA technique

    International Nuclear Information System (INIS)

    Abdel-Aziz, S.M.; El-Seify, S.; Megahed, Y.M.; El-Arab, A.

    1993-01-01

    This work aims to estimate total serum levels of thyroid hormones, namely triiodothyronine (T 3 ) and thyroxine (T 4 ) as well as the pituitary thyrotropin (TSH) in different categories of normal egyptian individuals classified according to age and sex. Radioimmunoassay (RIA) and immunoradiometritassay (IRMA) techniques were used. Results of this study indicate that T 3 and T 4 concentrations decreased significantly with advancing age. This decrement was statistically significant in both sexes and could be attributed to the decline in TBG concentration in the elderly. TSH level was not influenced by sex, however, a slight decrease was observed in the elderly perhaps due to decreased TSH receptors and or cyclic AMP activity. 3 figs., 2 tabs

  10. Reduced interhemispheric interaction in non-autistic individuals with normal but high levels of autism traits.

    Science.gov (United States)

    O'Keefe, Natalie; Lindell, Annukka K

    2013-11-01

    People with autism spectrum disorder (ASD) show superior performance for tasks requiring detail-focused processing. Atypical neural connectivity and reduced interhemispheric communication are posited to underlie this cognitive advantage. Given recent conceptualization of autism as a continuum, we sought to investigate whether people with normal but high levels of autism like traits (AQ) also exhibit reduced hemispheric interaction. Sixty right-handed participants completed the AQ questionnaire (Baron-Cohen, Wheelwright, Skinner, Martin, & Clubley, 2001) and a lateralised letter matching task that assessed unilateral and bilateral performance in response to simple (physical) and complex (identity) matches. Whereas people with low self-rated AQ scores showed a bilateral advantage for the more complex task, indicating normal interhemispheric interaction, people in the high AQ group failed to show a bilateral gain for the computationally demanding stimuli. This finding of disrupted interhemispheric interaction converges with a dimensional conceptualisation of ASD, suggesting that the structural anomalies of ASD extend to non-autistic individuals with high levels of autism traits. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Overweight and obese children have lower cortisol levels than normal weight children.

    Science.gov (United States)

    Kjölhede, E Allansson; Gustafsson, P E; Gustafsson, P A; Nelson, N

    2014-03-01

    The stress hormone cortisol is vital to survival, and a disturbed circadian rhythm can be deleterious to health. However, little is known about cortisol levels in healthy children. The aim of this study was to examine cortisol levels in relation to body mass index (BMI), age and sex. Salivary samples were collected in early morning, late morning and evening, on four consecutive days, from 342 children aged 6-12 years using Salivette(®) tubes. Samples were analysed using a commercial enzyme immunoassay (EIA). School nurses measured the children's height and weight, and these measurements were used to calculate their BMI. The children displayed a circadian rhythm in cortisol secretion, with morning zeniths and evening nadirs. Average cortisol levels in early morning, late morning and evening were significantly lower in overweight and obese children than in their normal weight counterparts. Cortisol levels did not vary significantly with age or sex. Our findings may suggest cortisol suppression in overweight and obese children. We found no evidence that sex or age influences cortisol levels. These findings highlight the need for further research on the relationship between stress and obesity in children. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  12. Normal blood magnesium levels in volunteers of Rawalpindi by atomic absorption absorption technique

    International Nuclear Information System (INIS)

    Ahmed, I.; Rehman, S.; Yawar, W.; Rusheed, A.; Ahraf, M.; Syed, N.H.

    1999-01-01

    Magnesium levels in whole blood samples of 67 healthy volunteers (mean 6.46 -+ 0.221; range 1.345 - 13.163 mg/dL) of Rawalpindi district have been determined by flame atomic absorption spectrophotometric method. Magnesium levels of 41 male and 26 female subjects including doctors, nurses, patients attendees, medical students, sweepers and peons of Rawalpindi Medical College and Rawalpindi General Hospital revealed the normal mean blood levels of 6.088 - + 0.258 mg/dL (range 1.345 - 10.679 mg/dL)and 7.060 -+ 0.375 mg/dL (range 4.495 - 13.163 mg/dL),P<0.05 respectively. Only 10 male volunteers were smokers exhibiting 6.768 -+ 0.558 mg/dL (range 4.466 -10.679 mg/dL). Significant relationship was found in magnesium levels between males and females of poor socio-economic group (P<0.05). No relationship occurred between male smokers and non-smokers and magnesium levels in the age groups of males or females or both, when data was compared by 't' test. (author)

  13. Effects of delivery on maternal & neonatal irisin levels in normal and preeclamptic pregnant women.

    Science.gov (United States)

    Foda, Ashraf A; Foda, Engy A

    2017-10-01

    The aim of this work was to measure the irisin levels in maternal and umbilical cord serums at cesarean section and vaginal delivery. This is a case-control study conducted at the Obstetric Department of the Mansoura University Hospital, Mansoura University, Egypt. The 150 nulliparous cases were divided into three groups. Serum irisin concentrations were assayed by enzyme-linked immunosorbent assay (ELISA) method. Unpaired t-test and correlation were done by using the Statistical Package for Social Scientists (SPSS). The maternal irisin levels in cases with mild preeclampsia were found to be significantly lower than that of the normal cases. In cases with mild preeclampsia, the maternal irisin levels early in labor for vaginal deliveries were significantly higher than that during cesarean section. The maternal irisin levels after vaginal deliveries were significantly higher than the levels early in labor. The maternal serum irisin was a significantly correlated with the duration of the first stage. The umbilical cord serum irisin levels were significantly correlated with the neonatal weight and with the duration of the first stage of labor. Labor is a strong stimulus to the release of irisin into the maternal and fetal circulations. Neonatal serum irisin levels are positively correlated with the birth weight and with the duration of the first stage. The neonatal birth weight and the duration of the first stage of labor are positively correlated with the umbilical cord serum irisin levels. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  14. Assessment of serum HE4 levels throughout the normal menstrual cycle.

    Science.gov (United States)

    Moore, Richard G; Plante, Beth; Hartnett, Erin; Mitchel, Jessica; Raker, Christine A; Vitek, Wendy; Eklund, Elizabeth; Lambert-Messerlian, Geralyn

    2017-07-01

    Human epididymis protein 4 is a serum biomarker to aid in differentiating benign and malignant disease in women with a pelvic mass. Interpretation of human epididymis protein 4 results relies on robust normative data. The purpose of this study was to evaluate whether human epididymis protein 4 levels are variable in women during the normal menstrual cycle. Healthy women, 18-45 years old, with regular menstrual cycles were recruited from community gynecologic practices in Rhode Island. Women consented to enroll and to participate by the donation of blood and urine samples at 5 specific times over the course of each cycle. Levels of reproductive hormones and human epididymis protein 4 were determined. Data were analyzed with the use of linear regression after log transformation. Among 74 enrolled cycles, 53 women had confirmed ovulation during the menstrual cycle and completed all 5 sample collections. Levels of estradiol, progesterone, and luteinizing hormone displayed the expected menstrual cycle patterns. Levels of human epididymis protein 4 in serum were relatively stable across the menstrual cycle, except for a small ovulatory (median, 37.0 pM) increase. Levels of human epididymis protein 4 in urine, after correction for creatinine, displayed the same pattern of secretion observed in serum. Serum human epididymis protein 4 levels are relatively stable across the menstrual cycle of reproductive-aged women and can be determined on any day to evaluate risk of ovarian malignancy. A slight increase is expected at ovulation; but even with this higher human epididymis protein 4 level, results are well within the healthy reference range for women (<120 pM). Levels of human epididymis protein 4 in urine warrant further investigation for use in clinical practice as a simple and convenient sample. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. High normal fasting glucose level in obese youth: a marker for insulin resistance and beta cell dysregulation.

    LENUS (Irish Health Repository)

    O'Malley, G

    2010-06-01

    A high but normal fasting plasma glucose level in adults is a risk factor for future development of type 2 diabetes mellitus and cardiovascular disease. We investigated whether normal fasting plasma glucose levels (<5.60 mmol\\/l) are associated with decreases in insulin sensitivity and beta cell function, as well as an adverse cardiovascular profile in obese youth.

  16. Comparison of self-esteem level of adolescents with cochlear implant and normal hearing.

    Science.gov (United States)

    Sahli, Sanem; Belgin, Erol

    2006-09-01

    The purpose of this study is to compare the levels of self-esteem of adolescents with cochlear implants (before and after cochlear implantation) and the ones who have normal hearing. For this purpose, Rosenberg self-esteem scale is applied upon the study group which consists of 30 adolescents with cochlear implant between the ages of 12-19 and upon the control group which consists of 60 adolescents having the similar characteristics. The scale is used to evaluate the level of self-esteem of adolescents with cochlear implant and with normal hearing. At the end of the application, the scores of these two groups which they got according to their answers were compared statistically. When the results were examined, there seemed to be no significant difference statistically between the self-esteem values of the cochlear implant group and the control group. Apart from this, there seemed to be significant difference statistically between the self-esteem values of the before cochlear implantation and control group. In this study, we examined changes in the level of self-esteem according to different variables. As a result, it was found out that in both groups levels of self-esteem was higher for adolescents who had had preschool education, had brothers/sisters, high level of income, whose mother was working and whose father and mother had higher levels of education. On the other hand, the birth sequence and the child's father's profession did not seem to have any effect on the child's level of self-esteem. As a result of these findings, it was thought that cochlear implantation had a positive effect on life quality and it was suggested that the adolescents and their families should get assistance from experts about the characteristics and principles of approaching the child in this period. The adolescent should be directed towards social activities and courses, their positive sides should be supported and further studies should be carried out with different case groups on

  17. Normal dietary levels of radium-226, radium-228, lead-210, and polonium-210 for man

    International Nuclear Information System (INIS)

    Holtzman, R.B.

    1980-01-01

    A review of the literature and the results of some recent measurements on the levels in man's diet of the naturally occurring radionuclides 226 Ra, 228 Ra, 210 Pb, and 210 Po are presented. Intakes in other countries are similar to those in the United States, but in localized populations the 226 Ra intake can be 8 or more pCi/day. The few data on 228 Ra show that intake of this nuclide is about 80% that of 226 Ra except in monazite areas where intakes of up to 160 pCi 228 Ra/day are reported. Drinking water contributes less than 5% to daily intake except in special areas. For 210 Pb, higher levels have been noted for Germany and the Union of Soviet Socialist Republics than for the United States. Persons in the Arctic who consume reindeer or caribou meat may ingest 210 Pb at the rate of 10 to 40 pCi/day. Normal dietary levels of 210 Po are about 20 to 30% higher than those of 210 Pb, except in the Arctic. The levels of these nuclides in classes of foods are compared to show that the higher levels observed in certain diets are due to the levels in particular foods. Because of the high levels of 210 Pb intake in Japan, total skeletal dose rates in that country are estimated to be more than twice those in the United States. The use of dietary intake for estimating metabolic parameters, such as intestinal absorption of 226 Ra and 210 Pb, is discussed

  18. Low-level ultrahigh-frequency and ultrashort-pulse blue laser irradiation enhances osteoblast extracellular calcification by upregulating proliferation and differentiation via transient receptor potential vanilloid 1.

    Science.gov (United States)

    Mikami, Risako; Mizutani, Koji; Aoki, Akira; Tamura, Yukihiko; Aoki, Kazuhiro; Izumi, Yuichi

    2018-04-01

    Low-level laser irradiation (LLLI) exerts various biostimulative effects, including promotion of wound healing and bone formation; however, few studies have examined biostimulation using blue lasers. The purpose of this study was to investigate the effects of low-level ultrahigh-frequency (UHF) and ultrashort-pulse (USP) blue laser irradiation on osteoblasts. The MC3T3-E1 osteoblast cell line was used in this study. Following LLLI with a 405 nm newly developed UHF-USP blue laser (80 MHz, 100 fs), osteoblast proliferation, and alkaline phosphatase (ALP) activity were assessed. In addition, mRNA levels of the osteoblast differentiation markers, runt-related transcription factor 2 (Runx2), osterix (Osx), alkaline phosphatase (Alp), and osteopontin (Opn) was evaluated, and extracellular calcification was quantified. To clarify the involvement of transient receptor potential (TRP) channels in LLLI-induced biostimulation, cells were treated prior to LLLI with capsazepine (CPZ), a selective inhibitor of TRP vanilloid 1 (TRPV1), and subsequent proliferation and ALP activity were measured. LLLI with the 405 nm UHF-USP blue laser significantly enhanced cell proliferation and ALP activity, compared with the non-irradiated control and LLLI using continuous-wave mode, without significant temperature elevation. LLLI promoted osteoblast proliferation in a dose-dependent manner up to 9.4 J/cm 2 and significantly accelerated cell proliferation in in vitro wound healing assay. ALP activity was significantly enhanced at doses up to 5.6 J/cm 2 , and expression of Osx and Alp mRNAs was significantly increased compared to that of the control on days 3 and 7 following LLLI at 5.6 J/cm 2 . The extent of extracellular calcification was also significantly higher as a result of LLLI 3 weeks after the treatment. Measurement of TRPV1 protein expression on 0, 3, and 7 days post-irradiation revealed no differences between the LLLI and control groups; however, promotion of cell

  19. Increased Obesity-Associated Circulating Levels of the Extracellular Matrix Proteins Osteopontin, Chitinase-3 Like-1 and Tenascin C Are Associated with Colon Cancer.

    Directory of Open Access Journals (Sweden)

    Victoria Catalán

    Full Text Available Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC, promoting a microenvironment favorable for tumor growth.Serum samples obtained from 79 subjects [26 lean (LN and 53 obese (OB] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (44 without CC and 35 with CC. Anthropometric measurements as well as circulating metabolites and hormones were determined. Circulating concentrations of the ECM proteins osteopontin (OPN, chitinase-3-like protein 1 (YKL-40, tenascin C (TNC and lipocalin-2 (LCN-2 were determined by ELISA.Significant differences in circulating OPN, YKL-40 and TNC concentrations between the experimental groups were observed, being significantly increased due to obesity (P<0.01 and colon cancer (P<0.05. LCN-2 levels were affected by obesity (P<0.05, but no differences were detected regarding the presence or not of CC. A positive association (P<0.05 with different inflammatory markers was also detected.To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics.

  20. Plasma levels of norepinephrine during the periovulatory period in normal women

    International Nuclear Information System (INIS)

    Badano, A.R.; Nagle, C.A.; Casas, P.R.F.; Miechi, H.; Mirkin, A.; Turner, D.E.; Aparicio, N.; Rosner, J.M.

    1978-01-01

    Eleven normally cycling women in whom laparotomy was indicated for benign gynecologic pathology were studied. Surgery was performed on day 0 (expected day of ovulation). Blood samples were drawn daily from day -8 to day -4, and every 8 hours from day -3 to day +2; estradiol (E 2 ), progesterone (P), norepinephrine (NE), and LH were determined by RIA. Ovulation was certified by ovarian visualization and biopsy during laparotomy. In nine ovulatory patients mean E 2 peak was found 48 hours before LH peak. Mean NE levels showed minimal variations until 48 hours before LH peak; 8 hours after E 2 peak mean NE values increased significantly, fell 8 hours later, and rose immediately again, reaching maximal levels 24 hours after E 2 peak. These values remained high until 16 hours before the LH peak and decreased gradully, thereafter reaching basal levels 32 hours after LH peak. Two anovulatory patients showed an atypical pattern of ovarian steroids and LH secretion and NE showed large variations without any correlation with estradiol or LH levels. This study confirms previous findings in women and experimental work in animals regarding the existence of a noradrenergic trigger mechanism to the LH ovulatory discharge

  1. EGSIEM combination service: combination of GRACE monthly K-band solutions on normal equation level

    Science.gov (United States)

    Meyer, Ulrich; Jean, Yoomin; Arnold, Daniel; Jäggi, Adrian

    2017-04-01

    The European Gravity Service for Improved Emergency Management (EGSIEM) project offers a scientific combination service, combining for the first time monthly GRACE gravity fields of different analysis centers (ACs) on normal equation (NEQ) level and thus taking all correlations between the gravity field coefficients and pre-eliminated orbit and instrument parameters correctly into account. Optimal weights for the individual NEQs are commonly derived by variance component estimation (VCE), as is the case for the products of the International VLBI Service (IVS) or the DTRF2008 reference frame realisation that are also derived by combination on NEQ-level. But variance factors are based on post-fit residuals and strongly depend on observation sampling and noise modeling, which both are very diverse in case of the individual EGSIEM ACs. These variance factors do not necessarily represent the true error levels of the estimated gravity field parameters that are still governed by analysis noise. We present a combination approach where weights are derived on solution level, thereby taking the analysis noise into account.

  2. Impact of Millimeter-Level Margins on Peripheral Normal Brain Sparing for Gamma Knife Radiosurgery

    International Nuclear Information System (INIS)

    Ma, Lijun; Sahgal, Arjun; Larson, David A.; Pinnaduwage, Dilini; Fogh, Shannon; Barani, Igor; Nakamura, Jean; McDermott, Michael; Sneed, Penny

    2014-01-01

    Purpose: To investigate how millimeter-level margins beyond the gross tumor volume (GTV) impact peripheral normal brain tissue sparing for Gamma Knife radiosurgery. Methods and Materials: A mathematical formula was derived to predict the peripheral isodose volume, such as the 12-Gy isodose volume, with increasing margins by millimeters. The empirical parameters of the formula were derived from a cohort of brain tumor and surgical tumor resection cavity cases (n=15) treated with the Gamma Knife Perfexion. This was done by first adding margins from 0.5 to 3.0 mm to each individual target and then creating for each expanded target a series of treatment plans of nearly identical quality as the original plan. Finally, the formula was integrated with a published logistic regression model to estimate the treatment-induced complication rate for stereotactic radiosurgery when millimeter-level margins are added. Results: Confirmatory correlation between the nominal target radius (ie, R T ) and commonly used maximum target size was found for the studied cases, except for a few outliers. The peripheral isodose volume such as the 12-Gy volume was found to increase exponentially with increasing Δ/R T , where Δ is the margin size. Such a curve fitted the data (logarithmic regression, R 2 >0.99), and the 12-Gy isodose volume was shown to increase steeply with a 0.5- to 3.0-mm margin applied to a target. For example, a 2-mm margin on average resulted in an increase of 55% ± 16% in the 12-Gy volume; this corresponded to an increase in the symptomatic necrosis rate of 6% to 25%, depending on the Δ/R T values for the target. Conclusions: Millimeter-level margins beyond the GTV significantly impact peripheral normal brain sparing and should be applied with caution. Our model provides a rapid estimate of such an effect, particularly for large and/or irregularly shaped targets

  3. Eldecalcitol normalizes bone turnover markers regardless of their pre-treatment levels.

    Science.gov (United States)

    Shiraki, Masataka; Saito, Hitoshi; Matsumoto, Toshio

    2012-09-01

    Three-year treatment with eldecalcitol has been shown to improve lumbar and total hip bone mineral density (BMD), decrease bone turnover markers, and lower the incidences of vertebral and wrist fractures in patients with osteoporosis more than with treatment with alfacalcidol under vitamin D repletion. The purpose of this study was to determine whether there was a risk of eldecalcitol causing severely suppressed bone turnover in osteoporosis patients with low pre-treatment levels of bone turnover markers. Post-hoc analysis was conducted on the data from a 3-year, randomized, double-blind, active-comparator, clinical trial of eldecalcitol versus alfacalcidol under vitamin D repletion conducted in Japan. Enrolled patients with baseline measurements of bone turnover markers were stratified into tertiles according to their pre-treatment levels of serum bone-specific alkaline phosphatase, serum procollagen type I N-terminal propeptide, or urinary collagen-N-telopeptide. Eldecalcitol treatment rapidly reduced bone turnover markers, and kept them within the normal range. However, in the patients whose baseline values for bone turnover were low, eldecalcitol treatment did not further reduce bone turnover markers during the 3-year treatment period. Further long-term observation may be required to reach the conclusion. CLINICALTRIALS.GOV NUMBER: NCT00144456. Eldecalcitol normalizes, but does not overly suppress, bone turnover regardless of baseline levels of bone turnover markers. Thus, it is unlikely that eldecalcitol treatment will increase the risk of severely suppressed bone turnover and therefore deterioration of bone quality, at least for a treatment duration of 3 years.

  4. Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia.

    Science.gov (United States)

    Abi-Saab, Walid M; Maggs, David G; Jones, Tim; Jacob, Ralph; Srihari, Vinod; Thompson, James; Kerr, David; Leone, Paola; Krystal, John H; Spencer, Dennis D; During, Matthew J; Sherwin, Robert S

    2002-03-01

    Brain levels of glucose and lactate in the extracellular fluid (ECF), which reflects the environment to which neurons are exposed, have never been studied in humans under conditions of varying glycemia. The authors used intracerebral microdialysis in conscious human subjects undergoing electrophysiologic evaluation for medically intractable epilepsy and measured ECF levels of glucose and lactate under basal conditions and during a hyperglycemia-hypoglycemia clamp study. Only measurements from nonepileptogenic areas were included. Under basal conditions, the authors found the metabolic milieu in the brain to be strikingly different from that in the circulation. In contrast to plasma, lactate levels in brain ECF were threefold higher than glucose. Results from complementary studies in rats were consistent with the human data. During the hyperglycemia-hypoglycemia clamp study the relationship between plasma and brain ECF levels of glucose remained similar, but changes in brain ECF glucose lagged approximately 30 minutes behind changes in plasma. The data demonstrate that the brain is exposed to substantially lower levels of glucose and higher levels of lactate than those in plasma; moreover, the brain appears to be a site of significant anaerobic glycolysis, raising the possibility that glucose-derived lactate is an important fuel for the brain.

  5. Circulating levels of carbamylated protein and neutrophil extracellular traps are associated with periodontitis severity in patients with rheumatoid arthritis: A pilot case-control study.

    Science.gov (United States)

    Kaneko, Chihiro; Kobayashi, Tetsuo; Ito, Satoshi; Sugita, Noriko; Murasawa, Akira; Nakazono, Kiyoshi; Yoshie, Hiromasa

    2018-01-01

    An interrelationship between rheumatoid arthritis (RA) and periodontitis has been suggested due to their common pathogenic mechanisms. Protein carbamylation and neutrophil extracellular traps (NETs) formation have been shown to be related to autoimmune conditions, including RA, but their association with periodontitis has not been elucidated. Therefore, we assessed whether or not circulating levels of carbamylated protein (CarP) and NETs are associated with periodontitis severity and influenced by periodontal treatment. We conducted a retrospective case-control study that included 40 patients with RA and periodontitis, 30 patients with periodontitis, and 43 systemically and periodontally healthy controls to assess the circulating levels of CarP and NETs and rheumatologic and periodontal conditions. The same assessments were also performed in 22 patients with RA and periodontitis after 2 months of periodontal treatment, including oral hygiene instruction and full-mouth supragingival scaling. Patients with RA and periodontitis showed significantly higher serum levels of CarP and NETs than the control group (P = 0.04 and P periodontitis. Multiple logistic regression analyses also revealed significantly positive associations between the serum levels of CarP and NETs and moderate to severe periodontitis (P = 0.03 and P = 0.001, respectively). Furthermore, periodontal treatment significantly decreased the serum levels of CarP and NETs in patients with RA and periodontitis (P = 0.03 and P = 0.02). The circulating levels of CarP and NETs are associated with periodontitis severity and influenced by periodontal treatment in patients with RA.

  6. Serum HER 2 extracellular domain level is correlated with tissue HER 2 status in metastatic gastric or gastro-oesophageal junction adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Shu-Qin Dai

    Full Text Available BACKGROUND: To explore the association between serum human epidermal growth factor receptor 2 (HER 2 extracellular domain (ECD levels and tissue HER 2 status in metastatic gastric cancer. PATIENTS AND METHODS: HER 2 status was retrospectively analyzed in 219 advanced gastric or gastroesophageal junction (GEJ patients. Serum HER 2 ECD was measured by chemiluminescent assay and tissue HER 2 was assessed by fluorescent in situ hybridisation (FISH and immunohistochemistry (IHC assay. RESULTS: Significant associations were found between serum HER 2 ECD levels and tissue HER 2 status. Twenty-four patients had HER 2 ECD levels >16.35 ng/mL, which has a sensitivity of 51.4% and a specificity of 97.3% to predict tissue HER 2 status. When the cut-off value was increased to 22 ng/mL, then all 12 patients with serum HER 2 ECD levels>22 ng/mL were tissue HER 2 positive, corresponding to a specificity of 100% and a sensitivity of 32.4%. High serum HER 2 ECD levels were strongly associated with the intestinal histological type (Lauren's classification, liver metastasis, multiple metastasis (>2 and increased LDH levels, but not with overall survival. CONCLUSIONS: The high specificity of the serum HER 2 ECD assay in predicting tissue HER 2 status suggests its potential as a surrogate marker of the HER 2 status in gastric cancer.

  7. Effect of Low-Level Laser Stimulation on EEG Power in Normal Subjects with Closed Eyes

    Directory of Open Access Journals (Sweden)

    Jih-Huah Wu

    2013-01-01

    Full Text Available In a previous study, we found that the low-level laser (LLL stimulation at the palm with a frequency of 10 Hz was able to induce significant brain activation in normal subjects with opened eyes. However, the electroencephalography (EEG changes to LLL stimulation in subjects with closed eyes have not been studied. In the present study, the laser array stimulator was applied to deliver insensible laser stimulations to the palm of the tested subjects with closed eyes (the laser group. The EEG activities before, during, and after the laser stimulation were collected. The EEG amplitude powers of each EEG frequency band at 19 locations were calculated. These power data were then analyzed by SPSS software using repeated-measure ANOVAs and appropriate posthoc tests. We found a pronounced decrease in the EEG power in alpha-bandwidth during laser simulation and then less decrease in the EEG power in delta-bandwidth in normal subjects with laser stimulation. The EEG power in beta-bandwidth in the right occipital area also decreased significantly in the laser group. We suggest that LLL stimulation might be conducive to falling into sleep in patients with sleep problems.

  8. Diet enriched with fresh coconut decreases blood glucose levels and body weight in normal adults.

    Science.gov (United States)

    Vijayakumar, Venugopal; Shankar, Nagashree R; Mavathur, Ramesh; Mooventhan, A; Anju, Sood; Manjunath, N K

    2018-02-20

    Background There exist controversies about the health effects of coconut. Fresh coconut consumption on human health has not been studied substantially. Fresh coconut consumption is a regular part of the diet for many people in tropical countries like India, and thus there is an increasing need to understand the effects of fresh coconut on various aspects of health. Aim To compare the effects of increased saturated fatty acid (SFA) and fiber intake, provided by fresh coconut, versus monounsaturated fatty acid (MUFA) and fiber intake, provided by a combination of groundnut oil and groundnuts, on anthropometry, serum insulin, glucose levels and blood pressure in healthy adults. Materials Eighty healthy volunteers, randomized into two groups, were provided with a standardized diet along with either 100 g fresh coconut or an equivalent amount of groundnuts and groundnut oil for a period of 90 days. Assessments such as anthropometric measurements, blood pressure, blood sugar and insulin levels were performed before and after the supplementation period. Results Results of this study showed a significant reduction in fasting blood sugar (FBS) in both the groups. However, a significant reduction in body weight was observed in the coconut group, while a significant increase in diastolic pressure was observed in the groundnut group. Conclusions Results of this study suggest that fresh coconut-added diet helps reduce blood glucose levels and body weight in normal healthy individuals.

  9. Comparison of Serum Vit D Level Between Psoriasis Patients and Normal Population

    Directory of Open Access Journals (Sweden)

    A. Darjani

    2016-11-01

    Full Text Available Introduction: Psoriasis is a common inflammatory skin disorder with humeral and cellular immune system involvement. On the other hands، Vitamin D has important immunomodulatory effects and its relations with many autoimmune diseases were shown. The relation between Serum Vit D Level and Psoriasis disease remained controversial issue that this study was done to show this relationship. Methods and Materials: In this comparative cross sectional study، 30 psoriatic patients who attended to Razi dermatology clinic in Rasht، by sequential sampling underwent study as case group. 30 healthy people from hospital at the same age، gender and skin-colored also were selected as control group. Inclusion criteria were patients and people without Ca or Vit D supplements usage or underground diseases in relation to hypovitaminosis D. Demographical data were gathered by interviewing and then blood samples from all participants were sent for analysis of serum Ca، P، Vit D and parathormone level. Data analysis was done by SPSS ver. 18 using T-test and Chi 2 test. Result: Mean and SD serum level of Vit D in case and control groups were 25.8± 12.6 ng/ mL and  23.7± 8.9 ng/ mL، respectively (ρ>0.05. Out of all، 24 participants (40% suffered from Vit D Deficiency and 20 people (33.3% from Vit D insufficiency ، only 26.7% study subjects had acceptable serum Vit D level. There were not any significant difference between Vit D deficiency rates and other measured biochemical indices in two groups (36.7% vs. 43.3%. Conclusion: This study showed high level of Vit D deficiency in both psoriatic and normal people that must be notice.

  10. Increased levels of circulating arginase I in overweight compared to normal weight adolescents.

    Science.gov (United States)

    Jung, Christian; Figulla, Hans R; Lichtenauer, Michael; Franz, Marcus; Pernow, John

    2014-02-01

    Overweight and the metabolic syndrome have become major problems, especially in children and adolescents. Obesity at a young age increases the risk for cardiovascular diseases and diabetes mellitus later in life. An early event in the development of cardiovascular disease is endothelial dysfunction which is found in obese young individuals. Increased activity of the enzyme arginase has been described as a central mechanism for endothelial dysfunction, especially in patients with diabetes mellitus. The aim of the study was to determine plasma levels of arginase in overweight adolescents. Sixty-six male German adolescents (age: 15.2 ± 1.1 years old) were included. Thirty-one of them were overweight (>90th age-specific weight percentile). Plasma arginase I and tumor necrosis factor alpha (TNFα) were determined. In addition, clinical data were recorded and anthropometrical measurements of obesity were performed. Overweight adolescents had a higher systolic blood pressure, lower high-density lipoprotein and increased levels of high-sensitive C-reactive protein (CRP). Circulating arginase I was elevated in overweight adolescents (95.8 ± 68.2 ng/ml) compared to normal weight adolescents (39.3 ± 26.9 ng/ml, p obesity. There was no difference between the two groups regarding TNFα. We demonstrate that arginase I levels are increased in obese adolescents. Knowing the important role for arginase in endothelial dysfunction, elevated levels of arginase I may represent a link between obesity, endothelial dysfunction and related comorbidities. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Dermal extracellular lipid in birds.

    Science.gov (United States)

    Stromberg, M W; Hinsman, E J; Hullinger, R L

    1990-01-01

    A light and electron microscopic study of the skin of domestic chickens, seagulls, and antarctic penguins revealed abundant extracellular dermal lipid and intracellular epidermal lipid. Dermal lipid appeared ultrastructurally as extracellular droplets varying from less than 1 micron to more than 25 microns in diameter. The droplets were often irregularly contoured, sometimes round, and of relatively low electron density. Processes of fibrocytes were often seen in contact with extracellular lipid droplets. Sometimes a portion of such a droplet was missing, and this missing part appeared to have been "digested away" by the cell process. In places where cells or cell processes are in contact with fact droplets, there are sometimes extracellular membranous whorls or fragments which have been associated with the presence of fatty acids. Occasionally (in the comb) free fat particles were seen in intimate contact with extravasated erythrocytes. Fat droplets were seen in the lumen of small dermal blood and lymph vessels. We suggest that the dermal extracellular lipid originates in the adipocyte layer and following hydrolysis the free fatty acids diffuse into the epidermis. Here they become the raw material for forming the abundant neutral lipid contained in many of the epidermal cells of both birds and dolphins. The heretofore unreported presence and apparently normal utilization of abundant extracellular lipid in birds, as well as the presence of relatively large droplets of neutral lipid in dermal vessels, pose questions which require a thorough reappraisal of present concepts of the ways in which fat is distributed and utilized in the body.

  12. Large-scale event extraction from literature with multi-level gene normalization.

    Directory of Open Access Journals (Sweden)

    Sofie Van Landeghem

    Full Text Available Text mining for the life sciences aims to aid database curation, knowledge summarization and information retrieval through the automated processing of biomedical texts. To provide comprehensive coverage and enable full integration with existing biomolecular database records, it is crucial that text mining tools scale up to millions of articles and that their analyses can be unambiguously linked to information recorded in resources such as UniProt, KEGG, BioGRID and NCBI databases. In this study, we investigate how fully automated text mining of complex biomolecular events can be augmented with a normalization strategy that identifies biological concepts in text, mapping them to identifiers at varying levels of granularity, ranging from canonicalized symbols to unique gene and proteins and broad gene families. To this end, we have combined two state-of-the-art text mining components, previously evaluated on two community-wide challenges, and have extended and improved upon these methods by exploiting their complementary nature. Using these systems, we perform normalization and event extraction to create a large-scale resource that is publicly available, unique in semantic scope, and covers all 21.9 million PubMed abstracts and 460 thousand PubMed Central open access full-text articles. This dataset contains 40 million biomolecular events involving 76 million gene/protein mentions, linked to 122 thousand distinct genes from 5032 species across the full taxonomic tree. Detailed evaluations and analyses reveal promising results for application of this data in database and pathway curation efforts. The main software components used in this study are released under an open-source license. Further, the resulting dataset is freely accessible through a novel API, providing programmatic and customized access (http://www.evexdb.org/api/v001/. Finally, to allow for large-scale bioinformatic analyses, the entire resource is available for bulk download from

  13. Fructose intake at current levels in the United States may cause gastrointestinal distress in normal adults.

    Science.gov (United States)

    Beyer, Peter L; Caviar, Elena M; McCallum, Richard W

    2005-10-01

    Fructose intake has increased considerably in the United States, primarily as a result of increased consumption of high-fructose corn syrup, fruits and juices, and crystalline fructose. The purpose was to determine how often fructose, in amounts commonly consumed, would result in malabsorption and/or symptoms in healthy persons. Fructose absorption was measured using 3-hour breath hydrogen tests and symptom scores were used to rate subjective responses for gas, borborygmus, abdominal pain, and loose stools. The study included 15 normal, free-living volunteers from a medical center community and was performed in a gastrointestinal specialty clinic. Subjects consumed 25- and 50-g doses of crystalline fructose with water after an overnight fast on separate test days. Mean peak breath hydrogen, time of peak, area under the curve (AUC) for breath hydrogen and gastrointestinal symptoms were measured during a 3-hour period after subjects consumed both 25- and 50-g doses of fructose. Differences in mean breath hydrogen, AUC, and symptom scores between doses were analyzed using paired t tests. Correlations among peak breath hydrogen, AUC, and symptoms were also evaluated. More than half of the 15 adults tested showed evidence of fructose malabsorption after 25 g fructose and greater than two thirds showed malabsorption after 50 g fructose. AUC, representing overall breath hydrogen response, was significantly greater after the 50-g dose. Overall symptom scores were significantly greater than baseline after each dose, but scores were only marginally greater after 50 g than 25 g. Peak hydrogen levels and AUC were highly correlated, but neither was significantly related to symptoms. Fructose, in amounts commonly consumed, may result in mild gastrointestinal distress in normal people. Additional study is warranted to evaluate the response to fructose-glucose mixtures (as in high-fructose corn syrup) and fructose taken with food in both normal people and those with

  14. Increased tenascin C and Toll-like receptor 4 levels in visceral adipose tissue as a link between inflammation and extracellular matrix remodeling in obesity.

    Science.gov (United States)

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Rotellar, Fernando; Valentí, Victor; Silva, Camilo; Gil, María J; Salvador, Javier; Frühbeck, Gema

    2012-10-01

    Obesity is associated with an altered inflammatory and extracellular matrix (ECM) profile. Tenascin C (TNC) is an ECM glycoprotein with proinflammatory effects. We aimed to explore the expression levels of TNC in adipose tissue analyzing the contribution of adipocytes and stromovascular fraction cells (SVFC) as well as its impact on inflammation and ECM regulation. We also analyzed the effect of the stimulation with TNF-α and lipopolysaccharide (LPS) on both SVFC and adipocytes. Samples obtained from 75 subjects were used in the study. Expression levels of TNC, TLR4, MMP2, and MMP9 were analyzed in visceral adipose tissue (VAT) as well as in both adipocytes and SVFC. In addition, Tnc expression was measured in two mice models of obesity. We show, for the first time, that VAT expression levels of TNC are increased in normoglycemic and type 2 diabetic obese patients (Pobese patients with nonalcoholic steatohepatitis (Pobesity were significantly increased (Pexogenous TNC induced (Pobesity via visceral adipose tissue inflammation representing a link with ECM remodeling.

  15. Higher Fasting Plasma Glucose Levels, within the Normal Range, are Associated with Decreased Processing Speed in High Functioning Young Elderly

    OpenAIRE

    Raizes, Meytal; Elkana, Odelia; Franko, Motty; Springer, Ramit Ravona; Segev, Shlomo; Beeri, Michal Schnaider

    2016-01-01

    We explored the association of plasma glucose levels within the normal range with processing speed in high functioning young elderly, free of type 2 diabetes mellitus (T2DM). A sample of 41 participants (mean age = 64.7, SD = 10; glucose 94.5 mg/dL, SD = 9.3), were examined with a computerized cognitive battery. Hierarchical linear regression analysis showed that higher plasma glucose levels, albeit within the normal range (

  16. Balanced levels of nerve growth factor are required for normal pregnancy progression.

    Science.gov (United States)

    Frank, Pierre; Barrientos, Gabriela; Tirado-González, Irene; Cohen, Marie; Moschansky, Petra; Peters, Eva M; Klapp, Burghard F; Rose, Matthias; Tometten, Mareike; Blois, Sandra M

    2014-08-01

    Nerve growth factor (NGF), the first identified member of the family of neurotrophins, is thought to play a critical role in the initiation of the decidual response in stress-challenged pregnant mice. However, the contribution of this pathway to physiological events during the establishment and maintenance of pregnancy remains largely elusive. Using NGF depletion and supplementation strategies alternatively, in this study, we demonstrated that a successful pregnancy is sensitive to disturbances in NGF levels in mice. Treatment with NGF further boosted fetal loss rates in the high-abortion rate CBA/J x DBA/2J mouse model by amplifying a local inflammatory response through recruitment of NGF-expressing immune cells, increased decidual innervation with substance P(+) nerve fibres and a Th1 cytokine shift. Similarly, treatment with a NGF-neutralising antibody in BALB/c-mated CBA/J mice, a normal-pregnancy model, also induced abortions associated with increased infiltration of tropomyosin kinase receptor A-expressing NK cells to the decidua. Importantly, in neither of the models, pregnancy loss was associated with defective ovarian function, angiogenesis or placental development. We further demonstrated that spontaneous abortion in humans is associated with up-regulated synthesis and an aberrant distribution of NGF in placental tissue. Thus, a local threshold of NGF expression seems to be necessary to ensure maternal tolerance in healthy pregnancies, but when surpassed may result in fetal rejection due to exacerbated inflammation. © 2014 Society for Reproduction and Fertility.

  17. Saturation analysis studies of corticosteroid levels in normal Greek subjects and in subjects with haemolytic diseases

    International Nuclear Information System (INIS)

    Vyzantiadis, A.

    1975-07-01

    Between 1970 and 1974 a saturation analysis for cortisol in plasma and free cortisol in urine, and a radioimmunoassay method for aldosterone in plasma and urine were developed. In order to permit a comparative evaluation it was necessary to study corticosteroids, diurnal rhythm and the probable effect of a siesta on this rhythm both in normal subjects and in patients suffering from hemic diseases, in particular from sickle-cell anemia. Saturation assay for cortisol, using serum from pregnant women as source of transcortin, and radioimmunoassay for aldosterone were the basic methods used. Serum cortisol was estimated twice a day (8-9 a.m. and 5-6 p.m.). Cortisol and aldosterone were also estimated in serum and in urine before and after adrenalin stimulation with ACTH. No significant influence of a siesta on the diurnal rhythm of cortisol was observed, nor did the levels of serum cortisol or the diurnal rhythm appear affected in congenital hemolytic anemias, following adrenalin stimulation. The report lists experimental results briefly and refers to a paper in which these are published in more detail

  18. Plasma progranulin and relaxin levels in PCOS women with normal BMI compared to control healthy subjects

    Directory of Open Access Journals (Sweden)

    Samad Akbarzadeh

    2013-09-01

    Full Text Available Background: Poly Cystic Ovary Syndrome (PCOS is the most commonly encountered endocrine gland disease affecting 5-10 present of women at their reproductive age. This syndrome is associated with type 2 diabetes, dyslipidemia, and obesity. Progranulin and relaxin are adipokins that are related with carbohydrate and lipid metabolism. Due to limited data about progranulin and relaxin plasma levels´ in women with PCOS and normal BMI, this study was conducted. Material and Methods: This study is a cross-sectional. During the study 39 women with PCOS and BMI< 25 on the basis of Rotterdam criteria were chosen as the patient group and 38 healthy women were selected as the control group. The concentration of progranulin and relaxin were measured by ELISA technique. Results: The difference in Plasma concentration of progranulin and relaxin, and also some of the biochemical parameters in the patient group versus to the control group was not significant, but there was significant difference in the concentrations of VLDL, triglyceride (p=0.046, insulin (p=0.016, HOMA-IR (p=0.015, testosterone (p=0.01, and DHEAS (p=0.034 in the patients group compared to the control group. Conclusion: In this study, the difference in Plasma concentration of progranulin and relaxin in the patient group compared to the control group was not significant. It could be inferred that lack of change in plasma level of progranulin and relaxin in women with PCOS is related to BMI<25 and FBS<110. Moreoverestosterones, insulin, DHEAS and HOMA-IR changes could be better predictors of PCOS and its associated diabetes.

  19. Impact of Hypertriglyceridemia on Carotid Stenosis Progression under Normal Low-Density Lipoprotein Cholesterol Levels.

    Science.gov (United States)

    Kitagami, Masayuki; Yasuda, Ryuta; Toma, Naoki; Shiba, Masato; Nampei, Mai; Yamamoto, Yoko; Nakatsuka, Yoshinari; Sakaida, Hiroshi; Suzuki, Hidenori

    2017-08-01

    Dyslipidemia is a well-known risk factor for carotid stenosis progression, but triglycerides have attracted little attention. The aim of this study was to assess if serum triglycerides affect progression of carotid stenosis in patients with well-controlled low-density lipoprotein cholesterol (LDL-C) levels. This is a retrospective study in a single hospital consisting of 71 Japanese patients with internal carotid artery stenosis greater than or equal to 50% and normal serum LDL-C levels who underwent angiographic examination with or without the resultant carotid artery stenting or endarterectomy from 2007 to 2011, and were subsequently followed up for 4 years. Clinical factors including fasting serum triglyceride values were compared between the progression (≥10% increase in degree of carotid stenosis on ultrasonography) and the nonprogression groups. During 4 years, 15 patients (21.1%) had carotid stenosis progression on either side. Cox regression analysis demonstrated that symptomatic cases (hazard ratio [HR], 4.327; P = .019), coexisting intracranial arteriosclerotic stenosis (HR, 5.341; P = .005), and hypertriglyceridemia (HR, 6.228; P = .011) were associated with subsequent progression of carotid stenosis. Kaplan-Meier plots demonstrated that the progression-free survival rate was significantly higher in patients without hypertriglyceridemia and intracranial arteriosclerotic stenosis at baseline. Among patients with moderate to severe carotid stenosis and well-controlled LDL-C, hypertriglyceridemia was an important risk factor for progression of carotid stenosis irrespective of surgical treatments. It would be worthwhile to test if triglyceride-lowering medications suppress carotid stenosis progression. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. Clinical characteristics of hepatocellular carcinoma patients with normal serum alpha-fetoprotein level: A study of 112 consecutive cases.

    Science.gov (United States)

    Li, Li; Chen, Jinglong; Xu, Weiran; Ding, Xiaosheng; Wang, Xiangyi; Liang, Jun

    2017-10-26

    Serum alpha-fetoprotein (AFP) level is normal in 30-40% of hepatocellular carcinoma (HCC) patients, and knowledge on its characteristics and clinical outcome is limited. The purpose of this observational study was to determine the clinical presentation, biological behavior and outcome of HCC patients with normal AFP level. Data of 112 consecutive HCC patients with normal AFP level were analyzed retrospectively. Statistical analysis including survival and factors associated with serum AFP level were performed by Kaplan-Meier method and t-test, respectively. Hepatitis B virus infection exited in 83.0% of all 112 HCC patients with normal AFP level. During a mean 52 ± 20 months (range 5-85 months) follow-up, the 1-, 2-, 3-year overall survival (OS) rate was 97.2%, 85.3% and 81.7%, respectively. The OS rates at 3 years stratified by stages at diagnosis were 100%, 96.2%, 85.7%, 11.1% and 0%, respectively for Barcelona Clinic Liver Cancer (BCLC) stage 0-D diseases. Significant difference in OS was observed among patients with BCLC stage 0-D diseases, P level elevated beyond normal figure during follow-up (AFP conversion) in 16 patients, which related with deterioration of liver function, quantitative changes of T helper cell subsets, rapid tumor progression and shorter survival. Patients with sustained normal AFP level had better survival than patients with AFP conversion, P level elevation and the time of AFP elevation to death, P level was relatively optimal. Serum AFP level elevation during follow-up was significantly associated with clinical outcome in terms of OS. © 2017 John Wiley & Sons Australia, Ltd.

  1. Extracellular bioreduction

    Science.gov (United States)

    Chidambaram, Devicharan [Middle Island, NY; Francis, Arokiasamy J [Middle Island, NY

    2012-04-17

    A method for processing environmental or industrial samples to remove, reclaim or otherwise reduce the level of chemical species present in the sample that act as redox active species. The redox active species is kept in a waste chamber and is separated from an aqueous bacterial culture that is held in a culture chamber. The waste chamber and the culture chamber are separated by a porous membrane through which electron transfer can occur but through which the aqueous bacterial culture cannot pass. The redox active species substantially remains in the waste chamber and is in non-contact with the aqueous bacterial culture during the process of removal, reduction or reclamation.

  2. Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

    Science.gov (United States)

    Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

    2005-09-08

    It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

  3. A Neural Signature of Divisive Normalization at the Level of Multisensory Integration in Primate Cortex.

    Science.gov (United States)

    Ohshiro, Tomokazu; Angelaki, Dora E; DeAngelis, Gregory C

    2017-07-19

    Studies of multisensory integration by single neurons have traditionally emphasized empirical principles that describe nonlinear interactions between inputs from two sensory modalities. We previously proposed that many of these empirical principles could be explained by a divisive normalization mechanism operating in brain regions where multisensory integration occurs. This normalization model makes a critical diagnostic prediction: a non-preferred sensory input from one modality, which activates the neuron on its own, should suppress the response to a preferred input from another modality. We tested this prediction by recording from neurons in macaque area MSTd that integrate visual and vestibular cues regarding self-motion. We show that many MSTd neurons exhibit the diagnostic form of cross-modal suppression, whereas unisensory neurons in area MT do not. The normalization model also fits population responses better than a model based on subtractive inhibition. These findings provide strong support for a divisive normalization mechanism in multisensory integration. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Higher Fasting Plasma Glucose Levels, within the Normal Range, are Associated with Decreased Processing Speed in High Functioning Young Elderly.

    Science.gov (United States)

    Raizes, Meytal; Elkana, Odelia; Franko, Motty; Ravona Springer, Ramit; Segev, Shlomo; Beeri, Michal Schnaider

    2016-01-01

    We explored the association of plasma glucose levels within the normal range with processing speed in high functioning young elderly, free of type 2 diabetes mellitus (T2DM). A sample of 41 participants (mean age = 64.7, SD = 10; glucose 94.5 mg/dL, SD = 9.3), were examined with a computerized cognitive battery. Hierarchical linear regression analysis showed that higher plasma glucose levels, albeit within the normal range (levels may have an impact on cognitive function.

  5. High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors.

    Science.gov (United States)

    Koizume, Shiro; Ito, Shin; Yoshioka, Yusuke; Kanayama, Tomohiko; Nakamura, Yoshiyasu; Yoshihara, Mitsuyo; Yamada, Roppei; Ochiya, Takahiro; Ruf, Wolfram; Miyagi, Etsuko; Hirahara, Fumiki; Miyagi, Yohei

    2016-01-01

    Thromboembolic events occur frequently in ovarian cancer patients. Tissue factor (TF) is often overexpressed in tumours, including ovarian clear-cell carcinoma (CCC), a subtype with a generally poor prognosis. TF-coagulation factor VII (fVII) complexes on the cell surface activate downstream coagulation mechanisms. Moreover, cancer cells secrete extracellular vesicles (EVs), which act as vehicles for TF. We therefore examined the characteristics of EVs produced by ovarian cancer cells of various histological subtypes. CCC cells secreted high levels of TF within EVs, while the high-TF expressing breast cancer cell line MDA-MB-231 shed fewer TF-positive EVs. We also found that CCC tumours with hypoxic tissue areas synthesised TF and fVII in vivo, rendering the blood of xenograft mice bearing these tumours hypercoagulable compared with mice bearing MDA-MB-231 tumours. Incorporation of TF into EVs and secretion of EVs from CCC cells exposed to hypoxia were both dependent on the actin-binding protein, filamin-A (filA). Furthermore, production of these EVs was dependent on different protease-activated receptors (PARs) on the cell surface. These results show that CCC cells could produce large numbers of TF-positive EVs dependent upon filA and PARs. This phenomenon may be the mechanism underlying the increased incidence of venous thromboembolism in ovarian cancer patients.

  6. The administration of endocannabinoid uptake inhibitors OMDM-2 or VDM-11 promotes sleep and decreases extracellular levels of dopamine in rats.

    Science.gov (United States)

    Murillo-Rodríguez, Eric; Palomero-Rivero, Marcela; Millán-Aldaco, Diana; Di Marzo, Vincenzo

    2013-01-17

    The family of the endocannabinoid system comprises endogenous lipids (such as anandamide [ANA]), receptors (CB(1)/CB(2) cannabinoid receptors), metabolic enzymes (fatty acid amide hydrolase [FAAH]) and a putative membrane transporter (anandamide membrane transporter [AMT]). Although the role of ANA, FAAH or the CB(1) cannabinoid receptor in sleep modulation has been reported, the effects of the inhibition of AMT on sleep remain unclear. In the present study, we show that microdialysis perfusion in rats of AMT inhibitors, (9Z)-N-[1-((R)-4-hydroxbenzyl)-2-hydroxyethyl]-9-octadecenamide (OMDM-2) or N-(4-hydroxy-2-methylphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (VDM-11; 10, 20 or 30 μM; each compound) delivered into the paraventricular thalamic nucleus (PVA) increased sleep and decreased waking. In addition, the infusion of compounds reduced the extracellular levels of dopamine collected from nucleus accumbens. Taken together, these findings illustrate a critical role of AMT in sleep modulation. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Prognostic significance of hemoglobin level in patients with congestive heart failure and normal ejection fraction.

    Science.gov (United States)

    Varadarajan, Padmini; Gandhi, Siddharth; Sharma, Sanjay; Umakanthan, Branavan; Pai, Ramdas G

    2006-10-01

    Previous studies have shown low hemoglobin (Hb) to have an adverse effect on survival in patients with congestive heart failure (CHF) and reduced left ventricular (LV) ejection fraction (EF); but its effect on survival in patients with CHF and normal EF is not known. This study sought to determine whether low Hb has an effect on survival in patients with both CHF and normal EF. Detailed chart reviews were performed by medical residents on 2,246 patients (48% with normal EF) with a discharge diagnosis of CHF in a large tertiary care hospital from 1990 to 1999. The CHF diagnosis was validated using the Framingham criteria. Mortality data were obtained from the National Death Index. Survival analysis was performed using Kaplan-Meier and Cox regression models. By Kaplan-Meier analysis, low Hb (< 12 gm/dl) compared with normal hemoglobin was associated with a lower 5-year survival in patients with CHF and both normal (38 vs. 50%, p = 0.0008) and reduced (35 vs. 48%, p = 0.0009) EF. Using the Cox regression model, low Hb was an independent predictor of mortality after adjusting for age, gender, renal dysfunction, diabetes mellitus, hypertension, and EF in both groups of patients. Low Hb has an independent adverse effect on survival in patients with CHF and both normal and reduced EF in both groups of patients.

  8. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Langsted, A.; Freiberg, J.J.; Nordestgaard, Børge

    2008-01-01

    BACKGROUND: Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events. METHODS AND RESULTS: We cross-sectionally studied 33 391 individuals 20 to 95...... to HDL cholesterol, and ratio of apolipoprotein B to apolipoprotein A1 did not change in response to normal food intake. The maximum changes after normal food and fluid intake from fasting levels were -0.2 mmol/L for total cholesterol, -0.2 mmol/L for low-density lipoprotein cholesterol, -0.1 mmol...... years of age from the Copenhagen General Population Study. We also studied 9319 individuals 20 to 93 years of age from the Copenhagen City Heart Study, 1166 of whom developed cardiovascular events during 14 years of follow-up. Compared with fasting levels, total cholesterol, low-density lipoprotein...

  9. Effects of synthetic TRH on plasma human prolactin levels in normal subjects and in patients with various endocrine disorders

    International Nuclear Information System (INIS)

    Ogawa, Norio; Miyoshi, Masanori; Suzuki, Shinya; Ofuji, Tadashi; Furuno, Katsushi

    1974-01-01

    HPRL was iodinated a modification of the enzymatic method using lactoperoxidase. By solid-phase RIA using antibody-coated disposable plastic microtiter trays, it was confirmed that the second peak consisted of the immunoreactive material that was used for RIA. For the measurement of plasma hPRL levels, the double antibody technique was used to separate bound from free labeled hormones. Basal plasma hPRL levels in normal subjects were less than 20 ng/ml. The mean basal hPRL levels were 10.2 +- 4.9 (Mean+-SD) ng/ml in 13 normal men and 9.6+-5.4 ng/ml in 8 normal women; no statistically significant sex difference was observed. When synthetic TRH was administered intravenously to a normal male subject, the maximum increase in plasma hPRL above the baseline level increased linearly as a function of the log of the TRH dose between 25 and 100 μg of TRH. Intravenous administration of 500 μg of TRH caused a significant increase in plasma hPRL in all of the 10 normal subjects tested. Plasma hPRL levels in 2 patients with Sheehan's syndrome and in a patient with operated-irradiated chromophobe adenoma tended to be low, and they showed no significant increase in plasma hPRL after TRH injection. Basal plasma hPRL levels in most of the patients with hypothalamopituitary tumor tended to be high. Plasma hPRL levels were normal in most patients with pituitary dwarfism. Plasma hPRL levels in 2 patients with hyperthyroidism tended to be low, and they showed no significant hPRL response to TRH, while patients with hypothyroidism showed normal or rather exaggerated hPRL response to TRH. Plasma hPRL levels were normal in most of the patients with Cushing's syndrome and plasma hPRL responses to TRH in these patients were normal. TRH-induced hPRL secretion tended to be impaired in patients receiving long-term and high doses of glucocorticoid. (auth.)

  10. Physical activity levels of normal-weight and overweight girls and boys during primary school recess.

    Science.gov (United States)

    Stratton, Gareth; Ridgers, Nicola D; Fairclough, Stuart J; Richardson, David J

    2007-06-01

    This study aimed to compare moderate-to-vigorous physical activity (MVPA) and vigorous physical activity (VPA) in normal-weight and overweight boys and girls during school recess. Four hundred twenty children, age 6 to 10 years, were randomly selected from 25 schools in England. Three hundred seventy-seven children completed the study. BMI was calculated from height and weight measurements, and heart rate reserve thresholds of 50% and 75% reflected children's engagement in MVPA and VPA, respectively. There was a significant main effect for sex and a significant interaction between BMI category and sex for the percent of recess time spent in MVPA and VPA. Normal-weight girls were the least active group, compared with overweight boys and girls who were equally active. Fifty-one boys and 24 girls of normal weight achieved the 40% threshold; of these, 30 boys and 10 girls exceeded 50% of recess time in MVPA. Eighteen overweight boys and 22 overweight girls exceeded the 40% threshold, whereas 8 boys and 8 girls exceeded the 50% threshold. Overweight boys were significantly less active than their normal-weight male counterparts; this difference did not hold true for girls. Even though nearly double the number of normal-weight children achieved the 40% of MVPA during recess compared with overweight children, physical activity promotion in school playgrounds needs to be targeted not only at overweight but at other health parameters, as 40 overweight children met the 40% MVPA target proposed for recess.

  11. Extracellular Na+ levels regulate formation and activity of the NaX/alpha1-Na+/K+-ATPase complex in neuronal cells.

    Directory of Open Access Journals (Sweden)

    Emmanuelle eBerret

    2014-12-01

    Full Text Available MnPO neurons play a critical role in hydromineral homeostasis regulation by acting as sensors of extracellular sodium concentration ([Na+]out. The mechanism underlying Na+-sensing involves Na+-flow through the NaX channel, directly regulated by the Na+/K+-ATPase α1-isoform which controls Na+-influx by modulating channel permeability. Together, these two partners form a complex involved in the regulation of intracellular sodium ([Na+]in. Here we aim to determine whether environmental changes in Na+ could actively modulate the NaX/Na+/K+-ATPase complex activity.We investigated the complex activity using patch-clamp recordings from rat MnPO neurons and Neuro2a cells. When the rats were fed with a high-salt-diet, or the [Na+] in the culture medium was increased, the activity of the complex was up-regulated. In contrast, drop in environmental [Na+] decreased the activity of the complex. Interestingly under hypernatremic condition, the colocalization rate and protein level of both partners were up-regulated. Under hyponatremic condition, only NaX protein expression was increased and the level of NaX/Na+/K+-ATPase remained unaltered. This unbalance between NaX and Na+/K+-ATPase pump proportion would induce a bigger portion of Na+/K+-ATPase-control-free NaX channel. Thus we suggest that hypernatremic environment increases NaX/Na+/K+-ATPase α1-isoform activity by increasing the number of both partners and their colocalization rate, whereas hyponatremic environment down-regulates complex activity via a decrease in the relative number of NaX channels controlled by the pump.

  12. IGF-1R Regulates the Extracellular Level of Active MMP-2, Pathological Neovascularization, and Functionality in Retinas of OIR Mouse Model.

    Science.gov (United States)

    Lorenc, Valeria E; Subirada Caldarone, Paula V; Paz, María C; Ferrer, Darío G; Luna, José D; Chiabrando, Gustavo A; Sánchez, María C

    2018-02-01

    In ischemic proliferative diseases such as retinopathies, persistent hypoxia leads to the release of numerous neovascular factors that participate in the formation of abnormal vessels and eventually cause blindness. The upregulation and activation of metalloproteinases (MMP-2 and MMP-9) represent a final common pathway in this process. Although many regulators of the neovascular process have been identified, the complete role of the insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) appears to be significantly more complex. In this study, we used an oxygen-induced retinopathy (OIR) mouse model as well as an in vitro model of hypoxia to study the role of MMP-2 derived from Müller glial cells (MGCs) and its relation with the IGF-1/IGF-1R system. We demonstrated that MMP-2 protein expression increased in P17 OIR mice, which coincided with the active phase of the neovascular process. Also, glutamine synthetase (GS)-positive cells were also positive for MMP-2, whereas IGF-1R was expressed by GFAP-positive cells, indicating that both proteins were expressed in MGCs. In addition, in the OIR model a single intravitreal injection of the IGF-1R blocking antibody (αIR3) administered at P12 effectively prevented pathologic neovascularization, accelerated physiological revascularization, and improved retinal functionality at P17. Finally, in MGC supernatants, the blocking antibody abolished the IGF-1 effect on active MMP-2 under normoxic and hypoxic conditions without affecting the extracellular levels of pro-MMP-2. These results demonstrate, for the first time, that the IGF-1/IGF-1R system regulates active MMP-2 levels in MGCs, thus contributing to MEC remodeling during the retinal neovascular process.

  13. Basic conditions for radioimmunoassay of erythropoietin, and plasma levels of erythropoietin in normal subjects and anemic patients

    Energy Technology Data Exchange (ETDEWEB)

    Mizoguchi, Hideaki; Ohta, Kazuo; Suzuki, Toshiaki; Murakami, Akihiko; Ueda, Masatsugu; Sasaki, Ryuzou; Chiba, Hideo

    1987-02-01

    We have developed a specific and sensitive radioimmunoassay for erythropoietin. The sensitivity of our assay is 0.5 mU or 5 mU/ml and is sufficient to detect normal plasma erythropoietin levels. The mean plasma erythropoietin titer of normal Japanese with our radioimmunoassay was found to be 21.9 +- 12.0 mU/ml (n = 199). The validity of the method was further confirmed by the observations that the plasma erythropoietin titers were inversely related to hemoglobin levels in patients with nonuremic anemias, lower in uremic patients than in patients with nonuremic anemias with similar hemoglobin levels, markedly elevated in patients with aplastic anemia and pure red cell aplasia, and in a low normal range in patients with polycythemia vera.

  14. Normal cholesterol levels with lovastatin (Mevinolin) therapy in a child with homozygous familial hypercholesterolemia following liver transplantation

    International Nuclear Information System (INIS)

    East, C.; Grundy, S.M.; Bilheimer, D.W.

    1986-01-01

    Patients with homozygous familial hypercholesterolemia produce no normal low-density lipoprotein (LDL) receptors, and as a result, LDL accumulates in plasma, causing severe premature atherosclerosis. Two years ago, liver transplantation was performed in a child with homozygous familial hypercholesterolemia, restoring LDL receptor activity to about 60% of normal and reducing the LDL cholesterol level by 81%. However, the patient's lipoprotein levels remained significantly elevated for her age and sex. Treatment with lovastatin (mevinolin) one year after transplantation produced a marked improvement in the patient's lipoprotein profile. The total and LDL cholesterol levels fell 40% and 49%, respectively, to values within the normal range. The level of very low-density lipoprotein cholesterol fell 41%, and the level of total triglycerides declined 28%. While lovastatin therapy decreased the production rate of LDL by 35%, it did not affect the LDL fractional clearance rate. Thus, the combination of liver transplantation and lovastatin restored total and LDL cholesterol levels to normal in this patient with homozygous familial hypercholesterolemia

  15. Vasopressin and oxytocin levels during normal pregnancy: effects of chronic dietary sodium restriction

    NARCIS (Netherlands)

    van der Post, J. A.; van Buul, B. J.; Hart, A. A.; van Heerikhuize, J. J.; Pesman, G.; Legros, J. J.; Steegers, E. A.; Swaab, D. F.; Boer, K.

    1997-01-01

    Neurohypophysial hormones are thought to be involved in alterations in fluid balance during pregnancy and delivery. In the course of normal pregnancy intravascular volume is increased whereas sodium restriction is thought to reduce plasma volume and cardiac output. In the present study, we measured

  16. Thyroid storm with multiple organ failure, disseminated intravascular coagulation, and stroke with a normal serum FT3 level.

    Science.gov (United States)

    Harada, Yuko; Akiyama, Hisanao; Yoshimoto, Tatsuji; Urao, Yasuko; Ryuzaki, Munekazu; Handa, Michiko

    2012-01-01

    Thyroid storm is a rare disorder with a sudden onset, rapid progression and high mortality. We experienced a case of thyroid storm which had a devastating course, including multiple organ failure (MOF), severe hypoglycemia, disseminated intravascular coagulation (DIC), and stroke. It was difficult to make a diagnosis of thyroid storm in the present patient, because she did not have a history of thyroid disease and her serum FT3 level was normal. Clinicians should be aware that thyroid storm can occur even when there is an almost normal level of thyroid hormones, and that intensive anticoagulation is required for patients with atrial fibrillation to prevent stroke after thyroid storm.

  17. High Normal Uric Acid Levels Are Associated with an Increased Risk of Diabetes in Lean, Normoglycemic Healthy Women.

    Science.gov (United States)

    Shani, Michal; Vinker, Shlomo; Dinour, Dganit; Leiba, Merav; Twig, Gilad; Holtzman, Eliezer J; Leiba, Adi

    2016-10-01

    The risk associated with serum uric acid (SUA) levels within the normal range is unknown, especially among lean and apparently healthy adults. Evaluating whether high-normal SUA levels, 6.8 mg/dL and below, are associated with an increased diabetes risk, compared with low-normal SUA. This was a cohort study with 10 years of followup involving all clinics of the largest nationally distributed Health Maintenance Organization in Israel. Participants included 469,947 examinees, 40-70 years old at baseline, who had their SUA measured during 2002. We excluded examinees who had hyperuricemia (SUA > 6.8 mg/dL), impaired fasting glucose, overweight or obesity and chronic cardiovascular or renal disorders. The final cohort was composed of 30 302 participants. Participants were followed up to a new diagnosis of diabetes during the study period. Odds ratio of developing diabetes among participants with high-normal baseline SUA were compared with low-normal (2 ≤ uric acid lean women when compared with those with low-normal values.

  18. Cutoff Values of Serum Carcinoembryonic Antigen (CEA) in Normal Korean Adults and Factors Influencing Serum CEA Level

    International Nuclear Information System (INIS)

    Kim, Jong Soon; Kim, Sun Wook; Chung, June Key; Lee, Dong Soo

    1994-01-01

    Carcinoembryonic Antigen is one of most frequently checked tumor markers in cancer management. We performed statistical analysis with serum CEA data of 2626 persons who received regular health examination and were thought to be free of active disease to determine the cutoff values of serum CEA level in normal Korean adults and to study the factors influencing serum CEA levels in normal subjects. 1) The cutoff values of serum CEA in normal Korean adults in general were 9.28 ng/ml for men, 5.90 ng/ml for women. 2) Serum CEA level was influenced by age, present smoking history, sex, and abnormal findings in chest X ray. 3) Serum CEA level had no correlation with the history of amount of alcohol consumption or obesity. 4) Cutoff values of serum CEA in normal Korean adults were tabulated according to age, sex, and smoking history. Serum CEA level was influenced by age, sex, present smoking history and abnormal findings in chest X ray and cutoff values of serum CEA were tabulated according to age, sex, and smoking history.

  19. Pathogenesis of fever: effects of various endogenous pyrogens upon the level of circulating granulocytes in normal rabbits.

    Science.gov (United States)

    KING, M K

    1960-11-01

    The endogenous pyrogen in the serum or plasma of rabbits 2 hours after the intravenous injection of typhoid vaccine had a marked effect on the circulating leucocytes of normal rabbits. Immediately following intravenous injection there was a brief, but marked, granulocytopenia which was quickly followed by a granulocytosis. Under the same circumstances pooled heterologous serum or plasma from normal rabbits produced no fever or significant change in the level of circulating leucocytes. The cell-free fluid of sterile peritoneal exudates produced a marked leucocytosis without a preceding leucopenia when injected intravenously into normal rabbits. When comparably pyrogenic doses of typhoid vaccine were injected in the same manner no significant change in the level of circulating leucocytes occurred. The relevance of these findings to the pathogenesis of fever is discussed.

  20. Comparison of blood lead levels of mothers and cord blood in intrauterine growth retarded neonates and normal term neonates

    International Nuclear Information System (INIS)

    Iranpour, R.; Besharati, Amir A.; Nasseri, F.; Hashemipour, M.; Kelishadi, R.; Balali-Mood, M.

    2007-01-01

    Objective was to compare the blood lead levels of mothers and cord blood in intrauterine growth retarded (IUGR) neonates and normal term neonates. From April 2005, we carried out a cross-sectional, prospective study in Isfahan University of Medical Sciences, Isfahan, Iran. Blood lead levels were measured in the umbilical cord and maternal venous blood samples in the 32 mother-infant pairs with IUGR full term neonates and 34 mother-infant pairs with normal full term neonates. Blood-lead levels were analyzed by atomic absorption spectrometry. The mean lead concentration in neonates of IUGR and normal groups was not significantly different (107.47+- 16.75 versus 113.08+-19.08 ug/L, p=0.2). The mean lead concentration in mothers of IUGR group was lower than normal groups, but this difference was not significant (124.56+-19.71 versus 135.26+-26.91 ug/L, p=0.07). Maternal lead levels were strongly related with related with cord blood in both IUGR and normal groups (r=0.8, p 100ug/L by the centers for disease control; however, this was not statistically different between the groups. Our results indicate that the mean lead level was not higher in IUGR neonates, and the whole blood lead was not related to the birth weight. In addition, maternal and cord blood lead levels were strongly correlated, and there were remarkable lead burdens on both the mothers and their neonates in this industrial area. (author)

  1. Effect of Luffa aegyptiaca (seeds) and Carissa edulis (leaves) extracts on blood glucose level of normal and streptozotocin diabetic rats.

    Science.gov (United States)

    El-Fiky, F K; Abou-Karam, M A; Afify, E A

    1996-01-01

    The present study investigates the effect of oral administration of the ethanolic extracts of Luffa aegyptiaca (seeds) and Carissa edulis (leaves) on blood glucose levels both in normal and streptozotocin (STZ) diabetic rats. Treatment with both extracts significantly reduced the blood glucose level in STZ diabetic rats during the first three hours of treatment. L. aegyptiaca extract decreased blood glucose level with a potency similar to that of the biguanide, metformin. The total glycaemic areas were 589.61 +/- 45.62 mg/dl/3 h and 660.38 +/- 64.44 mg/dl/3 h for L. aegyptiaca and metformin, respectively, vs. 816.73 +/- 43.21 mg/dl/3 h for the control (P < 0.05). On the other hand, in normal rats, both treatments produced insignificant changes in blood glucose levels compared to glibenclamide treatment.

  2. Extracellular matrix structure.

    Science.gov (United States)

    Theocharis, Achilleas D; Skandalis, Spyros S; Gialeli, Chrysostomi; Karamanos, Nikos K

    2016-02-01

    Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Insulin-like factor 3 serum levels in 135 normal men and 85 men with testicular disorders

    DEFF Research Database (Denmark)

    Bay, K; Hartung, S; Ivell, R

    2005-01-01

    Insulin-like factor 3 (INSL3) serum levels were measured in 135 andrologically well-characterized normal men and 85 patients with testicular disorders to investigate how the hormone, which is a major secretory product of human Leydig cells, is related to testosterone (T), LH, and semen quality. I...

  4. A Look at the Memory Performance of Retarded and Normal Children Utilizing the Levels of Processing Framework.

    Science.gov (United States)

    Lupart, Judy L.; Mulcahy, Robert F.

    Memory performance differences of mental age matched (9-12 years) educable mentally retarded (EMR) (n=56) and normal (n=56) children were examined in two experiments using the F. Craik and R. Lockhart levels of processing framework. In experiment 1, Ss were randomly assigned to an incidental, intentional, or planned intentional learning condition,…

  5. N-Acetylcysteine Normalizes Glutamate Levels in Cocaine-Dependent Patients: A Randomized Crossover Magnetic Resonance Spectroscopy Study

    NARCIS (Netherlands)

    Schmaal, Lianne; Veltman, Dick J.; Nederveen, Aart; van den Brink, Wim; Goudriaan, Anna E.

    2012-01-01

    Treatment with N-acetylcysteine (NAC) normalizes glutamate (Glu) homeostasis and prevents relapse in drug-dependent animals. However, the effect of NAC on brain Glu levels in substance-dependent humans has not yet been investigated. Proton magnetic resonance spectroscopy (H-1 MRS) was used to

  6. N-Acetylcysteine Normalizes Glutamate Levels in Cocaine-Dependent Patients: A Randomized Crossover Magnetic Resonance Spectroscopy Study

    NARCIS (Netherlands)

    Schmaal, L.; Veltman, D.J.; Nederveen, A.; van den Brink, W.; Goudriaan, A.E.

    2012-01-01

    Treatment with N-acetylcysteine (NAC) normalizes glutamate (Glu) homeostasis and prevents relapse in drug-dependent animals. However, the effect of NAC on brain Glu levels in substance-dependent humans has not yet been investigated. Proton magnetic resonance spectroscopy (1 H MRS) was used to

  7. Children with severe Osteogenesis imperfecta and short stature present on average with normal IGF-I and IGFBP-3 levels.

    Science.gov (United States)

    Hoyer-Kuhn, Heike; Höbing, Laura; Cassens, Julia; Schoenau, Eckhard; Semler, Oliver

    2016-07-01

    Osteogenesis imperfecta (OI) is characterized by bone fragility and short stature. Data about IGF-I/IGFBP-3 levels are rare in OI. Therefore IGF-I/IGFBP-3 levels in children with different types of OI were investigated. IGF-I and IGFBP-3 levels of 60 children (male n=38) were assessed in a retrospective cross-sectional setting. Height/weight was significant different [height z-score type 3 versus type 4: p=0.0011 and weight (p≤0.0001)] between OI type 3 and 4. Mean IGF-I levels were in the lower normal range (mean±SD level 137.4±109.1 μg/L). Mean IGFBP-3 measurements were in the normal range (mean±SD 3.105±1.175 mg/L). No significant differences between OI type 3 and 4 children have been observed (IGF-I: p=0.0906; IGFBP-3: p=0.2042). Patients with different severities of OI have IGF-I and IGFBP-3 levels in the lower normal range. The type of OI does not significantly influence these growth factors.

  8. Immunoconglutinin levels in normal and diseased population groups in Southern Africa

    Science.gov (United States)

    Watson, K. C.

    1971-01-01

    Immunoconglutinin (I-K) levels were measured in adult blood donors of European and African origin and in patients with the following diseases: acute typhoid fever, amoebic liver abscess, chronic liver disease and primary hepatoma. The lowest levels were found in the white donor group and the highest in those with chronic liver disease and those with primary hepatoma. African donors had levels higher than white donors which may relate to chronic infection and particularly chronic parasitic infestation. There was poor correlation between `O' and `H' antibodies and I-K levels in the typhoid group. In those with chronic liver disease there was some correlation between I-K levels and total γ-globulin and also with raised IgM and IgA levels but not with raised IgG. PMID:4103887

  9. Insulin Resistance and Serum Levels of Interleukin-17 and Interleukin-18 in Normal Pregnancy

    OpenAIRE

    Jahromi, Abdolreza Sotoodeh; Shojaei, Mohammad; Ghobadifar, Mohamed Amin

    2014-01-01

    We performed this study to evaluate the role of Interleukin-17 (IL-17) and Interleukin-18 (IL-18) in insulin resistance during normal pregnancy. This descriptive cross sectional study was carried out on 97 healthy pregnant women including 32, 25, and 40 individuals in the first, second, and third trimesters, respectively, and on 28 healthy non pregnant women between the autumn of 2012 and the spring of 2013. We analyzed the serum concentrations of IL-17 and IL-18 by using the enzyme linked im...

  10. A case of moderate liver enzyme elevation after acute acetaminophen overdose despite undetectable acetaminophen level and normal initial liver enzymes.

    Science.gov (United States)

    Bebarta, Vikhyat S; Shiner, Drew C; Varney, Shawn M

    2014-01-01

    Liver function test (LFT) increase is an early sign of acetaminophen (APAP) toxicity. Typically, when an acute overdose patient is evaluated and has an initial undetectable APAP level and normal liver enzymes, the patient is not treated with N-acetylcysteine, and liver enzymes are not expected to increase later. We report a case of moderate LFT increase despite normal LFTs and an undetectable APAP level after delayed presentation of an APAP ingestion. A 22-year-old male with no medical history ingested 15-25 hydrocodone/APAP tablets (5 mg/500 mg). His suicide note and his bunkmate corroborated the overdose time. He arrived at the emergency department 16 hours after ingestion. At that time, his APAP level was enzymes were normal [aspartate transaminase (AST) 31 U/L and alanine transaminase (ALT) 34 U/L]. Twenty-nine hours after ingestion, the psychiatry team obtained LFTs (AST 45, ALT 61). He had persistent nausea and diffuse abdominal pain. On repeat analysis, the APAP level at 36 hours was found to be <10 μg/mL, AST 150, and ALT 204. After 2 more days of increasing LFTs and persistent abdominal pain and nausea, the toxicology department was consulted, the patient was transferred to the medicine department, and intravenous N-acetylcysteine was started 66 hours after ingestion. He was treated for 16 hours and had a significant decline in LFTs and symptom resolution. His prothrombin time, bilirubin, lactate, creatinine, and mental status were normal throughout the admission. Other cases of LFT increase were excluded. Our case report illustrates that a moderate increase in liver transaminase may occur despite an initial undetectable APAP level and normal transaminases after a delayed presentation. In our case, no serious clinical effects were reported.

  11. [Prevalence of dyslipidemia and normal blood lipids level in Uygur population in Kashgar area of Xinjiang Uygur Autonomous Region].

    Science.gov (United States)

    Zhang, Z B; Xue, Z X; Wu, X J; Wang, T M; Li, Y H; Song, X L; Chao, X F; Wang, G; Nazibam, Nurmamat; Ayxamgul, Bawudun; Gulbahar, Elyas; Zhou, Z Y; Sun, B S; Wang, Y Z; Wang, M

    2017-06-10

    Objective: To understand the prevalence of dyslipidemia and normal blood lipids level in Uygur diabetes patients in Kashgar prefecture in southern area of Xinjiang. Methods: A total of 5 078 local residents aged ≥18 years (42.56 % were men) selected through cluster random sampling in Kashgar were surveyed by means of questionnaire survey, physical examination and laboratory test, and 521 diabetes patients were screened. Results: The overall prevalence of dyslipidemia in diabetes patients was 59.50 % (310/521) with adjusted rate as 49.39 % . Age ≥65 years, overweight, obesity and abdominal obesity increased the risk for dyslipidemia by 0.771 times (95 % CI : 1.015-3.088), 1.132 times (95 % CI : 1.290-3.523), 1.688 times (95 % CI : 1.573-4.592) and 0.801 times (95 % CI : 1.028-3.155) respectively. Compared with males, female was a protective factor for dyslipidemia ( OR =0.507, 95 %CI : 0.334-0.769). The overall normal rate of blood lipids level including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) for type 2 diabetes patients was 11.13 % . Female, higher BMI and abdominal obesity were the factors influencing the overall normal blood lipids level. The normal rate of LDL-C level decreased with increase of age, BMI and waist circumferences (trend test χ (2)=18.049, P dyslipidemia in Uygur diabetes patients in Kashgar was high, however, the overall normal rate of blood lipid level was relatively low. Obesity was the most important risk factor for dyslipidemia in this area. More attention should be paid to dyslipidemia prevention in women.

  12. Multiple chromosome aberrations among newborns from high level natural radiation area and normal level natural radiation area of south west coast of Kerala

    International Nuclear Information System (INIS)

    Soren, D.C.; Ramachandran, E.N.; Karuppasamy, C.V.; Cheriyan, V.D.; Anil Kumar, V.; Koya, P.K.M.; Seshadri, M.

    2010-01-01

    Cord blood samples were collected in heparin vials and microculture techniques employed to obtain good metaphase chromosome spreads. In cytogenetic studies on newborns cells with multiple aberrations were recorded in 57 from a total of 27285 newborns (1266972 cells). Of these 17294 newborns (964140 cells) were from High Level Natural Radiation Area (HLNRA) and 9991 newborns (302832 cells) from Normal Level Natural Radiation Area (NLNRA). Cells with multiple aberrations were observed in 38 and 19 newborns from High and Normal Level Natural Radiation Area respectively. On an average one cell with multiple aberrations was observed among 479 newborns. Cells with multiple aberrations were observed in newborns from HLNRA as well as NLNRA in both males and females. Gender difference of newborns, maternal age group and background radiation levels did not seem to have any influence in the occurrence of Multiple chromosome aberrations

  13. Insulin resistance and serum levels of interleukin-17 and interleukin-18 in normal pregnancy.

    Science.gov (United States)

    Jahromi, Abdolreza Sotoodeh; Shojaei, Mohammad; Ghobadifar, Mohamed Amin

    2014-06-01

    We performed this study to evaluate the role of Interleukin-17 (IL-17) and Interleukin-18 (IL-18) in insulin resistance during normal pregnancy. This descriptive cross sectional study was carried out on 97 healthy pregnant women including 32, 25, and 40 individuals in the first, second, and third trimesters, respectively, and on 28 healthy non pregnant women between the autumn of 2012 and the spring of 2013. We analyzed the serum concentrations of IL-17 and IL-18 by using the enzyme linked immunosorbent assay (ELISA). Insulin resistance was measured by homeostasis model assessment of insulin resistance equation. No significant differences between the demographic data of the pregnant and non pregnant groups were observed. Insulin resistant in pregnant women was significantly higher than the controls (p=0.006). Serum IL-17 concentration was significantly different in non pregnant women and pregnant women in all gestational ages (ppregnant women (pinsulin resistance (r=0.08, p=0.34 vs. r=0.01, p=0.91, respectively). Our data suggested that IL-17 and IL-18 do not appear to attribute greatly to pregnancy deduced insulin resistance during normal pregnancy.

  14. Cognitive levels of performance account for hemispheric lateralisation effects in dyslexic and normally reading children.

    Science.gov (United States)

    Heim, Stefan; Grande, Marion; Meffert, Elisabeth; Eickhoff, Simon B; Schreiber, Helen; Kukolja, Juraj; Shah, Nadim Jon; Huber, Walter; Amunts, Katrin

    2010-12-01

    Recent theories of developmental dyslexia explain reading deficits in terms of deficient phonological awareness, attention, visual and auditory processing, or automaticity. Since dyslexia has a neurobiological basis, the question arises how the reader's proficiency in these cognitive variables affects the brain regions involved in visual word recognition. This question was addressed in two fMRI experiments with 19 normally reading children (Experiment 1) and 19 children with dyslexia (Experiment 2). First, reading-specific brain activation was assessed by contrasting the BOLD signal for reading aloud words vs. overtly naming pictures of real objects. Next, ANCOVAs with brain activation during reading the individuals' scores for all five cognitive variables assessed outside the scanner as covariates were performed. Whereas the normal readers' brain activation during reading showed co-variation effects predominantly in the right hemisphere, the reverse pattern was observed for the dyslexics. In particular, middle frontal gyrus, inferior parietal cortex, and precuneus showed contralateral effects for controls as compared to dyslexics. In line with earlier findings in the literature, these data hint at a global change in hemispheric asymmetry during cognitive processing in dyslexic readers, which, in turn, might affect reading proficiency. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Normal Theory Two-Stage ML Estimator When Data Are Missing at the Item Level.

    Science.gov (United States)

    Savalei, Victoria; Rhemtulla, Mijke

    2017-08-01

    In many modeling contexts, the variables in the model are linear composites of the raw items measured for each participant; for instance, regression and path analysis models rely on scale scores, and structural equation models often use parcels as indicators of latent constructs. Currently, no analytic estimation method exists to appropriately handle missing data at the item level. Item-level multiple imputation (MI), however, can handle such missing data straightforwardly. In this article, we develop an analytic approach for dealing with item-level missing data-that is, one that obtains a unique set of parameter estimates directly from the incomplete data set and does not require imputations. The proposed approach is a variant of the two-stage maximum likelihood (TSML) methodology, and it is the analytic equivalent of item-level MI. We compare the new TSML approach to three existing alternatives for handling item-level missing data: scale-level full information maximum likelihood, available-case maximum likelihood, and item-level MI. We find that the TSML approach is the best analytic approach, and its performance is similar to item-level MI. We recommend its implementation in popular software and its further study.

  16. Normal Morning MCH Levels and No Association with REM or NREM Sleep Parameters in Narcolepsy Type 1 and Type 2

    DEFF Research Database (Denmark)

    Schrölkamp, Maren; Jennum, Poul J; Gammeltoft, Steen

    2017-01-01

    in rapid eye movement (REM) and nonrapid eye movement (NREM) sleep regulation. Hypocretin neurons reciprocally interact with MCH neurons. We hypothesized that altered MCH secretion contributes to the symptoms and sleep abnormalities of narcolepsy and that this is reflected in morning cerebrospinal fluid...... MCH levels. CONCLUSION: Our study shows that MCH levels in CSF collected in the morning are normal in narcolepsy and not associated with the clinical symptoms, REM sleep abnormalities, nor number of muscle movements during REM or NREM sleep of the patients. We conclude that morning lumbar CSF MCH......STUDY OBJECTIVES: Other than hypocretin-1 (HCRT-1) deficiency in narcolepsy type 1 (NT1), the neurochemical imbalance of NT1 and narcolepsy type 2 (NT2) with normal HCRT-1 levels is largely unknown. The neuropeptide melanin-concentrating hormone (MCH) is mainly secreted during sleep and is involved...

  17. Acromegaly with Normal Insulin-Like Growth Factor-1 Levels and Congestive Heart Failure as the First Clinical Manifestation

    Directory of Open Access Journals (Sweden)

    Hyae Min Lee

    2015-09-01

    Full Text Available The leading cause of morbidity and mortality in patients with acromegaly is cardiovascular complications. Myocardial exposure to excessive growth hormone can cause ventricular hypertrophy, hypertension, arrhythmia, and diastolic dysfunction. However, congestive heart failure as a result of systolic dysfunction is observed only rarely in patients with acromegaly. Most cases of acromegaly exhibit high levels of serum insulin-like growth factor-1 (IGF-1. Acromegaly with normal IGF-1 levels is rare and difficult to diagnose. Here, we report a rare case of an acromegalic patient whose first clinical manifestation was severe congestive heart failure, despite normal IGF-1 levels. We diagnosed acromegaly using a glucose-loading growth hormone suppression test. Cardiac function and myocardial hypertrophy improved 6 months after transsphenoidal resection of a pituitary adenoma.

  18. Effect of passive smoking on the levels of pregnancy associated plasma protein-A in normal rats

    International Nuclear Information System (INIS)

    Naveed, A.K.; Rahim, A.; Malik, M.S.

    2010-01-01

    To measure the levels of pregnancy associated plasma protein- A (PAPPA-A) in normal rats exposed to cigarette smoke. Sixty albino rats of Sprague- Dawley strain weighing 200-250 gm, divided into two groups. Both the groups were kept in identical chambers. One group of 30 rats was further exposed to passive cigarette smoke for 4 weeks. No increase was observed in the levels of serum PAPP-A of both the groups: Passive smokers and not exposed to passive smoking i.e. P > 0.05. Smoking does not increase the levels of PAPP-A. (author)

  19. Involvement of extracellular matrix constituents in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lochter, Andre; Bissell, Mina J

    1995-06-01

    It has recently been established that the extracellular matrix is required for normal functional differentiation of mammary epithelia not only in culture, but also in vivo. The mechanisms by which extracellular matrix affects differentiation, as well as the nature of extracellular matrix constituents which have major impacts on mammary gland function, have only now begun to be dissected. The intricate variety of extracellular matrix-mediated events and the remarkable degree of plasticity of extracellular matrix structure and composition at virtually all times during ontogeny, make such studies difficult. Similarly, during carcinogenesis, the extracellular matrix undergoes gross alterations, the consequences of which are not yet precisely understood. Nevertheless, an increasing amount of data suggests that the extracellular matrix and extracellular matrix-receptors might participate in the control of most, if not all, of the successive stages of breast tumors, from appearance to progression and metastasis.

  20. Median-lower normal levels of serum thyroxine are associated with low triiodothyronine levels and body temperature in patients with central hypothyroidism.

    Science.gov (United States)

    Hirata, Yu; Fukuoka, Hidenori; Iguchi, Genzo; Iwahashi, Yasuyuki; Fujita, Yasunori; Hari, Yusuke; Iga, Makiko; Nakajima, Shinsuke; Nishimoto, Yuki; Mukai, Miki; Hirota, Yushi; Sakaguchi, Kazuhiko; Ogawa, Wataru; Takahashi, Yutaka

    2015-08-01

    Although it has been recommended that serum free thyroxine (FT4) levels should be targeted to middle-upper normal levels during levothyroxine (l-T4) replacement therapy in patients with central hypothyroidism (CeH), the rationale has not been clarified. A retrospective single-center study enrolled 116 patients with hypothyroidism (CeH, n=32; total thyroidectomy (Tx), n=22; primary hypothyroidism (PH), n=33; and control benign thyroid nodule (C), n=29). The patients had received L-T4 therapy at the Kobe University Hospital between 2003 and 2013. They were stratified according to serum FT4 level (≥ 1.10 or triiodothyronine (FT3) levels, FT3/FT4 ratio, and lipid profiles were compared. The effect of GH replacement therapy on thyroid function was also analyzed. FT3 levels and FT3/FT4 ratios were significantly lower in patients with CeH than in patients with PH (P<0.05) or C (P<0.05). In patients with FT4 <1.10 ng/dl, BT was significantly lower in patients with CeH (P=0.002) and Tx (P=0.005) than in patients with PH, whereas no differences were found in patients with FT4 ≥ 1.10 ng/dl. In patients with CeH, FT3 levels were higher in those with GH replacement therapy (P=0.018). In CeH, patients with median-lower normal levels of serum FT4 exhibited lower serum FT3 levels and lower BT. These results support the target levels of serum FT4 as middle-upper normal levels during l-T4 replacement therapy in patients with CeH. © 2015 European Society of Endocrinology.

  1. SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

    International Nuclear Information System (INIS)

    Zhang, Q; Lei, Y; Zheng, D; Zhu, X; Wahl, A; Lin, C; Zhou, S; Zhen, W

    2015-01-01

    Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness were created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing

  2. Cord Blood Ischemia-Modified Albumin Levels in Normal and Intrauterine Growth Restricted Pregnancies

    Directory of Open Access Journals (Sweden)

    Nicoletta Iacovidou

    2008-01-01

    Full Text Available Ischemia-modified albumin (IMA is a sensitive biomarker of cardiac ischemia. Intrauterine growth restriction (IUGR may imply fetal hypoxia, resulting in blood flow centralization in favour of vital organs (brain, heart, adrenals—‘‘brain sparing effect’’. Based on the latter, we hypothesized that cord blood IMA levels should not differ between IUGR and appropriate-for-gestational-age (AGA full-term pregnancies. IMA was measured in blood samples from doubly-clamped umbilical cords of 110 AGA and 57 asymmetric IUGR pregnancies. No significant differences in IMA levels were documented between AGA and IUGR groups. IMA levels were elevated in cases of elective cesarean section (P = .035, and offspring of multigravidas (P = .021. In conclusion, ‘‘brain sparing effect’’ is possibly responsible for the lack of differences in cord blood IMA levels at term, between IUGR and AGA groups. Furthermore, higher oxidative stress could account for the elevated IMA levels in cases of elective cesarean section, and offspring of multigravidas.

  3. ACUTE RENAL FAILURE WITH NORMAL PLASMA UREA LEVEL SECONDARY TO ACUTE PYELONEPHITIS IN A SINGLE KIDNEY PATIENT

    Directory of Open Access Journals (Sweden)

    Imperiali N

    2006-03-01

    Full Text Available SUMMARYAcute renal failure is a syndrome that usually runs with an increase in creatinine and urea plasma levels. However, there are clinical situations in which this syndrome may run with an increase in plasma creatinine keeping normal the urea one.In this report we present a case of acute renal failure with normal plasma urea level secondary to an acute pyelonephritis in a single kidney patient. The patient had an increased fractional excretion of urea which could explain the normal plasma urea levels found despite of his reduced glomerular filtration. This increased urea excretion state was interpreted as a consequence of the nephrogenic diabetes insipidus and alteration of the intra-renal urea reciclying process that the acute pyelonephritis induced. In conclusion: Acute pyelonephritis in a single kidney patient can appear as a pattern of acute renal failure with normal plasma urea levels. RESUMEN:La insuficiencia renal aguda es un sindrome que característicamente cursa con niveles plasmáticos elevados de urea y creatinina. Sin embargo, hay situaciones clínicas en las cuales este sindrome puede cursar con un incremento de la creatininemia sin presentar elevación de la uremia.En este reporte presentamos un caso clínico de una insuficiencia renal aguda con uremia normal secundaria a una pielonefritis aguda en un paciente con riñón único. El paciente presentaba una elevada excreción fraccional de urea lo cual podía explicar su uremia normal pese a estar cursando una caída del filtrado gomerular. Dicha excreción de urea elevada fue interpretada como secundaria a una diabetes insipida nefrogénica y una alteración en el recirculado intra-renal de la urea ambos producto de la pielonefritis aguda. Concluimos que la pielonefritis aguda en un paciente mono-reno puede presentarse con un patrón de insuficiencia renal aguda con uremia normal.

  4. ACUTE RENAL FAILURE WITH NORMAL PLASMA UREA LEVEL SECONDARY TO ACUTE PYELONEPHITIS IN A SINGLE KIDNEY PATIENT

    Directory of Open Access Journals (Sweden)

    Algranati L

    2007-04-01

    Full Text Available SUMMARY: Acute renal failure is a syndrome that usually runs with an increase in creatinine and urea plasma levels. However, there are clinical situations in which this syndrome may run with an increase in plasma creatinine keeping normal the urea one. In this report we present a case of acute renal failure with normal plasma urea level secondary to an acute pyelonephritis in a single kidney patient. The patient had an increased fractional excretion of urea which could explain the normal plasma urea levels found despite of his reduced glomerular filtration. This increased urea excretion state was interpreted as a consequence of the nephrogenic diabetes insipidus and alteration of the intra-renal urea reciclying process that the acute pyelonephritis induced. In conclusion: Acute pyelonephritis in a single kidney patient can appear as a pattern of acute renal failure with normal plasma urea levels.RESUMEN: La insuficiencia renal aguda es un sindrome que característicamente cursa con niveles plasmáticos elevados de urea y creatinina. Sin embargo, hay situaciones clínicas en las cuales este sindrome puede cursar con un incremento de la creatininemia sin presentar elevación de la uremia. En este reporte presentamos un caso clínico de una insuficiencia renal aguda con uremia normal secundaria a una pielonefritis aguda en un paciente con riñón único. El paciente presentaba una elevada excreción fraccional de urea lo cual podía explicar su uremia normal pese a estar cursando una caída del filtrado gomerular. Dicha excreción de urea elevada fue interpretada como secundaria a una diabetes insipida nefrogénica y una alteración en el recirculado intra-renal de la urea ambos producto de la pielonefritis aguda. Concluimos que la pielonefritis aguda en un paciente mono-reno puede presentarse con un patrón de insuficiencia renal aguda con uremia normal.

  5. Association of Irisin Plasma Levels with Anthropometric Parameters in Children with Underweight, Normal Weight, Overweight, and Obesity

    Directory of Open Access Journals (Sweden)

    Leticia Elizondo-Montemayor

    2017-01-01

    Full Text Available The correlations between irisin levels, physical activity, and anthropometric measurements have been extensively described in adults with considerable controversy, but little evidence about these relationships has been found in children. The objective of this study is to correlate the plasma levels of irisin in underweight, normal weight, overweight, and obese children with anthropometric parameters and physical activity levels. A cross-sample of 40 children was divided into the following groups on the basis of body mass index (BMI percentile. The correlations of plasma irisin levels with physical activity, anthropometric, and metabolic measurements were determined. Plasma irisin levels (ng/mL were lower for the underweight group (164.2 ± 5.95 than for the normal weight and obese groups (182.8 ± 5.58; p<0.05. Irisin levels correlated positively with BMI percentile (0.387, waist circumference (0.373, and fat-free mass (0.353; p<0.05, but not with body muscle mass (−0.027. After a multiple linear regression analysis, only BMI percentile (0.564; p<0.008 showed a positive correlation with irisin. Our results indicated no association with metabolic parameters. A negative correlation with physical activity was observed. Interrelationships among body components might influence irisin levels in children.

  6. Mandibulary dental arch form differences between level four polynomial method and pentamorphic pattern for normal occlusion sample

    Directory of Open Access Journals (Sweden)

    Y. Yuliana

    2011-07-01

    Full Text Available The aim of an orthodontic treatment is to achieve aesthetic, dental health and the surrounding tissues, occlusal functional relationship, and stability. The success of an orthodontic treatment is influenced by many factors, such as diagnosis and treatment plan. In order to do a diagnosis and a treatment plan, medical record, clinical examination, radiographic examination, extra oral and intra oral photos, as well as study model analysis are needed. The purpose of this study was to evaluate the differences in dental arch form between level four polynomial and pentamorphic arch form and to determine which one is best suitable for normal occlusion sample. This analytic comparative study was conducted at Faculty of Dentistry Universitas Padjadjaran on 13 models by comparing the dental arch form using the level four polynomial method based on mathematical calculations, the pattern of the pentamorphic arch and mandibular normal occlusion as a control. The results obtained were tested using statistical analysis T student test. The results indicate a significant difference both in the form of level four polynomial method and pentamorphic arch form when compared with mandibular normal occlusion dental arch form. Level four polynomial fits better, compare to pentamorphic arch form.

  7. High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men.

    Directory of Open Access Journals (Sweden)

    Jieun Lee

    Full Text Available We performed a follow-up study to address whether high sensitivity C-reactive protein (hs-CRP levels within the normal range can predict the development of non-alcoholic fatty liver disease (NAFLD in healthy male subjects. Among15347 male workers between 30 and 59 years old who received annual health check-ups in 2002, a NAFLD-free cohort of 4,138 was followed through December 2009. Alcohol consumption was assessed with a questionnaire. At each visit, abdominal ultrasonography was performed to identify fatty liver disease. The COX proportional hazard model was used to evaluate the relationship between hs-CRP and incident NAFLD. During the follow-up period, 28.8% (1191 of 4138 of participants developed NAFLD. The hazard ratios of NAFLD were increased by hs-CRP categories within the normal range in the non-adjusted model and age-adjusted model. After adjusting for age, exercise, smoking, BMI, systolic BP, triglyceride, and fasting glucose, these incidences were only increased between the lowest and the highest hs-CRP categories. The risk for NAFLD increased as the hs-CRP level increased (p< 0.001. As the hs-CRP level increased within the healthy cohort, the risk of developing NAFLD increased. This trend remained true even if the hs-CRP level remained within the normal range. hs-CRP can be used as a predictor of NAFLD, as well as other obesity-associated diseases. Therefore, individuals with higher hs-CRP levels (even within the normal range may require appropriate follow-up and management to prevent NAFLD development.

  8. Impact of Different Normality Thresholds for 24-hour ABPM at the Primary Health Care Level

    Directory of Open Access Journals (Sweden)

    Guilherme Brasil Grezzana

    Full Text Available Abstract Background: Hypertension is an important risk factor for cardiovascular outcomes. Primary health care (PHC physicians should be prepared to act appropriately in the prevention of cardiovascular risk factors. However, the rates of patients with control of blood pressure (BP remain low. The impact of the reclassification of high BP by 24-hour ambulatory BP monitoring (ABPM can lead to different medical decisions in PHC. Objective: To evaluate the agreement between the BP measured by a conventional method by PHC physicians and by 24-hour ABPM, considering different BP normal thresholds for the 24-hour ABPM according to the V Brazilian ABPM Guidelines and the European Society of Hypertension Guidelines. Methods: A cross-sectional study including 569 hypertensive patients. The BP was initially measured by the PHC physicians and, later, by 24-hour ABPM. The BP measurements were obtained independently between the two methods. The therapeutic targets for the conventional BP followed the guidelines by the Eighth Joint National Committee (JNC 8, the V ABPM Brazilian Guidelines, and the 2013 European Hypertension Guidelines. Results: There was an accuracy of 54.8% (95% confidence interval [95%CI] 0.51 - 0.58% for the BP measured with the conventional method when compared with the 24-hour ABPM, with a sensitivity of 85% (95%CI 80.8 - 88.6%, specificity of 31.9% (95%CI 28.7 - 34.7%, and kappa value of 0.155, when considering the European Hypertension Guidelines. When using more stringent thresholds to characterize the BP as "normal" by ABPM, the accuracy was 45% (95%CI 0.41 - 0.47% for conventional measurement when compared with 24-hour ABPM, with a sensitivity of 86.7% (95%CI 0.81 - 0.91%, specificity of 29% (95%CI 0.26 - 0.30%, and kappa value of 0.103. Conclusion: The BP measurements obtained by PHC physicians showed low accuracy when compared with those obtained by 24-hour ABPM, regardless of the threshold set by the different guidelines.

  9. Association between serum 25-hydroxyvitamin D levels and bone mineral density in normal postmenopausal women

    Directory of Open Access Journals (Sweden)

    Vasundhara Kamineni

    2016-01-01

    Full Text Available Aim: This study was conducted with the objective of assessing serum 25-hydroxyvitamin D (25(OHD in postmenopausal women (PMW, to detect osteopenia or osteoporosis in PMW and to establish a correlation between serum 25(OHD levels and bone mineral density (BMD. Materials and Methods: A total of 100 healthy PMW were selected, and a prospective observational study was conducted to correlate the BMD with serum 25(OHD levels. Their laboratory investigations along with serum 25(OHD levels were done. Their BMD was assessed with dual-energy X-ray absorptiometry at lumbar spine and neck of femur; T-scores were derived. Correlation analysis was done to investigate the relationship between serum 25(OHD levels and BMD. Results: The proportion of osteoporosis at the hip was 31.9% in deficient group, 16.1% in insufficient, and 18.2% in sufficient group and at lumbar spine, it was 27.7%, 16.1%, and 22.7%, respectively. Forty-seven percent of PMW had deficient (<20 ng/ml serum 25(OHD levels and 31% had insufficiency. T-score at hip in deficient group was −2.05 ± 0.25, and in an insufficient group, it was −1.79 ± 0.13; T-score at lumbar spine was −1.92 ± 0.12 and −1.79 ± 0.12, respectively, but both were not statistically significant. Osteoporosis was seen in 24%, osteopenia in 55% at hip level and 23% and 59% respectively at lumbar spine. There was no association between serum 25(OHD levels and BMD neither at hip nor at lumbar spine ( P = 0.51 and P = 0.79 respectively. Conclusion: In this study, among our cohort of patients there was no correlation between serum 25(OHD levels and BMD. However, Vitamin D deficiency coexists with low BMD. Vitamin D insufficiency is a common risk factor for osteoporosis associated with increased bone remodeling and low bone mass.

  10. Exercise training normalizes skeletal muscle vascular endothelial growth factor levels in patients with essential hypertension

    DEFF Research Database (Denmark)

    Hansen, Ane Håkansson; Nielsen, Jens Jung; Saltin, Bengt

    2010-01-01

    METHODS: Vascular endothelial growth factor (VEGF) protein and capillarization were determined in muscle vastus lateralis biopsy samples in individuals with essential hypertension (n = 10) and normotensive controls (n = 10). The hypertensive individuals performed exercise training for 16 weeks....... Muscle samples as well as muscle microdialysis fluid samples were obtained at rest, during and after an acute exercise bout, performed prior to and after the training period, for the determination of muscle VEGF levels, VEGF release, endothelial cell proliferative effect and capillarization. RESULTS......: Prior to training, the hypertensive individuals had 36% lower levels of VEGF protein and 22% lower capillary density in the muscle compared to controls. Training in the hypertensive group reduced (P

  11. Serum IGF1 and insulin levels in girls with normal and precocious puberty

    DEFF Research Database (Denmark)

    Sørensen, Kaspar; Aksglaede, Lise; Petersen, Jørgen Holm

    2012-01-01

    IGF1 plays an important role in growth and metabolism during puberty. IGF1 levels are increased in girls with central precocious puberty (CPP). However, the relationship with insulin before and during gonadal suppression is unknown. In addition, the influence of the exon 3-deleted GH receptor gene...

  12. Diurnal rhythm in serum levels of inhibin B in normal men

    DEFF Research Database (Denmark)

    Carlsen, E; Olsson, C; Petersen, J H

    1999-01-01

    in the early morning hours and lower values in the late afternoon and evening. We did not find evidence for a role of FSH in this diurnal variation of inhibin B. However, covariation with serum levels of testosterone and estradiol suggested that these hormones might play a role in the diurnal rhythm of inhibin...

  13. Effect of glibenclamide on insulin release at moderate and high blood glucose levels in normal man

    NARCIS (Netherlands)

    Ligtenberg, JJM; Venker, CE; Sluiter, WJ; VanHaeften, TW

    Insulin release occurs in two phases; sulphonylurea derivatives may have different potencies in stimulating first-and second-phase insulin release. We studied the effect of glibenclamide on insulin secretion at submaximally and maximally stimulating blood glucose levels with a primed hyperglycaemic

  14. Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

    Science.gov (United States)

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2015-01-01

    Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages.

  15. Insulin and leptin levels in overweight and normal-weight Iranian adolescents: The CASPIAN-III study

    Directory of Open Access Journals (Sweden)

    Ehsan Bahrami

    2014-01-01

    Full Text Available Background: In this study, we aim to compare insulin and leptin levels in adolescents with or without excess weight and in those with or without abdominal obesity. Materials and Methods : This case-control study was conducted among 486 samples. We randomly selected 243 overweight and an equal number of normal-weight adolescents from among participants of the third survey of a national surveillance program entitled "Childhood and Adolescence Surveillance and PreventIon of Adult Non-communicable diseases study." Serum insulin and leptin were compared between two groups and their correlation was determined with other variables. Results: The mean age and body mass index (BMI of participants were 14.10 ± 2.82 years and 22.12 ± 6.49 kg/m 2 , respectively. Leptin and insulin levels were higher in overweight than in normal-weight adolescents (P < 0.05. Leptin level was higher in children with abdominal obesity than in their other counterparts (P < 0.001. Leptin level was correlated with age, fasting blood glucose, BMI, and insulin level. Conclusion: Insulin and leptin levels were higher among overweight and obese children, which may reflect insulin and leptin-resistance. Given the complications of excess weight from early life, prevention and controlling childhood obesity should be considered as a health priority.

  16. Aspirin effects on lymphocyte cyclic AMP levels in normal human subjects.

    Science.gov (United States)

    Snider, D E; Parker, C W

    1976-01-01

    In purified lymphocytes from the peripheral blood of healthy human subjects who had ingested therapeutic doses of aspirin, there was a significant decrease in resting cyclic AMP levels as well as a partial inhibition of the rise in cyclic AMP with isoproterenol or prostaglandin E1. These changes were seen as early as 30 min after aspirin ingestion and did not appear to result from aspirin effects on lymphocyte recovery, purity, viability, or relative number of thymus- or bone marrow-derived lymphocytes. In contrast, the direct addition of aspirin to suspensions of purified peripheral lymphocytes did not significantly alter their cyclic AMP levels. However, an effect of aspirin could be obtained in vitro if aspirin was added to unprocessed whole blood during the dextran sedimentation phase of the cell purification. Thus the effect of aspirin on lymphocyte cyclic AMP metabolism, may be indirect, through other cells present in the peripheral blood. PMID:182720

  17. EEG responses to low-level chemicals in normals and cacosmics.

    Science.gov (United States)

    Schwartz, G E; Bell, I R; Dikman, Z V; Fernandez, M; Kline, J P; Peterson, J M; Wright, K P

    1994-01-01

    Recent studies from the University of Arizona indicate that normal subjects, both college students and the elderly, can register the presence of low-intensity odors in the electroencephalogram (EEG) in the absence of conscious awareness of the odors. The experimental paradigm involves subjects sniffing pairs of bottles, one containing an odorant (e.g. isoamyl acetate) dissolved in an odorless solvent (water or liquid silicone), the other containing just the solvent, while 19 channels of EEG are continuously recorded. For the low-intensity odor conditions, concentrations are adjusted downward (decreased) until subjects correctly identify the odor bottle at chance (50%). The order of odorants, concentrations, and hand holding the control bottle, are counterbalanced within and across subjects. Three previous experiments found that alpha activity (8-12 hz) decreased in midline and posterior regions when subjects sniffed the low-intensity odors. The most recent study suggests that decreased theta activity (4-8 hz) may reflect sensory registration and decreased alpha activity may reflect perceptual registration. In a just completed experiment involving college students who were selected based on combinations of high and low scores on a scale measuring cacosmia (chemical odor intolerance) and high and low scores on a scale measuring depression, cacosmic subjects (independent of depression) showed greater decreases in low-frequency alpha (8-10 hz) and greater increases in low-frequency beta (12-16 hz) to the solvent propylene glycol compared to an empty bottle. Topographic EEG mapping to low-intensity odorants may provide a useful tool for investigating possible increased sensitivity to specific chemicals in chemically sensitive individuals.

  18. Impact of Different Normality Thresholds for 24-hour ABPM at the Primary Health Care Level.

    Science.gov (United States)

    Grezzana, Guilherme Brasil; Moraes, David William; Stein, Airton Tetelbon; Pellanda, Lucia Campos

    2017-02-01

    Hypertension is an important risk factor for cardiovascular outcomes. Primary health care (PHC) physicians should be prepared to act appropriately in the prevention of cardiovascular risk factors. However, the rates of patients with control of blood pressure (BP) remain low. The impact of the reclassification of high BP by 24-hour ambulatory BP monitoring (ABPM) can lead to different medical decisions in PHC. To evaluate the agreement between the BP measured by a conventional method by PHC physicians and by 24-hour ABPM, considering different BP normal thresholds for the 24-hour ABPM according to the V Brazilian ABPM Guidelines and the European Society of Hypertension Guidelines. A cross-sectional study including 569 hypertensive patients. The BP was initially measured by the PHC physicians and, later, by 24-hour ABPM. The BP measurements were obtained independently between the two methods. The therapeutic targets for the conventional BP followed the guidelines by the Eighth Joint National Committee (JNC 8), the V ABPM Brazilian Guidelines, and the 2013 European Hypertension Guidelines. There was an accuracy of 54.8% (95% confidence interval [95%CI] 0.51 - 0.58%) for the BP measured with the conventional method when compared with the 24-hour ABPM, with a sensitivity of 85% (95%CI 80.8 - 88.6%), specificity of 31.9% (95%CI 28.7 - 34.7%), and kappa value of 0.155, when considering the European Hypertension Guidelines. When using more stringent thresholds to characterize the BP as "normal" by ABPM, the accuracy was 45% (95%CI 0.41 - 0.47%) for conventional measurement when compared with 24-hour ABPM, with a sensitivity of 86.7% (95%CI 0.81 - 0.91%), specificity of 29% (95%CI 0.26 - 0.30%), and kappa value of 0.103. The BP measurements obtained by PHC physicians showed low accuracy when compared with those obtained by 24-hour ABPM, regardless of the threshold set by the different guidelines. A hipertensão arterial sistêmica é um fator de risco importante para

  19. Effect of low to normal dietary phosphorus levels on zinc metabolism and tissue distribution in calves

    International Nuclear Information System (INIS)

    Laflamme, D.P.; Miller, W.J.; Neathery, M.W.; Gentry, R.P.; Blackmon, D.M.; Logner, K.R.; Fielding, A.S.

    1985-01-01

    Sixteen 10-wk-old, phosphorus (P)-depleted Holstein bull calves were fed for 6 wk a control diet containing .08% P or P-supplemented diets containing .14, .20 or .32% P with supplemental P from two sources (CDP and Dynafos). The diets contained .45, .56, .66 and .87% Ca. After 5 wk of the experiment, the calves were dosed orally with 65 Zn, and daily total fecal collections were initiated. At the end of the experimental period, the calves were killed and tissue samples were taken for total Zn and 65 Zn analyses. Growth, feed intake and feed efficiency improved with increasing dietary P levels. Level of dietary P and Ca had little or no effect on total Zn content of rib, tibia, liver, heart, kidney, muscle or blood. Likewise, 65 Zn absorption and content in most tissues were not affected. The results do not preclude the possibility of some minor effects of P levels on Zn metabolism. However, it is apparent that when adequate Zn is fed, any effects are likely to be of little or no practical importance

  20. Tinnitus is associated with reduced sound level tolerance in adolescents with normal audiograms and otoacoustic emissions

    Science.gov (United States)

    Sanchez, Tanit Ganz; Moraes, Fernanda; Casseb, Juliana; Cota, Jaci; Freire, Katya; Roberts, Larry E.

    2016-01-01

    Recent neuroscience research suggests that tinnitus may reflect synaptic loss in the cochlea that does not express in the audiogram but leads to neural changes in auditory pathways that reduce sound level tolerance (SLT). Adolescents (N = 170) completed a questionnaire addressing their prior experience with tinnitus, potentially risky listening habits, and sensitivity to ordinary sounds, followed by psychoacoustic measurements in a sound booth. Among all adolescents 54.7% reported by questionnaire that they had previously experienced tinnitus, while 28.8% heard tinnitus in the booth. Psychoacoustic properties of tinnitus measured in the sound booth corresponded with those of chronic adult tinnitus sufferers. Neither hearing thresholds (≤15 dB HL to 16 kHz) nor otoacoustic emissions discriminated between adolescents reporting or not reporting tinnitus in the sound booth, but loudness discomfort levels (a psychoacoustic measure of SLT) did so, averaging 11.3 dB lower in adolescents experiencing tinnitus in the acoustic chamber. Although risky listening habits were near universal, the teenagers experiencing tinnitus and reduced SLT tended to be more protective of their hearing. Tinnitus and reduced SLT could be early indications of a vulnerability to hidden synaptic injury that is prevalent among adolescents and expressed following exposure to high level environmental sounds. PMID:27265722

  1. Comparison of Different Levels of Reading Comprehension between Hearing-Impaired Loss and Normal-Hearing Students

    Directory of Open Access Journals (Sweden)

    Azam Sharifi

    2011-12-01

    Full Text Available Background and Aim: Reading skill is one of the most important necessities of students' learning in everyday life. This skill is referred to the ability of comprehension, comment and conclusion from texts and receiving the meaning of the massage which is composed. Educational development in any student has a direct relation with the ability of the comprehension. This study is designed to investigate the effects of hearing loss on reading comprehension in hearing-impaired students compared to normal-hearing ones.Methods: Seventeen hearing-impaired students in 4th year of primary exceptional schools in Karaj, Robatkarim and Shahriyar, Iran, were enrolled in this cross-sectional study. Seventeen normal-hearing students were randomly selected from ordinary schools next to exceptional ones as control group. They were compared for different levels of reading comprehension using the international standard booklet (PIRLS 2001. Results: There was a significant difference in performance between hearing-impaired and normal- hearing students in different levels of reading comprehension (p<0.05.Conclusion: Hearing loss has negative effects on different levels of reading comprehension, so in exceptional centers, reconsideration in educational planning in order to direct education from memorizing to comprehension and deeper layers of learning seems necessary.

  2. Effect of aluminum chloride on blood glucose level and lipid profile in normal, diabetic and treated diabetic rats.

    Science.gov (United States)

    Konda, Venugopala Rao; Eerike, Madhavi; Chary, R Prasanth; Arunachalam, Ruckmani; Yeddula, Venkata Ramana; Meti, Vinayak; Devi, T Sobita

    2017-01-01

    The objectives of the study were to assess evaluate the effects of aluminum chloride (AlCl 3 ) on blood glucose and lipid levels in normal, diabetic, and glibenclamide-treated diabetic rats. Forty-two male Wistar rats were divided into seven groups of six each. Group I was normal control, Groups II and III were given AlCl 3 50 and 100 mg/kg, and Group IV to VII were administered with streptozotocin (STZ) (60 mg/kg) intraperitoneally. Group IV was diabetic control, Group V in addition was given AlCl 3 50 mg/kg, Group VI glibenclamide (10 mg/kg), and Group VII glibenclamide and AlCl 3 (50 mg/kg) per-oral daily for 28 days. Blood glucose and lipid levels were estimated at base line, after diabetes was set in and on the last day of study. Histopathological changes in pancreas, liver, and kidney were studied. No significant change was observed in blood glucose and lipid levels in Group I. Group II and III showed a dose-dependent significant increase in blood glucose was observed. Group V had a reduction in blood glucose but not to the nondiabetic level. Group VI had significant reduction in blood sugar. In Group VII, treated with glibenclamide and AlCl 3 , there was no significant change in blood glucose reduction compared to Group VI. Lipid levels were reduced in groups treated with AlCl 3 and glibenclamide and not in other groups. Gross tissue damage was seen in pancreas in STZ group and in liver and kidney in AlCl 3 groups. AlCl 3 administration in Wistar rats caused in significant hyperglycemia in normal rats, hypoglycemia in diabetic rats, and did not influenced hypoglycemic effect of glibenclamide and in addition, resulted in reduction in lipid levels.

  3. Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia.

    Directory of Open Access Journals (Sweden)

    Adriana Cristofano

    Full Text Available This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer's disease. Twenty-nine patients with probable Alzheimer's disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L to subjective memory complaint (4.3±0.9 μmol/L, mild cognitive impairment (4.0±0.53 μmol/L, up to Alzheimer's disease (3.5±0.6 μmol/L group (p<0.001. The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer's disease group; and subjective memory complaint vs. Alzheimer's disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer's disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer's disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer's disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal

  4. Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia

    Science.gov (United States)

    Sapere, Nadia; La Marca, Giancarlo; Angiolillo, Antonella; Vitale, Michela; Corbi, Graziamaria; Scapagnini, Giovanni; Intrieri, Mariano; Russo, Claudio

    2016-01-01

    This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer’s disease. Twenty-nine patients with probable Alzheimer’s disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L) to subjective memory complaint (4.3±0.9 μmol/L), mild cognitive impairment (4.0±0.53 μmol/L), up to Alzheimer’s disease (3.5±0.6 μmol/L) group (p<0.001). The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer’s disease group; and subjective memory complaint vs. Alzheimer’s disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer’s disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer’s disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer’s disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal

  5. High Mutation Levels are Compatible with Normal Embryonic Development in Mlh1-Deficient Mice.

    Science.gov (United States)

    Fan, Xiaoyan; Li, Yan; Zhang, Yulong; Sang, Meixiang; Cai, Jianhui; Li, Qiaoxia; Ozaki, Toshinori; Ono, Tetsuya; He, Dongwei

    2016-10-01

    To elucidate the role of the mismatch repair gene Mlh1 in genome instability during the fetal stage, spontaneous mutations were studied in Mlh1-deficient lacZ-transgenic mouse fetuses. Mutation levels were high at 9.5 days post coitum (dpc) and gradually increased during the embryonic stage, after which they remained unchanged. In addition, mutations that were found in brain, liver, spleen, small intestine and thymus showed similar levels and no statistically significant difference was found. The molecular nature of mutations at 12.5 dpc in fetuses of Mlh1 +/+ and Mlh1 -/- mice showed their own unique spectra, suggesting that deletion mutations were the main causes in the deficiency of the Mlh1 gene. Of note, fetuses of irradiated mice exhibited marked differences such as post-implantation loss and Mendelian distribution. Collectively, these results strongly suggest that high mutation ofMlh1 -/- -deficient fetuses has little effect on the fetuses during their early developmental stages, whereas Mlh1 -/- -deficient fetuses from X-ray irradiated mothers are clearly effected.

  6. Major congenital malformations in the high and normal level radiation areas of southwest coast of Kerala

    International Nuclear Information System (INIS)

    Sudheer, K.R.; Jaikrishan, G.; Andrews, V.J.; Koya, P.K.M.; Seshadri, M.; Jagadeesan, C.K.; Madhusoodhanan, M.

    2012-01-01

    Congenital malformations are defects in organogenesis during the fetal periods and its influence on the individual may vary according to the type of malformation. Some congenital malformations are trivial and may not have any significance but for a minimal cosmetic deformity. Major malformations on the contrary may be severe enough to be life-threatening with serious structural, functional or cosmetic disability requiring surgical or medical management and are an important cause of mortality and morbidity all over the world. The present paper analyses the major malformations detected during the monitoring of newborns in selected government hospitals in and around the high level natural radiation areas of Kerala, a narrow strip of land in the southwest coast extending from Purakkad panchayat of Alapuzha district in the north to Neendakara Panchayat of Quilon district in the south. The coastal area has natural deposits of Monazite sand containing Thorium. Thorium together with its daughter products accounts for the elevated levels of natural radiation. The finding in general was in conformity with similar works on malformations

  7. Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers.

    Science.gov (United States)

    Jung, Caroline; Greco, Santo; Nguyen, Hanh H T; Ho, Jui T; Lewis, John G; Torpy, David J; Inder, Warrick J

    2014-11-26

    Glucocorticoid replacement is essential in patients with primary and secondary adrenal insufficiency, but many patients remain on higher than recommended dose regimens. There is no uniformly accepted method to monitor the dose in individual patients. We have compared cortisol concentrations in plasma, saliva and urine achieved following "physiological" and "stress" doses of hydrocortisone as potential methods for monitoring glucocorticoid replacement. Cortisol profiles were measured in plasma, saliva and urine following "physiological" (20 mg oral) or "stress" (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to endogenous cortisol levels (12 subjects). Total plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5 h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5 h, and hourly from time 0 to 5 h following administration of oral or intravenous hydrocortisone. Plasma free cortisol was calculated using Coolens' equation. Plasma, salivary and urine cortisol at 2 h after oral hydrocortisone gave a good indication of peak cortisol concentrations, which were uniformly supraphysiological. Intravenous hydrocortisone administration achieved very high 30 minute cortisol concentrations. Total plasma cortisol correlated significantly with both saliva and urine cortisol after oral and intravenous hydrocortisone (P cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in hypoadrenal patients.

  8. Association of Tumor Growth Factor-β and Interferon-γ Serum Levels With Insulin Resistance in Normal Pregnancy.

    Science.gov (United States)

    Sotoodeh Jahromi, Abdolreza; Sanie, Mohammad Sadegh; Yusefi, Alireza; Zabetian, Hassan; Zareian, Parvin; Hakimelahi, Hossein; Madani, Abdolhossien; Hojjat-Farsangi, Mohammad

    2015-09-28

    Pregnancy is related to change in glucose metabolism and insulin production. The aim of our study was to determine the association of serum IFN-γ and TGF- β levels with insulin resistance during normal pregnancy. This cross sectional study was carried out on 97 healthy pregnant (in different trimesters) and 28 healthy non-pregnant women. Serum TGF-β and IFN- γ level were measured by ELISA method. Pregnant women had high level TGF-β and low level IFN-γ as compared non-pregnant women. Maternal serum TGF-β concentration significantly increased in third trimester as compared first and second trimester of pregnancy. Maternal serum IFN-γ concentration significantly decreased in third trimester as compared first and second trimester of pregnancy. Pregnant women exhibited higher score of HOMA IR as compared non-pregnant women. There were association between gestational age with body mass index (r=0.28, P=0.005), TGF-β (r=0.45, PInsulin resistance and TGF-β (r=0.17, p=0.05). Our findings suggest that changes in maternal cytokine level in healthy pregnant women were anti-inflammatory. Furthermore, Tumor Growth Factor-β appears has a role in induction insulin resistance in healthy pregnant women. However, further studies needed to evaluate role of different cytokines on insulin resistance in normal pregnancy.

  9. A comparison study of lipid profile levels between skin tags affected people and normal population in Tehran, Iran

    Directory of Open Access Journals (Sweden)

    Abbas Rasi

    2014-01-01

    Full Text Available Background: For many years the association of skin tags and endocrynopathies has been postulated, although many reports are available but it has never been evaluated to mean normal population. Dyslipidemia is a frequent disorder among people and seemed to be necessary for screening within skin tag condition. This study is designed to find any possible association between skin tags and dyslipidemia. Materials and Methods: From April 2009 to June 2011, 168 patients enrolled the study. Among the remaining 152 patients, there were 89 females (58.5% and 63 males (%41.5. Based on the TLGS study 136 men and 220 women enrolled the control group of study. The mean age was 28.4 years. Patients trained to have normal free diet for at least 1 month then referred to the laboratory. Blood samples were taken over 12 hours fasting with 2 hours intervals. Hypertriglyceridemia was defined as plasma level ≥160 mg/dl for men and ≥130 mg/dl for women. Hypercholesterolemia pointed at its value >200 mg/dl. Normal HDL levels was defined as >39 mg/dl for men and >35 mg/dl to women. Results: Mean skin tag number was 12.6 per subject. The most frequent localizations of skin tags were neck and upper chest (mean number: 13.4, 48.9% followed by axilla (mean number: 11.6, 33% and breast (10.2, 10.1% in the patient group. The mean cholesterol level of case group was 192.2 ± 33.1 mg/dl, while it was 187.0 ± 42 mg/dl in the control group. The mean ± SD for triglyceride was 132.1 ± 69 mg/dl in comparison to 129 ± 74 in the control group. Conclusion: The study showed no significant differences between normal population and patients′ lipid profile.

  10. Maternal blood total oxypurines and erythrocyte 2,3-diphosphoglycerate levels during normal pregnancy.

    Science.gov (United States)

    Mizutani, S; Akiyama, H; Kurauchi, O; Taira, H; Yamada, R; Narita, O; Tomoda, Y

    1985-01-01

    The effects of pregnancy on the levels of maternal plasma total oxypurines (hypoxanthine, xanthine and uric acid) and erythrocyte 2,3-diphosphoglycerate (2,3-DPG) was investigated. With advancing gestation there was a slight increasing tendency in plasma total oxypurines as well as erythrocyte 2,3-DPG in pregnant women. When the ratio of 2,3-DPG to total oxypurines was calculated, the ratio was almost unchanged until week 34. After week 35, the ratio decreased to week 37; the ratios between week 37 and 40 had similar values to cord blood. The above data suggest that the changes of these metabolites in maternal peripheral blood may be indicative for hypoxia with fetoplacental tissue.

  11. Return to normal streamflows and water levels: summary of hydrologic conditions in Georgia, 2013

    Science.gov (United States)

    Knaak, Andrew E.; Caslow, Kerry; Peck, Michael F.

    2015-01-01

    The U.S. Geological Survey (USGS) South Atlantic Water Science Center (SAWSC) Georgia office, in cooperation with local, State, and other Federal agencies, maintains a long-term hydrologic monitoring network of more than 340 real-time continuous-record streamflow-gaging stations (streamgages), including 10 real-time lake-level monitoring stations, 67 real-time surface-water-quality monitors, and several water-quality sampling programs. Additionally, the SAWSC Georgia office operates more than 180 groundwater monitoring wells, 39 of which are real-time. The wide-ranging coverage of streamflow, reservoir, and groundwater monitoring sites allows for a comprehensive view of hydrologic conditions across the State. One of the many benefits of this monitoring network is that the analyses of the data provide a spatially distributed overview of the hydrologic conditions of creeks, rivers, reservoirs, and aquifers in Georgia.

  12. Magnesium sulfate reduces formalin-induced orofacial pain in rats with normal magnesium serum levels.

    Science.gov (United States)

    Srebro, Dragana P; Vučković, Sonja M; Dožić, Ivan S; Dožić, Branko S; Savić Vujović, Katarina R; Milovanović, Aleksandar P; Karadžić, Branislav V; Prostran, Milica Š

    2018-02-01

    In humans, orofacial pain has a high prevalence and is often difficult to treat. Magnesium is an essential element in biological a system which controls the activity of many ion channels, neurotransmitters and enzymes. Magnesium produces an antinociceptive effect in neuropathic pain, while in inflammatory pain results are not consistent. We examined the effects of magnesium sulfate using the rat orofacial formalin test, a model of trigeminal pain. Male Wistar rats were injected with 1.5% formalin into the perinasal area, and the total time spent in pain-related behavior (face rubbing) was quantified. We also spectrophotometrically determined the concentration of magnesium and creatine kinase activity in blood serum. Magnesium sulfate administered subcutaneously (0.005-45mg/kg) produced significant antinociception in the second phase of the orofacial formalin test in rats at physiological serum concentration of magnesium. The effect was not dose-dependent. The maximum antinociceptive effect of magnesium sulfate was about 50% and was achieved at doses of 15 and 45mg/kg. Magnesium did not affect increase the levels of serum creatine kinase activity. Preemptive systemic administration of magnesium sulfate as the only drug can be used to prevent inflammatory pain in the orofacial region. Its analgesic effect is not associated with magnesium deficiency. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  13. The levels of adipokines in relation to hormonal changes during the menstrual cycle in young, normal-weight women

    Directory of Open Access Journals (Sweden)

    Katarzyna Wyskida

    2017-11-01

    Full Text Available Context: The aim of this study was to assess the plasma leptin, adiponectin, resistin, visfatin/NAMPT, omentin-1, vaspin, apelin, TNF-α, IL-6 and RBP4 levels in relation to hormonal changes during the menstrual cycle in young, healthy, normal-weight women. Methods: The study involved 52 young, healthy, normal-weight women. Anthropometric parameters, body composition and levels of plasma leptin, adiponectin, resistin, visfatin/NAMPT, omentin-1, vaspin, apelin, TNF-α, IL-6 and RBP4 in addition to serum FSH, LH, estradiol, progesterone, 17-OH progesterone, androgens, SHBG and insulin concentrations were measured during a morning in fasting state three times: between days 2–4, days 12–14 and days 24–26 of the menstrual cycle. Results: Plasma adiponectin, omentin-1, resistin and visfatin/NAMPT, apelin, TNF-α, IL-6 and RBP4 concentrations were stable during the menstrual cycle, while leptin and vaspin levels were significantly higher in both the midcycle and the luteal phases than those in the follicular phase. Multivariate regression analyses revealed that changes in leptin and vaspin levels between the follicular and the luteal phase are strongly related to changes in total testosterone levels. Conclusions: Our results revealed stable levels of adipokines during the phases of the physiological menstrual cycle, except for leptin and vaspin, which showed increased levels in both the midcycle and the luteal phases. This effect was significantly associated with changes in the secretion of testosterone, 17-OH progesterone and insulin in the luteal phase.

  14. Exposure to meat-derived carcinogens and bulky DNA adduct levels in normal-appearing colon mucosa.

    Science.gov (United States)

    Ho, Vikki; Brunetti, Vanessa; Peacock, Sarah; Massey, Thomas E; Godschalk, Roger W L; van Schooten, Frederik J; Ashbury, Janet E; Vanner, Stephen J; King, Will D

    2017-09-01

    Meat consumption is a risk factor for colorectal cancer. This research investigated the relationship between meat-derived carcinogen exposure and bulky DNA adduct levels, a biomarker of DNA damage, in colon mucosa. Least squares regression was used to examine the relationship between meat-derived carcinogen exposure (PhIP and meat mutagenicity) and bulky DNA adduct levels in normal-appearing colon tissue measured using 32 P-postlabelling among 202 patients undergoing a screening colonoscopy. Gene-diet interactions between carcinogen exposure and genetic factors relevant to biotransformation and DNA repair were also examined. Genotyping was conducting using the MassARRAY ® iPLEX ® Gold SNP Genotyping assay. PhIP and higher meat mutagenicity exposures were not associated with levels of bulky DNA adducts in colon mucosa. The XPC polymorphism (rs2228001) was found to associate with bulky DNA adduct levels, whereby genotypes conferring lower DNA repair activity were associated with higher DNA adduct levels than the normal activity genotype. Among individuals with genotypes associated with lower DNA repair (XPD, rs13181 and rs1799179) or detoxification activity (GSTP1, rs1695), higher PhIP or meat mutagenicity exposures were associated with higher DNA adduct levels. Significant interactions between the XPC polymorphism (rs2228000) and both dietary PhIP and meat mutagenicity on DNA adduct levels was observed, but associations were inconsistent with the a priori hypothesized direction of effect. Exposure to meat-derived carcinogens may be associated with increased DNA damage occurring directly in the colon among genetically susceptible individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Mortensen, Stefan Peter; Hellsten, Ylva

    2013-01-01

    performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. CONCLUSION: Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes......AIMS: Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension...... and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. METHODS: In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study...

  16. Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension.

    Science.gov (United States)

    Nyberg, M; Mortensen, S P; Hellsten, Y

    2013-03-01

    Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study 2, young (23 ± 1 years, n = 8), older lifelong sedentary (66 ± 2 years, n = 8) and older lifelong endurance-trained (62 ± 2 years, n = 8) subjects were studied in a cross-sectional design. Skeletal muscle and plasma endothelin-1 levels were increased with age and plasma endothelin-1 levels were higher in hypertensive than normotensive individuals. Eight weeks of exercise training normalized plasma endothelin-1 levels in the hypertensive subjects and increased the protein expression of the ET(A) receptor in skeletal muscle of normotensive subjects. Similarly, individuals that had performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension. This effect may explain some of the beneficial effects of training on the cardiovascular system in older and hypertensive subjects. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

  17. Circulating thrombopoietin levels in normal healthy blood donors and in aplastic anemia patients in relation to disease severity

    Directory of Open Access Journals (Sweden)

    Abhay Singh

    2015-01-01

    Full Text Available Background: Thrombopoietin (TPO is the key hematopoietic growth factor regulating the production of platelets from bone marrow megakaryocytes and maintaining platelet hemostasis. This study was done to find any relationship between the levels of thrombopoietin and the severity of disease in patients with aplastic anemia. Materials and Methods: Serum samples were collected from 52 patients with a confirmed diagnosis of aplastic anemia and 45 normal healthy blood donors of both sexes over a period of 2 years, and TPO was estimated by using commercially available TPO-specific-enzyme-linked immunosorbent assay. Results: The median TPO level of 1190 pg/ml (range 625-7651 pg/ml in aplastic anemia patients was significantly higher than the median TPO level of 121.1 pg/ml (81.25-237.7 pg/ml in normal healthy blood donors (P = 0.000. No significant difference was observed in TPO levels of male and female patients (P = 0.453. The median TPO concentrations observed in very severe aplastic anemia, severe aplastic anemia, and nonsevere aplastic anemia were 2765 pg/ml (range 625-6451 pg/ml, 1190 pg/ml (range 672.1-7651 pg/ml, and 1111.5 pg/ml (range 761.1-2289.2 pg/ml, respectively. TPO in patients of very severe aplastic anemia was significantly higher than patients of nonsevere aplastic anemia (P = 0.043, with no significant relation among rest of the groups. Discussion: TPO levels in aplastic anemia patients were significantly higher than in healthy blood donors; however, in aplastic anemia patients TPO levels were significantly higher only in patients with very severe disease.

  18. Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas

    International Nuclear Information System (INIS)

    Haakensen, Vilde D; Børresen-Dale, Anne-Lise; Helland, Åslaug; Bjøro, Trine; Lüders, Torben; Riis, Margit; Bukholm, Ida K; Kristensen, Vessela N; Troester, Melissa A; Homen, Marit M; Ursin, Giske

    2011-01-01

    High serum levels of estradiol are associated with increased risk of postmenopausal breast cancer. Little is known about the gene expression in normal breast tissue in relation to levels of circulating serum estradiol. We compared whole genome expression data of breast tissue samples with serum hormone levels using data from 79 healthy women and 64 breast cancer patients. Significance analysis of microarrays (SAM) was used to identify differentially expressed genes and multivariate linear regression was used to identify independent associations. Six genes (SCGB3A1, RSPO1, TLN2, SLITRK4, DCLK1, PTGS1) were found differentially expressed according to serum estradiol levels (FDR = 0). Three of these independently predicted estradiol levels in a multivariate model, as SCGB3A1 (HIN1) and TLN2 were up-regulated and PTGS1 (COX1) was down-regulated in breast samples from women with high serum estradiol. Serum estradiol, but none of the differentially expressed genes were significantly associated with mammographic density, another strong breast cancer risk factor. In breast carcinomas, expression of GREB1 and AREG was associated with serum estradiol in all cancers and in the subgroup of estrogen receptor positive cases. We have identified genes associated with serum estradiol levels in normal breast tissue and in breast carcinomas. SCGB3A1 is a suggested tumor suppressor gene that inhibits cell growth and invasion and is methylated and down-regulated in many epithelial cancers. Our findings indicate this gene as an important inhibitor of breast cell proliferation in healthy women with high estradiol levels. In the breast, this gene is expressed in luminal cells only and is methylated in non-BRCA-related breast cancers. The possibility of a carcinogenic contribution of silencing of this gene for luminal, but not basal-like cancers should be further explored. PTGS1 induces prostaglandin E2 (PGE2) production which in turn stimulates aromatase expression and hence increases the

  19. High level extracellular production of a recombinant alkaline catalase in E. coli BL21 under ethanol stress and its application in hydrogen peroxide removal after cotton fabrics bleaching.

    Science.gov (United States)

    Yu, Zhenxiao; Zheng, Hongchen; Zhao, Xingya; Li, Shufang; Xu, Jianyong; Song, Hui

    2016-08-01

    The effects of induction parameters, osmolytes and ethanol stress on the productivity of the recombinant alkaline catalase (KatA) in Escherichia coli BL21 (pET26b-KatA) were investigated. The yield of soluble KatA was significantly enhanced by 2% ethanol stress. And a certain amount of Triton X-100 supplementation could markedly improved extracellular ratio of KatA. A total soluble catalase activity of 78,762U/mL with the extracellular ratio of 92.5% was achieved by fed-batch fermentation in a 10L fermentor, which was the highest yield so far. The purified KatA showed high stability at 50°C and pH 6-10. Application of KatA for elimination of H2O2 after cotton fabrics bleaching led to less consumption of water, steam and electric power by 25%, 12% and 16.7% respectively without productivity and quality losing of cotton fabrics. Thus, the recombinant KatA is a promising candidate for industrial production and applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Classification of Normal and Apoptotic Cells from Fluorescence Microscopy Images Using Generalized Polynomial Chaos and Level Set Function.

    Science.gov (United States)

    Du, Yuncheng; Budman, Hector M; Duever, Thomas A

    2016-06-01

    Accurate automated quantitative analysis of living cells based on fluorescence microscopy images can be very useful for fast evaluation of experimental outcomes and cell culture protocols. In this work, an algorithm is developed for fast differentiation of normal and apoptotic viable Chinese hamster ovary (CHO) cells. For effective segmentation of cell images, a stochastic segmentation algorithm is developed by combining a generalized polynomial chaos expansion with a level set function-based segmentation algorithm. This approach provides a probabilistic description of the segmented cellular regions along the boundary, from which it is possible to calculate morphological changes related to apoptosis, i.e., the curvature and length of a cell's boundary. These features are then used as inputs to a support vector machine (SVM) classifier that is trained to distinguish between normal and apoptotic viable states of CHO cell images. The use of morphological features obtained from the stochastic level set segmentation of cell images in combination with the trained SVM classifier is more efficient in terms of differentiation accuracy as compared with the original deterministic level set method.

  1. The Effect of Aspalathin on Levels of Sugar and Lipids in Streptozotocin-Induced Diabetic and Normal Rats

    Directory of Open Access Journals (Sweden)

    Mahmood Najafian

    2016-10-01

    Full Text Available Background Flavonoids have been reported as mammalian alpha-amylase inhibitors, a property which could be useful in the management of postprandial hyperglycemia in diabetes and its related disorders. Objectives In the present study the inhibitory effect of aspalathin as a flavonoid on alpha amylase activity and levels of sugar and lipids in rats, has been investigated. Methods In this experimental study, type inhibition of aspalatin on amylase and in the part of in vivo, the effect of aspalathin orally doses 5, 10, 20 and 40 mg/kg body weight on sugar and lipids levels was tested in a streptozotocin-induced model of diabetes and normal rats. The data were analyzed by one-sample Kolmogrov-Smirnov, Levene and ANOVA tests through SPSS version 22. Results The results showed that aspalathin is a competitive inhibitor for alpha amylase with Ki = 37.0 μM. In both diabetic and normal groups in all doses nearly dose dependent manner reduced blood glucose levels and beneficial effect on dyslipidemia were observed in diabetic rats, as well as reduction of disturbing consequences of diabetes such as high urine volume and water intake. Aspalathin was observed to have a weight loss-inductive effect, alongside with a reduction in food intake. Conclusions It seems that, this compound could be proposed as an antihyperglycemic and antihyperlipidemic agent in diabetes and potential therapeutic in obesity.

  2. Isolation and genetic analysis of Aspergillus niger mutants with reduced extracellular glucoamylase

    International Nuclear Information System (INIS)

    Valent, G.U.; Calil, M.R.; Bonatelli Junior, R.

    1992-01-01

    Mutants with impaired production of extracellular glucoamylase were isolated at a high frequency (2% of survivors) from an Aspergillus niger strain treated with UV light. These were designated as low glucoamylase producers (lgp, up to 30% of the parental yield) and medium producers (mgp, a 35 to 50% decrease in enzyme level). All the mutants were shown to be recessive; one strain segregated two unlinked genes. Complementation tests, and segregation from heterozygous diploid, suggested at least three to four unlinked genes, each able to impair glucoamylase production. There is evidence of a single structural gene for glucoamylase in A. niger. Therefore, as production of extracellular enzymes is normally the final result of several steps at intracellular and membrane levels, including regulation of enzyme synthesis, we suggest intergenic interaction that controls extracellular enzyme accumulation and that mutation in any of these genes would result in impaired production. (author)

  3. Normal values of glomerular filtration rate in geriatrics in Bandung and its correlation with serum cystatin-C levels

    International Nuclear Information System (INIS)

    Resnaldi, A.; Yuliani, A.; Hidayat, B.; Kartamihardja, A.H.S.

    2007-01-01

    Full text: Determination of the normal values of glomerular filtration rate (GFR) is an essential part of the evaluation of patient with kidney disease. GFR almost linearly decreases with age at a mean annual rate of 0.8 ml/min/1.73 m2 over the age of 30 years old. According to NHANES III mean GFR for population with age > 60 years was 80 mL/min/1.73 m2. It is recommended for each centre to determine their own normal values of GFR for different age groups particularly in geriatric population. Recently, serum cystatin-C has been proposed as a new endogenous marker of glomerular filtration rate. Aim of the study was to determination of normal values of glomerular filtration rate (GFR) in geriatrics in Bandung and its correlation with serum Cystatin-C levels. Subjects were 24 males and 36 females (mean age 66.71 ± 6.7 years; range 60-87 yrs), without any renal and/or systemic disease. Creatinine clearance was estimated by using Cockroft-Gault formula and serum cystatin-C level were determined by using particle enhanced immunonephelometric method, while GFR values were determined by external body counting methods using Tc-99m DTPA ( Gates' methods ). Pearson correlation was used to determine correlation between variables and a P value < 0.05 is considered significant. Results and Discussion. Mean total GFR was 67.57 ml/min/1.73 m2 (SD ± 16.02), range from 45 to 100 ml/min/1.73 m2. Mean total GFR for male was 69.46 ml/min/1.73 m2, and female was 66.31 ml/min/1.73 m2, the difference was statistically significant (p < 0.05). The results were lower than NHANES III values. There was a better correlation between total GFR and cystatin-C level (r = -0.522 and p < 0.001) compared to total GFR and creatinine clearance (r 0.306 and p < 0.005). Mean creatinine clearance was 57.93 ml/min and serum cystatin-C was 0.97 mg/dl, the correlation was statistically significant (r -0.414 and p < 0.005). Conclusions: The normal values of GFR in geriatric population in Bandung were 69

  4. A decreased soluble Klotho level with normal eGFR, FGF23, serum phosphate, and FEP in an ADPKD patient with enlarged kidneys due to multiple cysts.

    Science.gov (United States)

    Kanai, Takahiro; Shiizaki, Kazuhiro; Betsui, Hiroyuki; Aoyagi, Jun; Yamagata, Takanori

    2018-05-16

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder. ADPKD is characterized clinically by the presence of multiple bilateral renal cysts that lead to chronic renal failure. The cysts evolve from renal tubular epithelial cells that express the Klotho gene. Notably, Klotho acts as a co-receptor for fibroblast growth factor 23 (FGF23); in this context, it induces phosphaturia and maintains serum phosphate at a normal level. Many reports have shown that decreases in the soluble Klotho level and increases in the FGF23 level are associated with glomerular filtration rate (GFR) decline, but a recent study observed these changes in patient with normal eGFR. It remains unclear whether the decrease in the Klotho level precedes the increase in FGF23. Here, we present an ADPKD patient with enlarged kidneys due to multiple cysts who had a decreased soluble Klotho level but a normal eGFR and a normal FGF23 level. The patient's serum phosphate level was normal, as was the fractional excretion of phosphate (FEP). This appears to be the first reported case to show a decreased soluble Klotho level plus normal eGFR, FGF23, and FEP. These results suggest that Klotho decreases before FGF23 increases and further suggest that Klotho is not required to maintain normal serum phosphate levels in ADPKD if the FEP and serum phosphate levels are normal.

  5. Real-time monitoring of extracellular l-glutamate levels released by high-frequency stimulation at region CA1 of hippocampal slices with a glass capillary-based l-glutamate sensor

    Directory of Open Access Journals (Sweden)

    Yuki Ikegami

    2014-12-01

    Full Text Available Real-time monitoring of l-glutamate released by high-frequency stimulation in region CA1 of mouse hippocampal slices was performed with a glass capillary-based sensor, in combination with the recoding of excitatory postsynaptic potentials (fEPSPs. A method for extracting l-glutamate currents from the recorded ones was described and applied for determining the level of extracellular l-glutamate released by 100 Hz stimulation. Recording of an l-glutamate current with a current sampling interval of 1 Hz was found to be useful for acquiring a Faradaic current that reflects l-glutamate level released by the high-frequency stimulation of 7 trains, each 20 stimuli at 100 Hz and inter-train interval of 3 s. The l-glutamate level was obtained as 15 ± 6 μM (n = 8 for the persistent enhancement of fEPSPs, i.e., the induction of long-term potentiation (LTP, and 3 ± 1 μM (n = 5 for the case of no LTP induction. Based on these observations, the level of the extracellular l-glutamate was shown to play a crucial role in the induction of LTP.

  6. What Are Normal Metal Ion Levels After Total Hip Arthroplasty? A Serologic Analysis of Four Bearing Surfaces.

    Science.gov (United States)

    Barlow, Brian T; Ortiz, Philippe A; Boles, John W; Lee, Yuo-Yu; Padgett, Douglas E; Westrich, Geoffrey H

    2017-05-01

    The recent experiences with adverse local tissue reactions have highlighted the need to establish what are normal serum levels of cobalt (Co), chromium (Cr), and titanium (Ti) after hip arthroplasty. Serum Co, Cr, and Ti levels were measured in 80 nonconsecutive patients with well-functioning unilateral total hip arthroplasty and compared among 4 bearing surfaces: ceramic-on-ceramic (CoC); ceramic-on-polyethylene (CoP); metal-on-polyethylene (MoP), and dual mobility (DM). The preoperative and most recent University of California, Los Angeles (UCLA) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were compared among the different bearing surfaces. No significant difference was found among serum Co and Cr levels between the 4 bearing surface groups (P = .0609 and P = .1577). Secondary analysis comparing metal and ceramic femoral heads demonstrated that the metal group (MoP, modular dual mobility (Stryker Orthopedics, Mahwah, NJ) [metal]) had significant higher serum Co levels compared with the ceramic group (CoC, CoP, MDM [ceramic]) (1.05 mg/L ± 1.25 vs 0.59 mg/L ± 0.24; P = .0411). Spearman coefficient identified no correlation between metal ion levels and patient-reported outcome scores. No serum metal ion level differences were found among well-functioning total hip arthroplasty with modern bearing couples. Significantly higher serum Co levels were seen when comparing metal vs ceramic femoral heads in this study and warrants further investigation. Metal ion levels did not correlate with patient-reported outcome measures. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Association of plasma fatty acid composition with plasma irisin levels in normal weight and overweight/obese children.

    Science.gov (United States)

    Viitasalo, A; Ågren, J; Venäläinen, T; Pihlajamäki, J; Jääskeläinen, J; Korkmaz, A; Atalay, M; Lakka, T A

    2016-08-01

    Irisin has been suggested to protect against overweight. There are no previous data on the association of plasma fatty acid (FA) composition with plasma irisin. We studied the association of FA composition with plasma irisin in normal weight and overweight/obese children. This cross-sectional study included pre-pubertal children (388 normal weight children and 55 overweight/obese children); 6-9 years of age, taking part in the Physical Activity and Nutrition in Children Study. After an overnight fast, we measured plasma FA composition by gas chromatography and plasma irisin levels by enzyme-linked immunosorbent assay. Higher proportion of total monounsaturated fatty acids in plasma cholesteryl esters (CEs) (β = 0.139, P = 0.003) and phospholipids (PLs) (β = 0.147, P = 0.002) and lower proportion of total polyunsaturated fatty acids in plasma CE (β = -0.130, P = 0.006) and PL (β = -0.165, P overweight/obese children compared to normal weight children. Higher proportion of γ-linolenic acid (β = 0.324, P = 0.017) and lower proportion of linoleic acid (β = -0.397, P = 0.005) in plasma CE were related to higher plasma irisin level among overweight/obese children, indicating the direct association of estimated D6D activity in plasma CE (β = 0.343, P = 0.011) with plasma irisin. Furthermore, higher proportion of oleic acid in plasma CE (β = 0.345, P = 0.012) and PL (β = 0.292, P = 0.033) and higher proportion of adrenic acid (β = 0.366, P = 0.008) and docosapentaenoic acid (β = 0.351, P = 0.010) in plasma PL were associated with higher plasma irisin level among overweight/obese children. Metabolically unfavourable plasma FA profile was associated with higher plasma irisin level especially in overweight/obese children, suggesting that excess body fat might modulate these relationships. © 2015 World Obesity.

  8. Normalization of pH level and gastric mucosa after eradication of H. pylori in the remnant stomach.

    Science.gov (United States)

    Kato, Shunji; Matsukura, Norio; Matsuda, Noriko; Tsuchiya, Shinichi; Naito, Zenya; Tajiri, Takashi

    2008-12-01

    The Updated Sydney System (USS) is used to evaluate chronic gastritis and chronic atrophic gastritis (CAG) due to H. pylori infection. Here, we investigated USS scores and gastric juice pH levels in H. pylori infection-positive or -eradicated patients with remnant stomach after surgery. Gastric juice pH levels were measured using pH test-tape in 197 patients (112 H. pylori-positive and 85 H. pylori-negative after eradication) who had undergone distal gastrectomy and conventional H. pylori eradication therapy. In H. pylori infection-positive remnant stomach cases, gastric juice pH showed a reverse correlation with pepsinogen I/II ratio, and H. pylori infection-negative patients following eradication showed associations with the degree of atrophy and intestinal metaplasia at both the anastomosis and in the corpus. Further, pH levels in these patients were normalized time depending after the eradication in the remnant stomach. Eradication therapy for the remnant stomach contributes to the possible improvement of stomach conditions by controlling the pH level of gastric juice. This effect will be protective against the risk of secondary stomach carcinogenesis in the remnant stomach.

  9. Normal and reversed supramolecular chirality of insulin fibrils probed by vibrational circular dichroism at the protofilament level of fibril structure.

    Science.gov (United States)

    Kurouski, Dmitry; Dukor, Rina K; Lu, Xuefang; Nafie, Laurence A; Lednev, Igor K

    2012-08-08

    Fibrils are β-sheet-rich aggregates that are generally composed of several protofibrils and may adopt variable morphologies, such as twisted ribbons or flat-like sheets. This polymorphism is observed for many different amyloid associated proteins and polypeptides. In a previous study we proposed the existence of another level of amyloid polymorphism, namely, that associated with fibril supramolecular chirality. Two chiral polymorphs of insulin, which can be controllably grown by means of small pH variations, exhibit opposite signs of vibrational circular dichroism (VCD) spectra. Herein, using atomic force microscopy (AFM) and scanning electron microscopy (SEM), we demonstrate that indeed VCD supramolecular chirality is correlated not only by the apparent fibril handedness but also by the sense of supramolecular chirality from a deeper level of chiral organization at the protofilament level of fibril structure. Our microscopic examination indicates that normal VCD fibrils have a left-handed twist, whereas reversed VCD fibrils are flat-like aggregates with no obvious helical twist as imaged by atomic force microscopy or scanning electron microscopy. A scheme is proposed consistent with observed data that features a dynamic equilibrium controlled by pH at the protofilament level between left- and right-twist fibril structures with distinctly different aggregation pathways for left- and right-twisted protofilaments. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  10. On combining multi-normalization and ancillary measures for the optimal score level fusion of fingerprint and voice biometrics

    Science.gov (United States)

    Mohammed Anzar, Sharafudeen Thaha; Sathidevi, Puthumangalathu Savithri

    2014-12-01

    In this paper, we have considered the utility of multi-normalization and ancillary measures, for the optimal score level fusion of fingerprint and voice biometrics. An efficient matching score preprocessing technique based on multi-normalization is employed for improving the performance of the multimodal system, under various noise conditions. Ancillary measures derived from the feature space and the score space are used in addition to the matching score vectors, for weighing the modalities, based on their relative degradation. Reliability (dispersion) and the separability (inter-/intra-class distance and d-prime statistics) measures under various noise conditions are estimated from the individual modalities, during the training/validation stage. The `best integration weights' are then computed by algebraically combining these measures using the weighted sum rule. The computed integration weights are then optimized against the recognition accuracy using techniques such as grid search, genetic algorithm and particle swarm optimization. The experimental results show that, the proposed biometric solution leads to considerable improvement in the recognition performance even under low signal-to-noise ratio (SNR) conditions and reduces the false acceptance rate (FAR) and false rejection rate (FRR), making the system useful for security as well as forensic applications.

  11. Normalization of serum testosterone levels in patients treated with neoadjuvant hormonal therapy and three-dimensional conformal radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Padula, Gilbert D.A.; Zelefsky, Michael J.; Venkatraman, Ennapadam S.; Fuks, Zvi; Lee, Henry J.; Natale, Linda; Leibel, Steven A.

    2002-01-01

    Purpose: To determine the expected time to serum testosterone normalization after short-course neoadjuvant androgen deprivation therapy (NAAD) and three-dimensional conformal radiotherapy for patients with localized prostate cancer and to identify pretreatment predictors that correlated with the time to testosterone normalization. Methods: Between 1993 and 1999, 88 patients with localized prostate cancer, treated with NAAD and external beam radiotherapy, were prospectively monitored after treatment with sequential testosterone levels. NAAD was administered before and during the entire course of radiotherapy and discontinued at the end of treatment. The median duration of NAAD was 6 months. The actuarial rate of serum testosterone normalization from the end of treatment was evaluated, and the presence or absence of androgen deprivation-related symptoms was correlated with serum testosterone levels. Symptoms assessed included weight gain, loss of libido, breast tenderness, breast enlargement, hot flashes, and fatigue. Results: Serum testosterone levels returned to the normal range in 57 (65%) of the 88 patients and failed to normalize in 31 patients (35%). The median time to normalization was 18.3 months. The actuarial rate of normalization at 3, 6, 12, and 24 months was 10%, 26%, 38%, and 59%, respectively. In a multivariate analysis, a pretreatment testosterone level in the lower range of normal was the only variable that predicted for delayed testosterone normalization after NAAD (p=0.00047). Among 45 patients with information concerning androgen deprivation-related symptoms recorded 1 year after cessation of NAAD, 24 (53%) had normalized testosterone levels, but in 21 patients (47%), the levels had not yet returned to normal. At 1 year, only 1 (4%) of 24 patients whose testosterone level had returned to normal experienced NAAD-related symptoms compared with 14 (67%) of 21 patients who did not have normal testosterone levels (p<0.001). Conclusion: Testosterone

  12. Some case studies of skewed (and other ab-normal) data distributions arising in low-level environmental research

    International Nuclear Information System (INIS)

    Currie, L.A.

    2001-01-01

    Three general classes of skewed data distributions have been encountered in research on background radiation, chemical and radiochemical blanks, and low levels of 85 Kr and 14 C in the atmosphere and the cryosphere. The first class of skewed data can be considered to be theoretically, or fundamentally skewed. It is typified by the exponential distribution of inter-arrival times for nuclear counting events for a Poisson process. As part of a study of the nature of low-level (anti-coincidence) Geiger- Mueller counter background radiation, tests were performed on the Poisson distribution of counts, the uniform distribution of arrival times, and the exponential distribution of inter-arrival times. The real laboratory system, of course, failed the (inter-arrival time) test - for very interesting reasons, linked to the physics of the measurement process. The second, computationally skewed, class relates to skewness induced by non-linear transformations. It is illustrated by non-linear concentration estimates from inverse calibration, and bivariate blank corrections for low-level 14 C- 12 C aerosol data that led to highly asymmetric uncertainty intervals for the biomass carbon contribution to urban ''soot''. The third, environmentally skewed, data class relates to a universal problem for the detection of excursions above blank or baseline levels: namely, the widespread occurrence of ab-normal distributions of environmental and laboratory blanks. This is illustrated by the search for fundamental factors that lurk behind skewed frequency distributions of sulfur laboratory blanks and 85 Kr environmental baselines, and the application of robust statistical procedures for reliable detection decisions in the face of skewed isotopic carbon procedural blanks with few degrees of freedom. (orig.)

  13. Some case studies of skewed (and other ab-normal) data distributions arising in low-level environmental research.

    Science.gov (United States)

    Currie, L A

    2001-07-01

    Three general classes of skewed data distributions have been encountered in research on background radiation, chemical and radiochemical blanks, and low levels of 85Kr and 14C in the atmosphere and the cryosphere. The first class of skewed data can be considered to be theoretically, or fundamentally skewed. It is typified by the exponential distribution of inter-arrival times for nuclear counting events for a Poisson process. As part of a study of the nature of low-level (anti-coincidence) Geiger-Muller counter background radiation, tests were performed on the Poisson distribution of counts, the uniform distribution of arrival times, and the exponential distribution of inter-arrival times. The real laboratory system, of course, failed the (inter-arrival time) test--for very interesting reasons, linked to the physics of the measurement process. The second, computationally skewed, class relates to skewness induced by non-linear transformations. It is illustrated by non-linear concentration estimates from inverse calibration, and bivariate blank corrections for low-level 14C-12C aerosol data that led to highly asymmetric uncertainty intervals for the biomass carbon contribution to urban "soot". The third, environmentally, skewed, data class relates to a universal problem for the detection of excursions above blank or baseline levels: namely, the widespread occurrence of ab-normal distributions of environmental and laboratory blanks. This is illustrated by the search for fundamental factors that lurk behind skewed frequency distributions of sulfur laboratory blanks and 85Kr environmental baselines, and the application of robust statistical procedures for reliable detection decisions in the face of skewed isotopic carbon procedural blanks with few degrees of freedom.

  14. High-fructose corn syrup and sucrose have equivalent effects on energy-regulating hormones at normal human consumption levels.

    Science.gov (United States)

    Yu, Zhiping; Lowndes, Joshua; Rippe, James

    2013-12-01

    Intake of high-fructose corn syrup (HFCS) has been suggested to contribute to the increased prevalence of obesity, whereas a number of studies and organizations have reported metabolic equivalence between HFCS and sucrose. We hypothesized that HFCS and sucrose would have similar effects on energy-regulating hormones and metabolic substrates at normal levels of human consumption and that these values would not change over a 10-week, free-living period at these consumption levels. This was a randomized, prospective, double-blind, parallel group study in which 138 adult men and women consumed 10 weeks of low-fat milk sweetened with either HFCS or sucrose at levels of the 25th, 50th, and 90th percentile population consumption of fructose (the equivalent of 40, 90, or 150 g of sugar per day in a 2000-kcal diet). Before and after the 10-week intervention, 24-hour blood samples were collected. The area under the curve (AUC) for glucose, insulin, leptin, active ghrelin, triglyceride, and uric acid was measured. There were no group differences at baseline or posttesting for all outcomes (interaction, P > .05). The AUC response of glucose, active ghrelin, and uric acid did not change between baseline and posttesting (P > .05), whereas the AUC response of insulin (P < .05), leptin (P < .001), and triglyceride (P < .01) increased over the course of the intervention when the 6 groups were averaged. We conclude that there are no differences in the metabolic effects of HFCS and sucrose when compared at low, medium, and high levels of consumption. © 2013 Elsevier Inc. All rights reserved.

  15. Energy information needs for U. S. state-level policy making: Minimal data requirements during normal and emergency periods

    Energy Technology Data Exchange (ETDEWEB)

    Barkenbus, J.N.; Leff, H.S.

    1983-01-01

    Since the oil embargo of 1973, state governments have increased their efforts to track and understand energy flows within their boundaries. There is a commonly perceived need to comprehend the status of present and expected future energy availability, demand, and price and to be prepared to exercise responsible and effective management during energy emergencies. This responsibility has brought with it new needs for accurate and timely state-level information on energy transactions and the external parameters that effect energy availability and disposition. What energy data are needed by a state, regardless of its idiosyncracies, during both normal and energy emergency periods, and to what extent are these data available now. The authors find that needed ongoing (core) data are only partially available at present, and that emergency data can be obtained only with a carefully planned monitoring program that can be fitted to specific emergency conditions. Overall, this paper provides a realistic assessment of the state-level energy data needed to provide state policy makers with sufficient information to make considered judgments.

  16. Energy-information needs for US state-level policy making: minimal data requirements during normal and emergency periods

    Energy Technology Data Exchange (ETDEWEB)

    Barkenbus, J.N.; Leff, H.S.

    1983-01-01

    Since the oil embargo of 1973, state governments have increased their efforts to track and understand energy flows within their boundaries. There is a commonly perceived need to comprehend the status of present and expected future energy availability, demand, and price and to be prepared to exercise responsible and effective management during energy emergencies. This responsibility has brought with it new needs for accurate and timely state-level information on energy transactions and the external parameters that effect energy availability and disposition. Hence, we ask: what energy data are needed by a state, regardless of its idiosyncracies, during both normal and energy emergency periods, and to what extent are these data available now. We find that needed ongoing (core) data are only partially available at present, and that emergency data can be obtained only with a carefully planned monitoring program that can be fitted to specific emergency conditions. Overall, this paper provides a realistic assessment of the state-level energy data needed to provide state policy makers with sufficient information to make considered judgments. 7 references, 6 tables.

  17. Forced swimming test and fluoxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes.

    Science.gov (United States)

    Bianchi, M; Moser, C; Lazzarini, C; Vecchiato, E; Crespi, F

    2002-03-01

    Low levels of central serotonin (5-HT) have been related to the state of depression, and 5-HT is the major target of the newer antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). Neurons and platelets display structural and functional similarities, so that the latter have been proposed as a peripheral model of central functions. In particular, in blood more than 99% of 5-HT is contained in platelets, so that one could consider changes in 5-HT levels in platelets as a mirror of changes in central 5-HT. Here, this hypothesis has been studied via the analysis of the influence of: (1) the forced swimming test (FST, which has been proved to be of utility to predict the clinical efficacy of antidepressants in rodents) and (2) treatment with the SSRI fluoxetine upon 5-HT levels monitored in brain regions and in peripheral platelets by means of electrochemical in vivo and ex vivo measurements. The results obtained confirm that the FST increases immobility; furthermore they show a parallel and significant decrease in cerebral (brain homogenate) and peripheral (in platelet-rich plasma, PRP) voltammetric 5-HT levels following the FST in naive rats. In addition, subchronic treatment with fluoxetine was followed by a significant increase in 5-HT levels in PRP, while the same SSRI treatment performed within the FST resulted in a decrease in the 5-HT levels in PRP. However, this decrease was inferior to that observed without SSRI treatment. These data suggest that there is an inverse relationship between immobility and the levels of 5-HT in PRP and that these peripheral 5-HT levels are sensitive to: (1) the FST, (2) the treatment with fluoxetine and (3) the combination of both treatments, i.e. SSRI + FST. It has been reported that SSRI treatment at first inhibits the 5-HT transporter in brain, resulting in increased extracellular 5-HT, while following sustained SSRI treatments decreased intracellular levels of central 5-HT were observed. Accordingly, the

  18. An efficient approach for differentiating Alzheimer's disease from normal elderly based on multicenter MRI using gray-level invariant features.

    Directory of Open Access Journals (Sweden)

    Muwei Li

    Full Text Available Machine learning techniques, along with imaging markers extracted from structural magnetic resonance images, have been shown to increase the accuracy to differentiate patients with Alzheimer's disease (AD from normal elderly controls. Several forms of anatomical features, such as cortical volume, shape, and thickness, have demonstrated discriminative capability. These approaches rely on accurate non-linear image transformation, which could invite several nuisance factors, such as dependency on transformation parameters and the degree of anatomical abnormality, and an unpredictable influence of residual registration errors. In this study, we tested a simple method to extract disease-related anatomical features, which is suitable for initial stratification of the heterogeneous patient populations often encountered in clinical data. The method employed gray-level invariant features, which were extracted from linearly transformed images, to characterize AD-specific anatomical features. The intensity information from a disease-specific spatial masking, which was linearly registered to each patient, was used to capture the anatomical features. We implemented a two-step feature selection for anatomic recognition. First, a statistic-based feature selection was implemented to extract AD-related anatomical features while excluding non-significant features. Then, seven knowledge-based ROIs were used to capture the local discriminative powers of selected voxels within areas that were sensitive to AD or mild cognitive impairment (MCI. The discriminative capability of the proposed feature was measured by its performance in differentiating AD or MCI from normal elderly controls (NC using a support vector machine. The statistic-based feature selection, together with the knowledge-based masks, provided a promising solution for capturing anatomical features of the brain efficiently. For the analysis of clinical populations, which are inherently heterogeneous

  19. Comparison of low-normal and high-normal IGF-1 target levels during growth hormone replacement therapy : A randomized clinical trial in adult growth hormone deficiency

    NARCIS (Netherlands)

    van Bunderen, Christa C; Lips, Paul; Kramer, Mark H H; Drent, Madeleine L

    BACKGROUND: Current guidelines state that the goals of growth hormone (GH) therapy in adults should be an appropriate clinical response, avoidance of side effects, and an IGF-1 value within the age-adjusted reference range. There are no published studies on the target level for IGF-1 that offer

  20. Effect of dopamine, dopamine D-1 and D-2 receptor modulation on ACTH and cortisol levels in normal men and women

    DEFF Research Database (Denmark)

    Boesgaard, S; Hagen, C; Andersen, A N

    1990-01-01

    The regulation of the hypothalamic-pituitary-adrenal axis by dopamine is not fully understood. Therefore, we have studied the effect of dopamine, metoclopramide, a D-2 receptor antagonist, and fenoldopam, a specific D-1 receptor agonist, on ACTH and cortisol levels in normal subjects. Normal women...

  1. The value of CT measurement of normal human mandible, hyoid and the airway area at the hyoid level

    International Nuclear Information System (INIS)

    Chen Changliang; Zhang Jia; Ge Pingjiang; Zhang Siyi

    2004-01-01

    Objective: To determine the normal value and clinical significance of the lengths and angles of both mandible and hyoid, and their relationship with cervical vertebra as well as the transverse area of the airway at the hyoid level using CT. Methods: Several lines and angles on the CT images were measured in 68 normal subjects. Line A was the length between both free ends of the mandible; line B was the distance from the body of the mandible to line A; Line C was the distance from line A to the anterior aspect of the cervical vertebra. α 1 was the angle between the middle of mandible body and its two free ends. Line a was the distance between two free ends of greater horn of hyoid bone. Line b was the distance from hyoid to line a. Line c was the distance from line a to the cervical vertebra. α 2 was the angle between the middle of hyoid body and its two free ends. S stood for the area of the airway at the hyoid level. SPSS 11.5 statistical analysis package was used to analyze the results. Results: The average and median distance/angle of various measurements were as follows: line A was (89.28±5.90) mm and 88.70 mm, line B was (62.61±5.78) mm and 62.50 mm, line C was (9.29±3.29) mm and 4.20 mm, α 1 was (71.25±6.77) degree and 71.05 degree, line a was (38.69 ± 6.07) mm and 39.90 mm, line b was (28.79 ± 4.37) mm and 28.50 mm, line c was (1.91 ± 3.03) mm and 1.75 mm, α 2 was (68.47 ± 15.71) degree and 66.95 degree. The average S was (436.14 ± 160.37) mm 2 and median was 431.75 mm 2 . Conclusion: It is easy to measure the three lines and the two angles of mandible and hyoid. The measurement is of vital importance in the diagnosis and treatment for obstructive sleep apnea syndrome

  2. Hair removal in hirsute women with normal testosterone levels: a randomized controlled trial of long-pulsed diode laser vs. intense pulsed light

    DEFF Research Database (Denmark)

    Haak, C S; Jensen, Pernille Nymann; Pedersen, A T

    2010-01-01

    Hirsutism is a common disorder in women of reproductive age, and androgen disturbances may aggravate the condition. Limited evidence exists regarding efficacy of hair removal in this specific population and no data are available for patients with verified normal testosterone levels.......Hirsutism is a common disorder in women of reproductive age, and androgen disturbances may aggravate the condition. Limited evidence exists regarding efficacy of hair removal in this specific population and no data are available for patients with verified normal testosterone levels....

  3. Mechanical muscle function and lean body mass during supervised strength training and testosterone therapy in aging men with low-normal testosterone levels

    DEFF Research Database (Denmark)

    Kvorning, Thue; Christensen, Louise L; Madsen, Klavs

    2013-01-01

    To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass (LBM) in aging men with low-normal testosterone levels in a randomized, double-blind, placebo-controlled 24-week study.......To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass (LBM) in aging men with low-normal testosterone levels in a randomized, double-blind, placebo-controlled 24-week study....

  4. Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors.

    Science.gov (United States)

    Fernández-Friera, Leticia; Fuster, Valentín; López-Melgar, Beatriz; Oliva, Belén; García-Ruiz, José M; Mendiguren, José; Bueno, Héctor; Pocock, Stuart; Ibáñez, Borja; Fernández-Ortiz, Antonio; Sanz, Javier

    2017-12-19

    Absence of cardiovascular risk factors (CVRFs) is traditionally considered low risk for atherosclerosis; however, individuals without CVRFs, as currently defined, still have events. This study sought to identify predictors of subclinical atherosclerosis in CVRF-free individuals. Participants from the PESA (Progression of Early Subclinical Atherosclerosis) study (n = 4,184) without conventional CVRFs were evaluated (n = 1,779; 45.0 ± 4.1 years, 50.3% women). CVRF freedom was defined as no current smoking and untreated blood pressure cholesterol cholesterol (LDL-C) cholesterol ≥40 mg/dl. A subgroup with optimal CVRFs (n = 740) was also defined as having blood pressure cholesterol LDL-C was independently associated with atherosclerosis presence and extent, in both the CVRF-free and CVRF-optimal groups (odds ratio [×10 mg/dl]: 1.14 to 1.18; p LDL-C, even at levels currently considered normal, is independently associated with the presence and extent of early systemic atherosclerosis in the absence of major CVRFs. These findings support more effective LDL-C lowering for primordial prevention, even in individuals conventionally considered at optimal risk. (Progression of Early Subclinical Atherosclerosis [PESA] Study; NCT01410318). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Study of genetic variation at the level of DNA between normal and sterilized potato tuber moth males (phthorimaea operculella, zeller)

    International Nuclear Information System (INIS)

    Ammouneh, H.; Makee, H.; Idris, E.

    2009-06-01

    The main objective of current study was to determine the genetic variation at the level of DNA between the normal and sterilized potato tuber moth males. The required mating experiments were carried out to obtain partially sterilized males at 150 Gy and their offspring. Some biological factors of these males were estimated and compared to their unirradiated siblings. To acquire good quality and quantity of DNA for the AFLP technique, several methods were undertaken to isolate DNA of potato tuber moth male from different developmental stages especially from adult stage. However, a method called Modified M5 was used. By Modified M5, which required phenol for the isolation of DNA, in some samples 8 to 12 μg were obtained from one insect with 95-100% purity. In our study, AFLP technique was used to analyze the DNA samples of irradiated and unirradiated males from required mating. The result analysis showed that there was a clear genetic variability between examined individuals. However, the relationship between unirradiated F1 and F2 males was stronger than that between irradiated males. Thus, our result demonstrates that the AFLP could be efficiently utilized for studying genetic variation between insect species or between individuals of the same line which have biological differences induced by several factors such as irradiation. Moreover, this technique could enhance the effectiveness of sterile insect technique by using the AFLP in the monitoring system of released insects. (author)

  6. Study Of Genetic Variation At The Level Of DNA Between Normal And Steriled Potato Tuber Moth Males (Phthorimaea operculella, Zeller)

    International Nuclear Information System (INIS)

    Ammouneh, H.; Makee, H.; Idris, E.

    2010-01-01

    The main objective of current study was to determine the genetic variation at the level of DNA between the normal and sterilized potato tuber moth males. The required mating experiments were carried out to obtain partially sterilize males at 150 Gy and their offspring. Some biological factors of these males were estimated and compared to their unirradiated siblings. To acquire good quality and quantity of DNA for the AFLP technique, several methods were undertaken to isolate DNA of potato tuber moth male from different developmental stages especially from adult stage. However, a method called Modified M5 was used. By Modified M5, which required phenol for the isolation of DNA, in some samples 8 to 12 Mg were obtained from one insect with 95-100% purity. In our study, AFLP technique was used to analyze the DNA samples of irradiated and unirradiated males from required mating. The result analysis showed that there was a clear genetic variability between examined individuals. However, the relationship between unirradiated F1 and F2 males was stronger than that between irradiated males. Thus, our result demonstrates that the AFLP could be efficiently utilized for studying genetic variation between insect species or between individuals of the same line which have biological differences induced by several factors such as irradiation. Moreover, this technique could enhance the effectiveness of sterile insect technique by using the AFLP in the monitoring system of released insects. (author)

  7. Diagnostic value of blood lipids testing in patients with high-normal and subclinical levels of TSH in prevention and treatment of dislipoproteinemia

    Directory of Open Access Journals (Sweden)

    O D Rymar

    2010-12-01

    Full Text Available The purpose of the study is to evaluate character of lipid profile changes in Novosibirsk populational sample of men and women (45–69 years with subclinical and high-normal TSH levels. Current study was performed within the HAPIEE project “Determinants of cardiovascular diseases in Eastern Europe” of the Welcome Trust fond. Populational subsample of 280 subjects (125 men (44.6% and 155 women (55.4% was analyzed. Received data showed that high-normal TSH levels within 1.71–4.05 mIU/l have been associated with higher levels of triglycerides, total cholesterol and LDL cholesterol, compared with low-normal TSH levels 0.17–0.47 mIU/l (р<0.05. Women with subclinical hypothyroidism had significantly higher average levels of total cholesterol and LDL cholesterol compared with women without thyroid disorders.

  8. Serum Alanine Aminotransferase Levels within Normal Range Have Different Associations with Augmentation Index and Other Cardiometabolic Risk Factors in Nondrinkers and Drinkers: A Chinese Community-Based Analysis

    Directory of Open Access Journals (Sweden)

    Shihui Fu

    2017-01-01

    Full Text Available Background. To investigate whether serum alanine aminotransferase (ALT levels within normal range were associated with augmentation index (AIx and cardiometabolic risk factors in nondrinkers and drinkers in Chinese community-dwelling population. Methods. There were 4165 participants with serum ALT levels within normal range. Results. Alcohol drinking was observed in 1173 participants (28.2%. In multivariate analysis, serum ALT levels of nondrinkers were independently associated with age, sex, body mass index (BMI, hypertension, diabetes mellitus, diastolic blood pressure, triglyceride, low-density lipoprotein-cholesterol (LDL-c, and AIx, while serum ALT levels of drinkers were independently associated with age, sex, BMI, triglyceride, and LDL-c (p<0.05 for all. Conclusions. Associations of serum ALT levels within normal range with age, sex, body height and weight, and blood lipid were simultaneously present in participants with and without alcohol drinking, while associations of serum ALT levels within normal range with AIx, blood pressure, and glucose were seen in nondrinkers rather than in drinkers. These findings not only provide the evidence that serum ALT levels, even within the normal range, have different associations with arteriosclerosis and cardiometabolic risk factors in nondrinkers and drinkers but also are helpful in understanding the underlying pathophysiologic mechanisms linking the hepatic function to arteriosclerosis and cardiometabolic risk factors.

  9. Peroxidase enzymes regulate collagen extracellular matrix biosynthesis.

    Science.gov (United States)

    DeNichilo, Mark O; Panagopoulos, Vasilios; Rayner, Timothy E; Borowicz, Romana A; Greenwood, John E; Evdokiou, Andreas

    2015-05-01

    Myeloperoxidase and eosinophil peroxidase are heme-containing enzymes often physically associated with fibrotic tissue and cancer in various organs, without any direct involvement in promoting fibroblast recruitment and extracellular matrix (ECM) biosynthesis at these sites. We report herein novel findings that show peroxidase enzymes possess a well-conserved profibrogenic capacity to stimulate the migration of fibroblastic cells and promote their ability to secrete collagenous proteins to generate a functional ECM both in vitro and in vivo. Mechanistic studies conducted using cultured fibroblasts show that these cells are capable of rapidly binding and internalizing both myeloperoxidase and eosinophil peroxidase. Peroxidase enzymes stimulate collagen biosynthesis at a post-translational level in a prolyl 4-hydroxylase-dependent manner that does not require ascorbic acid. This response was blocked by the irreversible myeloperoxidase inhibitor 4-amino-benzoic acid hydrazide, indicating peroxidase catalytic activity is essential for collagen biosynthesis. These results suggest that peroxidase enzymes, such as myeloperoxidase and eosinophil peroxidase, may play a fundamental role in regulating the recruitment of fibroblast and the biosynthesis of collagen ECM at sites of normal tissue repair and fibrosis, with enormous implications for many disease states where infiltrating inflammatory cells deposit peroxidases. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. MR imaging of intracellular and extracellular deoxyhemoglobin

    International Nuclear Information System (INIS)

    Janick, P.A.; Grossman, R.I.; Asakura, T.

    1989-01-01

    MR imaging was performed on varying concentrations of intracellular and extracellular deoxyhemoglobin as well as varying proportions of deoxyhemoglobin and oxyhemoglobin in vitro at 1.5T with use of standard spin-echo and gradient-refocused spin sequences. This study indicates that susceptibility-induced T2 shortening occurs over a broad range of intracellular deoxyhemoglobin concentrations (maximal at hematocrits between 20% and 45%), reflecting diffusional effects at the cellular level. T2* gradient-echo imaging enhances the observed hypointensity in images of intracellular deoxyhemoglobin. The characteristic MR appearance of acute hemotomas can be modeled by the behavior of intracellular and extracellular deoxyhemoglobin and oxyhemoglobin

  11. Extracellular Gd-CA

    DEFF Research Database (Denmark)

    Thomsen, Henrik S; Marckmann, Peter

    2008-01-01

    Until recently it was believed that extracellular gadolinium-based contrast agents were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some gadolinium-based contrast agents may trig the development...... gadolinium-based agent (3-7% versus 0-1% per injection) in patients with reduced renal function. Prevalence after exposure to two gadodiamide injections is as high as 36% in patients with chronic kidney disease (CKD) stage 5. No report of NSF after the most stable agents has been reported in the peer...

  12. Development of a radioimmunoassay for pregnancy-associated plasma protein A and establishment of normal levels in the first trimester of pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Anthony, F; Masson, G M; Wood, P J [Southampton Univ. (UK)

    1983-01-01

    An accelerated double antibody method has been developed for the radioimmunoassay of pregnancy-associated plasma protein A (PAPP-A) in serum. The workable range for the assay was 0.4-1.8 mg/l of serum. PAPP-A levels were determined in single serum samples from 110 women with prospective normal pregnancies of between 7 and 14 weeks' gestation. The level of pregnancy specific ..beta../sub 1/ glycoprotein (SP/sub 1/) was also measured in these samples and normal ranges for PAPP-P and SP/sub 1/ were constructed from the results obtained.

  13. Development of a radioimmunoassay for pregnancy-associated plasma protein A and establishment of normal levels in the first trimester of pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Anthony, F; Masson, G M; Wood, P J [Southampton Univ. (UK)

    1983-01-01

    An accelerated double antibody method has been developed for the radioimmunoassay of pregnancy-associated plasma protein A (PAPP-A) in serum. The workable range for the assay was 0.04-1.8 mg/l of serum. PAPP-A levels were determined in single serum samples from 110 women with prospective normal pregnancies of between 7 and 14 weeks' gestation. The level of pregnancy specific ..beta../sub 1/ glycoprotein (SP/sub 1/) was also measured in these samples and normal ranges for PAPP-A and SP/sub 1/ were constructed from the results obtained.

  14. Development of a radioimmunoassay for pregnancy-associated plasma protein A and establishment of normal levels in the first trimester of pregnancy

    International Nuclear Information System (INIS)

    Anthony, F.; Masson, G.M.; Wood, P.J.

    1983-01-01

    An accelerated double antibody method has been developed for the radioimmunoassay of pregnancy-associated plasma protein A (PAPP-A) in serum. The workable range for the assay was 0.4-1.8 mg/l of serum. PAPP-A levels were determined in single serum samples from 110 women with prospective normal pregnancies of between 7 and 14 weeks' gestation. The level of pregnancy specific #betta# 1 glycoprotein (SP 1 ) was also measured in these samples and normal ranges for PAPP-P and SP 1 were constructed from the results obtained. (author)

  15. Maternal serum lipid levels in pregnant women with gestational diabetes mellitus (GDM in comparison to normal pregnant women

    Directory of Open Access Journals (Sweden)

    soheila Akbari

    2013-02-01

    Conclusion: Due to positive correlation of hypertriglyceridemia and hyperinsulinemia, it is possible to assume that elevated TGs levels in GDM cases is a reflection of variation in maternal insulin levels.

  16. Studies on level of cytokines and expression of connexin43 in tumor and normal cells in culture conditions

    International Nuclear Information System (INIS)

    Asati, V.; Pandey, B.N.

    2016-01-01

    Factors secreted from the tumor cells in culture medium have been known to facilitate the growth of fresh cultures and also to affect the cellular radio-sensitivity. Moreover, expression of gap junction proteins like connexin-43 is known as a key player in cell survival and proliferation. The present study is aimed to evaluate the effects of conditioned medium on the growth of respective tumor/normal cells and the expression of connexin-43 in these cells

  17. Initiation of glucose-lowering treatment decreases international normalized ratio levels among users of vitamin K antagonists

    DEFF Research Database (Denmark)

    Stage, Tore Bjerregaard; Pottegård, Anton; Henriksen, Daniel Pilsgaard

    2016-01-01

    -lowering treatment affects international normalized ratio (INR) and dose requirements of the anticoagulant VKAs warfarin and phenprocoumon. PATIENTS/METHODS: We performed a self-controlled retrospective register-based study. A total of 118 patients initiating glucose-lowering treatment while being treated......-lowering treatment reduces the anticoagulant effect of VKA to an extent that is likely to be clinically relevant. This finding needs confirmation and mechanistic explanation. This article is protected by copyright. All rights reserved....

  18. Vitamin D levels in patients with albinism compared with those in normally pigmented Black patients attending dermatology clinics in the Free State province, South Africa.

    Science.gov (United States)

    Van der Walt, Johanna E C; Sinclair, Werner

    2016-09-01

    Associations between vitamin D deficiency and a broad variety of independent diseases, including several bone diseases, various types of cancer, autoimmune diseases, hypertension, and cardiovascular disease, have been suggested. It is therefore important to detect and treat vitamin D deficiency in high-risk groups. Because patients with albinism (PWA) practice a policy of strict sun avoidance, they may be at risk for low levels of vitamin D. This study was conducted in patients attending dermatology clinics in the Free State, South Africa, to determine sun avoidance behavior in the patient population and to compare 25-hydroxyvitamin D (25[OH]D) levels in PWA with those in normally pigmented Black patients attending the same clinics. Serum 25(OH)D levels were assessed in 50 PWA and 50 normally pigmented Black control subjects. Questionnaires on sun exposure avoidance behaviors were administered to all participants. The present study showed no statistically significant difference in median 25(OH)D levels between PWA and controls with normally pigmented Black skin. Rather, the study found a tendency for controls to have lower 25(OH)D levels. A total of 53% (n = 53) of all study participants (PWA and controls) had a 25(OH)D level of albinism attending dermatology clinics in the Free State, South Africa, need not be viewed as specifically at risk for low vitamin D levels. © 2015 The International Society of Dermatology.

  19. Fasting plasma glucose and serum uric acid levels in a general Chinese population with normal glucose tolerance: A U-shaped curve.

    Directory of Open Access Journals (Sweden)

    Yunyang Wang

    Full Text Available Although several epidemiological studies assessed the relationship between fasting plasma glucose (FPG and serum uric acid (SUA levels, the results were inconsistent. A cross-sectional study was conducted to investigate this relationship in Chinese individuals with normal glucose tolerance.A total of 5,726 women and 5,457 men with normal glucose tolerance were enrolled in the study. All subjects underwent a 75-g oral glucose tolerance test. Generalized additive models and two-piecewise linear regression models were applied to assess the relationship.A U-shaped relationship between FPG and SUA was observed. After adjusting for potential confounders, the inflection points of FPG levels in the curves were 4.6 mmol/L in women and 4.7 mmol/L in men respectively. SUA levels decreased with increasing fasting plasma glucose concentrations before the inflection points (regression coefficient [β] = -36.4, P < 0.001 for women; β = -33.5, P < 0.001 for men, then SUA levels increased (β = 17.8, P < 0.001 for women; β = 13.9, P < 0.001 for men. Additionally, serum insulin levels were positively associated with FPG and SUA (P < 0.05.A U-shaped relationship between FPG and SUA levels existed in Chinese individuals with normal glucose tolerance. The association is partly mediated through serum insulin levels.

  20. High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients

    Directory of Open Access Journals (Sweden)

    Kanda Eiichiro

    2013-01-01

    Full Text Available Abstract Background Metabolic acidosis leads to chronic kidney disease (CKD progression. The guidelines recommend a lower limit of serum bicarbonate level, but no upper limit. For serum bicarbonate level to be clinically useful as a therapeutic target marker, it is necessary to investigate the target serum bicarbonate level within the normal range to prevent CKD progression. Methods One hundred and thirteen elderly CKD patients, whose serum bicarbonate level was controlled within the normal range, were enrolled in this retrospective cohort study in Ibaraki, Japan. Outcome was defined as a decrease of 25% or more in estimated glomerular filtration rate (eGFR or starting dialysis. We used Cox proportional hazard models adjusted for patients’ characteristics to examine the association between serum bicarbonate level and the outcome. Results Female patients were 36.3%: average age (SD, 70.4 (6.6 years; eGFR, 25.7 (13.6 ml/min/1.73 m2; serum bicarbonate level, 27.4 (3.2 mEq/l. Patients with the lowest quartile of serum bicarbonate levels [23.4 (1.8 mEq/l] showed a high risk of CKD progression compared with patients with high serum bicarbonate levels [28.8 (2.3 mEq/l]: adjusted hazard ratio (HR, 3.511 (95% CI, 1.342-9.186. A 1 mEq/l increase in serum bicarbonate level was associated with a low risk of CKD progression: adjusted HR, 0.791 [95% confidence interval (CI, 0.684-0.914]. Conclusions In elderly CKD patients, our findings suggest that serum bicarbonate level is independently associated with CKD progression, and that a high serum bicarbonate level is associated with a low risk of CKD progression. A high target serum bicarbonate level within the normal range may be effective for preventing CKD progression.

  1. Assessment of Microcirculatory Hemoglobin Levels in Normal and Diabetic Subjects using Diffuse Reflectance Spectroscopy in the Visible Region — a Pilot Study

    Science.gov (United States)

    Sujatha, N.; Anand, B. S. Suresh; Nivetha, K. Bala; Narayanamurthy, V. B.; Seshadri, V.; Poddar, R.

    2015-07-01

    Light-based diagnostic techniques provide a minimally invasive way for selective biomarker estimation when tissues transform from a normal to a malignant state. Spectroscopic techniques based on diffuse reflectance characterize the changes in tissue hemoglobin/oxygenation levels during the tissue transformation process. Recent clinical investigations have shown that changes in tissue oxygenation and microcirculation are observed in diabetic subjects in the initial and progressive stages. In this pilot study, we discuss the potential of diffuse reflectance spectroscopy (DRS) in the visible (Vis) range to differentiate the skin microcirculatory hemoglobin levels between normal and advanced diabetic subjects with and without neuropathy. Average concentration of hemoglobin as well as hemoglobin oxygen saturation within the probed tissue volume is estimated for a total of four different sites in the foot sole. The results indicate a statistically significant decrease in average total hemoglobin and increase in hemoglobin oxygen saturation levels for diabetic foot compared with a normal foot. The present study demonstrates the ability of reflectance spectroscopy in the Vis range to determine and differentiate the changes in tissue hemoglobin and hemoglobin oxygen saturation levels in normal and diabetic subjects.

  2. Background levels of heavy metals in surficial sediments of the Gulf of Lions (NW Mediterranean): An approach based on 133Cs normalization and lead isotope measurements

    International Nuclear Information System (INIS)

    Roussiez, Vincent; Ludwig, Wolfgang; Probst, Jean-Luc; Monaco, Andre

    2005-01-01

    This paper presents an attempt to reach natural background levels of heavy metals in surficial sediments of the Gulf of Lions (NW Mediterranean). To correct for the grain-size effect, normalization procedures based on a clay mineral indicator element are commonly used, after a first grain size separation by sieving. In our study, we tested the applicability of this method with respect to commonly used normalizer elements, and found that stable Cs shows the best ability to reflect the fine sediment fraction. Background levels were successfully reached for Co, Cr, Cu, Ni and Pb, compared to various literature references. Nevertheless, in the case of lead, the normalized data depicted a general enrichment in all samples, and the natural levels could only be reached when concentrations were corrected for the atmospheric contribution by analysing lead isotope ratios. Also for Zn, a general enrichment was found in our samples, although less important. - Among several potential normalizers, stable Cs ( 133 Cs) depicted the best ability to correct for the grain-size effect of shelf sediments and was used to estimate regional background levels of heavy metals

  3. Hair removal in hirsute women with normal testosterone levels: a randomized controlled trial of long-pulsed diode laser vs. intense pulsed light

    DEFF Research Database (Denmark)

    Haak, C S; Jensen, Pernille Nymann; Pedersen, A T

    2010-01-01

    Hirsutism is a common disorder in women of reproductive age, and androgen disturbances may aggravate the condition. Limited evidence exists regarding efficacy of hair removal in this specific population and no data are available for patients with verified normal testosterone levels....

  4. High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels.

    Science.gov (United States)

    Portillo-Sanchez, Paola; Bril, Fernando; Maximos, Maryann; Lomonaco, Romina; Biernacki, Diane; Orsak, Beverly; Subbarayan, Sreevidya; Webb, Amy; Hecht, Joan; Cusi, Kenneth

    2015-06-01

    Nonalcoholic fatty liver disease (NAFLD) and its more severe form with steatohepatitis (NASH) are common in patients with type 2 diabetes mellitus (T2DM). However, they are usually believed to largely affect those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD by the gold standard, liver magnetic resonance spectroscopy ((1)H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile. We recruited 103 patients with T2DM and normal plasma aminotransferases (age, 60 ± 8 y; body mass index [BMI], 33 ± 5 kg/m(2); glycated hemoglobin [A1c], 7.6 ± 1.3%). We measured the following: 1) liver triglyceride content by (1)H-MRS; 2) systemic insulin sensitivity (homeostasis model assessment-insulin resistance); and 3) adipose tissue insulin resistance, both fasting (as the adipose tissue insulin resistance index: fasting plasma free fatty acids [FFA] × insulin) and during an oral glucose tolerance test (as the suppression of FFA). The prevalence of NAFLD and NASH were much higher than expected (50% and 56% of NAFLD patients, respectively). The prevalence of NAFLD was higher in obese compared with nonobese patients as well as with increasing BMI (P = .001 for trend). Higher plasma A1c was associated with a greater prevalence of NAFLD and worse liver triglyceride accumulation (P = .01). Compared with nonobese patients without NAFLD, patients with NAFLD had severe systemic (liver/muscle) and, particularly, adipose tissue (fasting/postprandial) insulin resistance (all P < .01). The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases. Moreover, many are at increased risk of NASH. Physicians should have a lower threshold for screening patients with T2DM for NAFLD/NASH.

  5. An Efficient Normalized Rank Based SVM for Room Level Indoor WiFi Localization with Diverse Devices

    Directory of Open Access Journals (Sweden)

    Yasmine Rezgui

    2017-01-01

    Full Text Available This paper proposes an efficient and effective WiFi fingerprinting-based indoor localization algorithm, which uses the Received Signal Strength Indicator (RSSI of WiFi signals. In practical harsh indoor environments, RSSI variation and hardware variance can significantly degrade the performance of fingerprinting-based localization methods. To address the problem of hardware variance and signal fluctuation in WiFi fingerprinting-based localization, we propose a novel normalized rank based Support Vector Machine classifier (NR-SVM. Moving from RSSI value based analysis to the normalized rank transformation based analysis, the principal features are prioritized and the dimensionalities of signature vectors are taken into account. The proposed method has been tested using sixteen different devices in a shopping mall with 88 shops. The experimental results demonstrate its robustness with no less than 98.75% correct estimation in 93.75% of the tested cases and 100% correct rate in 56.25% of cases. In the experiments, the new method shows better performance over the KNN, Naïve Bayes, Random Forest, and Neural Network algorithms. Furthermore, we have compared the proposed approach with three popular calibration-free transformation based methods, including difference method (DIFF, Signal Strength Difference (SSD, and the Hyperbolic Location Fingerprinting (HLF based SVM. The results show that the NR-SVM outperforms these popular methods.

  6. Predictors of Cord Blood Leptin Level in Pregnancies Complicated With Preeclampsia, Fetal Growth Restriction and in Normal Pregnancies

    Directory of Open Access Journals (Sweden)

    Nilgün Öztürk Doğan

    2007-04-01

    CONCLUSION: Regulation of cord blood leptin level is a complex process involving fetal gender and fetal anthropometric variables as well as cord blood cortisol, intrauterine growth and hypoxia. Leptin level is decreased in cases of placental insufficiency like IUGR but not in uncomplicated preeclampsia alone.

  7. Associations between apolipoprotein E genotypes and serum levels of glucose, cholesterol, and triglycerides in a cognitively normal aging Han Chinese population.

    Science.gov (United States)

    Tao, Qing-Qing; Chen, Yan; Liu, Zhi-Jun; Sun, Yi-Min; Yang, Ping; Lu, Shen-Ji; Xu, Miao; Dong, Qin-Yun; Yang, Jia-Jun; Wu, Zhi-Ying

    2014-01-01

    To determine the associations between apolipoprotein E (APOE) genotypes and serum levels of glucose, total cholesterol, and triglycerides in a cognitively normal aging Han Chinese population. There were 1,003 cognitively normal aging subjects included in this study. APOE genotypes were analyzed and biochemical parameters were tested. All the subjects were divided into three groups according to APOE genotypes: (1) E2/2 or E2/3 (APOE E2); (2) E3/3 (APOE E3); and (3) E2/4, E3/4, or E4/4 (APOE E4). Correlations of serum levels of glucose, total cholesterol, and triglycerides with APOE genotypes were assessed. E2, E3, and E4 allele frequencies were found to be 6.2%, 82.1%, and 11.7%, respectively. Serum levels of total cholesterol were higher in the APOE E4 group (Ptriglycerides (adjusted odds ratio 1.042, 95% confidence interval 0.759-1.429, P=0.800). A higher serum level of total cholesterol was significantly correlated with APOE E4 status in a cognitively normal, nondiabetic aging population. However, there was no correlation between APOE genotypes and serum levels of glucose or total triglycerides.

  8. Synthetic osteogenic extracellular matrix formed by coated silicon dioxide nanosprings

    Directory of Open Access Journals (Sweden)

    Hass Jamie L

    2012-01-01

    Full Text Available Abstract Background The design of biomimetic materials that parallel the morphology and biology of extracellular matrixes is key to the ability to grow functional tissues in vitro and to enhance the integration of biomaterial implants into existing tissues in vivo. Special attention has been put into mimicking the nanostructures of the extracellular matrix of bone, as there is a need to find biomaterials that can enhance the bonding between orthopedic devices and this tissue. Methods We have tested the ability of normal human osteoblasts to propagate and differentiate on silicon dioxide nanosprings, which can be easily grown on practically any surface. In addition, we tested different metals and metal alloys as coats for the nanosprings in tissue culture experiments with bone cells. Results Normal human osteoblasts grown on coated nanosprings exhibited an enhanced rate of propagation, differentiation into bone forming cells and mineralization. While osteoblasts did not attach effectively to bare nanowires grown on glass, these cells propagated successfully on nanosprings coated with titanium oxide and gold. We observed a 270 fold increase in the division rate of osteoblasts when grow on titanium/gold coated nanosprings. This effect was shown to be dependent on the nanosprings, as the coating by themselves did not alter the growth rate of osteoblast. We also observed that titanium/zinc/gold coated nanosprings increased the levels of osteoblast production of alkaline phosphatase seven folds. This result indicates that osteoblasts grown on this metal alloy coated nanosprings are differentiating to mature bone making cells. Consistent with this hypothesis, we showed that osteoblasts grown on the same metal alloy coated nanosprings have an enhanced ability to deposit calcium salt. Conclusion We have established that metal/metal alloy coated silicon dioxide nanosprings can be used as a biomimetic material paralleling the morphology and biology of

  9. Proposal for a new normalization reference in LCA based on “safe operating space”: presentation of framework and global factors at midpoint level

    DEFF Research Database (Denmark)

    Bjørn, Anders; Hauschild, Michael Zwicky

    Planetary boundaries have been suggested for a range of environmental impacts,such as climate change, eutrophying nutrients and land use. The boundaries demarcate the safe operating space of humanity: Staying within the space ensures environmental sustainability, while exceeding it risks pushing...... ecosystems into alternative regimes, leading to adverse effects for humanity. Planetary boundaries can be applied as policy targets. To promote a societal development in the direction of these targets, an indicator system is needed that measures the fraction of the safe operating space that a given activity...... normalization factors in units compatible with characterized results at midpoint level in LCA. Our suggested framework allows expressing normalized results in units of “sustainable person years”. Normalization factors are derived by dividing the safe operating space by the global population. The proposed...

  10. Analysis of extracellular polymeric substances (EPS) and ciprofloxacin-degrading microbial community in the combined Fe-C micro-electrolysis-UBAF process for the elimination of high-level ciprofloxacin.

    Science.gov (United States)

    Zhang, Longlong; Yue, Qinyan; Yang, Kunlun; Zhao, Pin; Gao, Baoyu

    2018-02-01

    Extracellular polymeric substances (EPS) and ciprofloxacin-degrading microbial community in the combined Fe-C micro-electrolysis and up-flow biological aerated filter (UBAF) process for the treatment of high-level ciprofloxacin (CIP) were analyzed. The research demonstrated a great potential of Fe-C micro-electrolysis-UBAF for the elimination of high-level CIP. Above 90% of CIP removal was achieved through the combined process at 100 mg L -1 of CIP loading. In UBAF, the pollutants were mainly removed at 0-70 cm heights. Three-dimensional fluorescence spectrum (3D-EEM) was used to characterize the chemical structural of loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) extracted from biofilm sample in UBAF. The results showed that the protein-like substances in LB-EPS and TB-EPS had no clear change in the study. Nevertheless, an obvious release of polysaccharides in EPSs was observed during long-term exposure to CIP, which was considered as a protective response of microbial to CIP toxic. The high-throughput sequencing results revealed that the biodiversity of bacteria community became increasingly rich with gradual ciprofloxacin biodegradation in UBAF. The ciprofloxacin-degrading microbial community was mainly dominated by Proteobacteria and Bacteroidetes. Microorganisms from genera Dechloromonas, Brevundimonas, Flavobacterium, Sphingopyxis and Bosea might take a major role in ciprofloxacin degradation. This study provides deep theoretical guidance for real CIP wastewater treatment. Copyright © 2017. Published by Elsevier Ltd.

  11. An assessment of racial differences in the upper limits of normal ALT levels in children and the effect of obesity on elevated values.

    Science.gov (United States)

    Kliethermes, S; Ma, M; Purtell, C; Balasubramanian, N; Gonzalez, B; Layden, T J; Cotler, S J

    2017-10-01

    Childhood obesity is a risk factor for non-alcoholic fatty liver disease and poses important public health issues for children. Racial differences in alanine aminotransferase (ALT) levels among children have not been described. This study aimed to identify racial differences in upper limit normal (ULN) ALT levels and evaluate the effect of obesity on elevated levels in children without other metabolic risk factors. National Health and Nutrition Examination Surveys and clinical data from the Loyola University Health System were used to determine ULN ALT by race and gender. Quantile regression was used to evaluate the impact of obesity on elevated ALT and to identify potential risk factors for ALT above the ULN. Upper limit normal (ULN) ALT was approximately 28.0 and 21.0-24.0 U/L for boys and girls, respectively. No significant difference in ULN ALT across race was observed. Obesity was significantly associated with elevated ALT; obese children with elevated ALT had values 10 U/L higher than normal-weight children. Racial differences in ALT levels among adults are not evident in children. Obesity, in the absence of metabolic risk factors and other causes of liver disease, is associated with elevated ALT, providing evidence against the concept of healthy obesity in children. © 2016 World Obesity Federation.

  12. [Adiponectin levels in breast milk of overweight/obese and normal weight mothers in the metropolitan area of Monterrey, México].

    Science.gov (United States)

    Galindo Gómez, Abelardo; Flores Scheufler, Pamela; Quevedo Escobar, Yamile; González Magaña, Regina; Rodríguez De Ita, Julieta

    Given the current epidemic of childhood obesity, it has become increasingly important to understand the risks and protective factors associated with this disease. Breastfeeding has been identified as a protective factor; however, the mechanism responsible has not been elucidated. One of the current theories analyzes the role of hormones in breast milk, with special emphasis on adiponectin. This study aims to compare adiponectin levels in breast milk of mothers with normal weight with those in breast milk of overweight/obese mothers as well as to correlate these levels with the infant's weight gain. Forty samples of breast milk were analyzed for adiponectin levels using ELISA, 20 from mothers with normal weight and 20 from overweight/obese mothers. Adiponectin levels were lower in breast milk obtained from overweight/obese mothers than in breast milk from mothers with normal weight (p Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  13. Relationship between elevated triglyceride levels with the increase of HOMA-IR and HOMA-β in healthy children and adolescents with normal weight.

    Science.gov (United States)

    Simental-Mendía, Luis E; Castañeda-Chacón, Argelia; Rodriguez-Morán, Martha; Aradillas-García, Celia; Guerrero-Romero, Fernando

    2015-05-01

    To test the hypothesis that mildly elevated triglyceride levels are associated with the increase of homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-β) indices in healthy children and adolescents with normal weight, we conducted a cross-sectional population study. Based on fasting triglyceride levels, participants were allocated into groups with and without triglyceride levels ≥1.2 mmol/L. Normal weight was defined by body mass index between the 15th and 85th percentiles, for age and gender. Insulin resistance and insulin secretion were estimated using HOMA-IR and HOMA-β indices. A total of 1660 children and adolescents were enrolled, of them 327 (19.7%) with mildly elevated triglycerides. The multivariate linear regression analysis showed that mildly elevated triglyceride levels in children were associated with HOMA-IR (β = 0.214, p HOMA-β (β = 0.139, p = 0.001), systolic (β = 0.094, p = 0.01), and diastolic blood pressure (β = 0.102, p = 0.007), whereas in adolescents, HOMA-IR (β = 0.267, p HOMA-β (β = 0.154, p HOMA-IR and HOMA-β indices in healthy children and adolescents with normal weight.

  14. Characteristics of Febrile Patients with Normal White Blood Cell Counts and High C-Reactive Protein Levels in an Emergency Department

    Directory of Open Access Journals (Sweden)

    Kuan-Ting Liu

    2008-05-01

    Full Text Available Fever is one of the more common chief complaints of patients who visit emergency departments (ED. Many febrile patients have markedly elevated C-reactive protein (CRP levels and normal white blood cell (WBC counts. Most of these patients have bacterial infection and no previous underlying disease of impaired WBC functioning. We reviewed patients who visited our ED between November 2003 and July 2004. The WBC count and CRP level of patients over 18 years of age who visited the ED because of or with fever were recorded. Patients who had normal WBC count (4,000–10,000/mL and high CRP level (> 100 mg/L were included. The data, including gender, age and length of hospital stay, were reviewed. Underlying diseases, diagnosis of the febrile disease and final condition were recorded according to the chart. Within the study period, 54,078 patients visited our ED. Of 5,628 febrile adults, 214 (3.8% had elevated CRP level and normal WBC count. The major cause of febrility was infection (82.24%. Most of these patients were admitted (92.99%. There were 32 patients with malignant neoplasm, nine with liver cirrhosis, 66 with diabetes mellitus and 11 with uremia. There were no significant differences in age and gender between patients with and those without neoplasm. However, a higher inhospital mortality rate and other causes of febrility were noted in patients with neoplasm. It was not rare in febrile patients who visited the ED to have a high CRP level but normal WBC count. These patients did not necessarily have an underlying malignant neoplasm or hematologic illness. Factors other than malignant neoplasm or hematologic illness may be associated with the WBC response, and CRP may be a better indicator of infection under such conditions.

  15. Distribution pattern of urine albumin creatinine ratio and the prevalence of high-normal levels in untreated asymptomatic non-diabetic hypertensive patients.

    Science.gov (United States)

    Ohmaru, Natsuki; Nakatsu, Takaaki; Izumi, Reishi; Mashima, Keiichi; Toki, Misako; Kobayashi, Asako; Ogawa, Hiroko; Hirohata, Satoshi; Ikeda, Satoru; Kusachi, Shozo

    2011-01-01

    Even high-normal albuminuria is reportedly associated with cardiovascular events. We determined the urine albumin creatinine ratio (UACR) in spot urine samples and analyzed the UACR distribution and the prevalence of high-normal levels. The UACR was determined using immunoturbidimetry in 332 untreated asymptomatic non-diabetic Japanese patients with hypertension and in 69 control subjects. The microalbuminuria and macroalbuminuria levels were defined as a UCAR ≥30 and creatinine and a UCAR ≥300 µg/mg·creatinine, respectively. The distribution patterns showed a highly skewed distribution for the lower levels, and a common logarithmic transformation produced a close fit to a Gaussian distribution with median, 25th and 75th percentile values of 22.6, 13.5 and 48.2 µg/mg·creatinine, respectively. When a high-normal UACR was set at >20 to creatinine, 19.9% (66/332) of the hypertensive patients exhibited a high-normal UACR. Microalbuminuria and macroalbuminuria were observed in 36.1% (120/336) and 2.1% (7/332) of the patients, respectively. UACR was significantly correlated with the systolic and diastolic blood pressures and the pulse pressure. A stepwise multivariate analysis revealed that these pressures as well as age were independent factors that increased UACR. The UACR distribution exhibited a highly skewed pattern, with approximately 60% of untreated, non-diabetic hypertensive patients exhibiting a high-normal or larger UACR. Both hypertension and age are independent risk factors that increase the UACR. The present study indicated that a considerable percentage of patients require anti-hypertensive drugs with antiproteinuric effects at the start of treatment.

  16. Plasma C3d levels of young farmers correlate with respirable dust exposure levels during normal work in swine confinement buildings

    DEFF Research Database (Denmark)

    Hoffmann, Hans Jürgen; Iversen, Martin; Brandslund, Ivan

    2003-01-01

    Work in swine confinement buildings leads to an inflammatory response and may be associated with increased levels of acute phase proteins. We compared the inflammatory response of a control group of young former farm workers with age-matched former farm workers who had previously developed the lo...... in response to respiratory dust, more so amongst cases than in the control group. Acute exposure, with work related levels of organic dust containing endotoxin, leads to a weak systemic inflammatory response....

  17. Deficits in audiovisual speech perception in normal aging emerge at the level of whole-word recognition.

    Science.gov (United States)

    Stevenson, Ryan A; Nelms, Caitlin E; Baum, Sarah H; Zurkovsky, Lilia; Barense, Morgan D; Newhouse, Paul A; Wallace, Mark T

    2015-01-01

    Over the next 2 decades, a dramatic shift in the demographics of society will take place, with a rapid growth in the population of older adults. One of the most common complaints with healthy aging is a decreased ability to successfully perceive speech, particularly in noisy environments. In such noisy environments, the presence of visual speech cues (i.e., lip movements) provide striking benefits for speech perception and comprehension, but previous research suggests that older adults gain less from such audiovisual integration than their younger peers. To determine at what processing level these behavioral differences arise in healthy-aging populations, we administered a speech-in-noise task to younger and older adults. We compared the perceptual benefits of having speech information available in both the auditory and visual modalities and examined both phoneme and whole-word recognition across varying levels of signal-to-noise ratio. For whole-word recognition, older adults relative to younger adults showed greater multisensory gains at intermediate SNRs but reduced benefit at low SNRs. By contrast, at the phoneme level both younger and older adults showed approximately equivalent increases in multisensory gain as signal-to-noise ratio decreased. Collectively, the results provide important insights into both the similarities and differences in how older and younger adults integrate auditory and visual speech cues in noisy environments and help explain some of the conflicting findings in previous studies of multisensory speech perception in healthy aging. These novel findings suggest that audiovisual processing is intact at more elementary levels of speech perception in healthy-aging populations and that deficits begin to emerge only at the more complex word-recognition level of speech signals. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Low levels of Survival Motor Neuron protein are sufficient for normal muscle function in the SMNΔ7 mouse model of SMA.

    Science.gov (United States)

    Iyer, Chitra C; McGovern, Vicki L; Murray, Jason D; Gombash, Sara E; Zaworski, Phillip G; Foust, Kevin D; Janssen, Paul M L; Burghes, Arthur H M

    2015-11-01

    Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder characterized by loss of lower motor neurons. SMA is caused by deletion or mutation of the Survival Motor Neuron 1 (SMN1) gene and retention of the SMN2 gene. The loss of SMN1 results in reduced levels of the SMN protein. SMN levels appear to be particularly important in motor neurons; however SMN levels above that produced by two copies of SMN2 have been suggested to be important in muscle. Studying the spatial requirement of SMN is important in both understanding how SMN deficiency causes SMA and in the development of effective therapies. Using Myf5-Cre, a muscle-specific Cre driver, and the Cre-loxP recombination system, we deleted mouse Smn in the muscle of mice with SMN2 and SMNΔ7 transgenes in the background, thus providing low level of SMN in the muscle. As a reciprocal experiment, we restored normal levels of SMN in the muscle with low SMN levels in all other tissues. We observed that decreasing SMN in the muscle has no phenotypic effect. This was corroborated by muscle physiology studies with twitch force, tetanic and eccentric contraction all being normal. In addition, electrocardiogram and muscle fiber size distribution were also normal. Replacement of Smn in muscle did not rescue SMA mice. Thus the muscle does not appear to require high levels of SMN above what is produced by two copies of SMN2 (and SMNΔ7). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Extracellular signaling and multicellularity in Bacillus subtilis.

    Science.gov (United States)

    Shank, Elizabeth Anne; Kolter, Roberto

    2011-12-01

    Bacillus subtilis regulates its ability to differentiate into distinct, co-existing cell types in response to extracellular signaling molecules produced either by itself, or present in its environment. The production of molecules by B. subtilis cells, as well as their response to these signals, is not uniform across the population. There is specificity and heterogeneity both within genetically identical populations as well as at the strain-level and species-level. This review will discuss how extracellular signaling compounds influence B. subtilis multicellularity with regard to matrix-producing cannibal differentiation, germination, and swarming behavior, as well as the specificity of the quorum-sensing peptides ComX and CSF. It will also highlight how imaging mass spectrometry can aid in identifying signaling compounds and contribute to our understanding of the functional relationship between such compounds and multicellular behavior. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Effects of endurance and high intensity training on ICAM-1 and VCAM-1 levels and arterial pressure in obese and normal weight adolescents.

    Science.gov (United States)

    Kargarfard, Mehdi; Lam, Eddie T C; Shariat, Ardalan; Asle Mohammadi, Mahmoud; Afrasiabi, Saleh; Shaw, Ina; Shaw, Brandon S

    2016-09-01

    Obesity prevalence has increased in Iranian adolescents in recent years. However, few studies have examined the impact of intervention programs on this health issue. The main objective of this study was to evaluate the effects of 8-week endurance training (ET) and high intensity interval training (HIIT) on intercellular adhesion molecule-1(ICAM-1) and vascular adhesion molecule-1(VCAM-1) levels among obese and normal-weight male adolescents. Thirty obese and 30 normal-weight subjects were assigned to the ET, HIIT, or control group for eight weeks. Before and after the intervention, ICAM-1, VCAM-1, body weight, BMI, VO2max, and blood pressures were measured. SPSS (Version 21) was used for data analysis, and the significance level was set at p HIIT (from 517 ± 72 ng/ml to 374 ± 50 ng/ml), but their VCAM-1 level was significantly (p HIIT (from 1689 ± 119 ng/ml to 1282 ± 63 ng/ml). Similarly, normal weight participants significantly (p HIIT (from 289 ± 22 ng/ml to 202 ± 12 ng/ml), but their VCAM-1 level was significantly (p HIIT (from 895 ± 50 ng/ml to 673 ± 142 ng/ml). Systolic blood pressure and diastolic blood pressures of all the participants were significantly (p HIIT. While both the ET and HIIT were useful in lowering the SBP and DBP of the participants, HIIT was more effective than ET in reducing ICAM-1 and VCAM-1 content in normal and obese adolescents.

  1. High glucose enhances cAMP level and extracellular signal-regulated kinase phosphorylation in Chinese hamster ovary cell: Usage of Br-cAMP in foreign protein β-galactosidase expression.

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    Lin, Hsiao-Hsien; Lee, Tsung-Yih; Liu, Ting-Wei; Tseng, Ching-Ping

    2017-07-01

    Glucose is a carbon source for Chinese hamster ovary (CHO) cell growth, while low growth rate is considered to enhance the production of recombinant proteins. The present study reveals that glucose concentrations higher than 1 g/L reduce the growth rate and substantially increase in cAMP (∼300%) at a high glucose concentration (10 g/L). High glucose also enhances the phosphorylation of extracellular signal-regulated kinase (ERK) and p27 kip by Western blot analysis. To determine whether the phosphorylation of ERK is involved in the mechanism, a cyclic-AMP dependent protein kinase A (PKA) inhibitor (H-8) or MEK (MAPKK) inhibitor (PD98059) was added to block ERK phosphorylation. We show that both the high glucose-induced ERK phosphorylation and growth rate return to baseline levels. These results suggest that the cAMP/PKA and MAP signaling pathways are involved in the abovementioned mechanism. Interestingly, the direct addition of 8-bromo-cAMP (Br-cAMP), a membrane-permeable cAMP analog, can mimic the similar effects produced by high glucose. Subsequently Br-cAMP could induce β-galactosidase (β-Gal) recombinant protein expression by 1.6-fold. Furthermore, Br-cAMP can additionally enhance the β-Gal production (from 2.8- to 4.5-fold) when CHO cells were stimulated with glycerol, thymidine, dimethyl sulfoxide, pentanoic acid, or sodium butyrate. Thus, Br-cAMP may be used as an alternative agent in promoting foreign protein expression for CHO cells. Copyright © 2017. Published by Elsevier B.V.

  2. Comparison of serum levels of Tri‐iodothyronine (T3, Thyroxine (T4, and Thyroid‐Stimulating Hormone (TSH in preeclampsia and normal pregnancy

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    Nayereh Khadem

    2012-01-01

    Full Text Available Background: The physiological changes in thyroid gland during pregnancy have been suggested as one of the pathophysiologic causes of preeclampsia.Objective: The aim of this study was comparison of serum levels of Tri‐iodothyronine (T3, Thyroxine (T4, and Thyroid‐Stimulating Hormone (TSH in preeclampsia and normal pregnancy. Materials and Methods: In this case‐control study, 40 normal pregnant women and 40 cases of preeclampsia in third trimester of pregnancy were evaluated. They were compared for serum levels of Free T3 (FT3, Free T4 (FT4 and TSH. The data was analyzed by SPSS software with the use of t‐student, Chi‐square, Independent sample T-test and Bivariate correlation test. p≤0.05 was considered statistically significant. Results: The mean age was not statistically different between two groups (p=0.297. No significant difference was observed in terms of parity between two groups (p=0.206. Normal pregnant women were not significantly different from preeclampsia cases in the view of FT3 level (1.38 pg/ml vs. 1.41 pg/ml, p=0.803, FT4 level (0.95 pg/ml vs. 0.96 pg/ml, p=0.834 and TSH level (3.51 μIU/ml vs. 3.10 μIU/ml, p=0.386. Conclusion: The findings of the present study do not support the hypothesis that changes in FT3, FT4 and TSH levels could be possible etiology of preeclampsia

  3. Second-trimester IL-15 and IL-18 levels in the amniotic fluid of fetuses with normal karyotypes and with chromosome abnormalities.

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    Klimkiewicz-Blok, Dominika; Florjański, Jerzy; Zalewski, Jerzy; Blok, Radosław

    2012-01-01

    Little is known about the behavior of interleukin 15 (IL-15) and 18 (IL-18) in the amniotic fluid in the second trimester of gestations complicated by chromosomal defects in the fetus. Likewise, it has not yet been established whether a fetus with chromosome abnormalities creates its immunity mechanisms in the same way as a fetus with a normal karyotype. The aim of this work was to assess the concentration of IL-15 and IL-18 in the amniotic fluid in the second trimester of gestation in fetuses with normal karyotypes and with chromosome abnormalities. The material consisted of 51 samples of amniotic fluid obtained from genetic amniocenteses carried out between the 15th and the 19th weeks of gestation. On the basis of cytogenetic screening, two groups were singled out: Group I--45 fetuses with normal karyotypes, and Group II--6 fetuses with abnormal karyotypes. The concentrations of IL-15 and IL-18 in the amniotic fluid were assessed with ready-made assays and analyzed, and the results from both groups were compared. The differences between the IL-15 levels in the amniotic fluid from Groups I and II proved to be statistically insignificant (p = 0.054). However, the average IL-18 levels in the amniotic fluid of the fetuses with normal karyotypes were significantly higher than in the amniotic fluid of the fetuses with chromosome abnormalities (p = 0.032). Some defense mechanisms in the second trimester of gestation in fetuses with chromosome abnormalities may develop in a different way than in fetuses with normal karyotypes.

  4. Early intraoperative blood collection does not affect complete blood counts, von Willebrand factor or factor VIII levels in normal children.

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    Darwish, Hanni; Mundell, Gillianne; Engen, Dale; Lillicrap, David; Silva, Mariana; James, Paula

    2011-01-01

    Obtaining blood from children for research studies can be difficult, particularly for controls. One solution is to obtain samples during elective surgery; however, consideration must be given to the potential effects of the timing of phlebotomy. Ten children were recruited and phlebotomy was carried out during a preoperative clinic visit and intraoperatively immediately after the induction of anesthesia but before the start of surgery. CBCs, VWF, and FVIII levels were measured at both time points and no significant differences were seen. This negative result may be beneficial to pediatric research by suggesting that early intraoperative blood collection for controls does not affect the results.

  5. Comparison of the Blood Level OF Leptin in Umbilical Cord of Newborns of Mothers With Gestational Diabetes and Normal Mothers and Its Relationship With Growth Indices of Newborns

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    Aramesh

    2015-09-01

    Full Text Available Background Diabetes is defined as an abnormal increase in blood glucose levels and is the most common disease that can complicate pregnancy. Leptin, a hormone produced mainly in adipose tissue, plays an important role in preventing fat accumulation in tissues such as skeletal muscle and myocardium and can be used to evaluate changes in lipid levels effectively. Leptin cannot cross the placental barrier, and its level in the umbilical cord is of fetal origin. Objectives Due to the lack of similar studies in Ahvaz, we aimed to determine the relationship between umbilical blood levels of this hormone with growth indices of newborns with normal mothers and mothers with gestational diabetes mellitus (GDM. Materials and Methods After delivery and using the aseptic method, 5 mL of blood from the umbilical vein was taken immediately by staffs to separate serum and was then stored at −20°C. Serum level of leptin was measured using the Elisa method in two groups: “case” and “control.” All information collected in the questionnaires was analyzed using SPSS-19 software as well as other statistical methods. Results Serum leptin levels in the cord blood of mothers with GDM were significantly higher than in normal mothers. There was a significant relationship between serum leptin levels and birth weight in infants with diabetic mothers. In this study, no significant correlation was observed between cord leptin levels and other growth indices. Conclusions Changes in neonatal leptin levels can reflect changes in the body fat tissue and neonatal birth weight and could be effective in predicting weight gain in newborns with mothers who have gestational diabetes and may reduce birth trauma or future complications.

  6. High-level inducible Smad4-reexpression in the cervical cancer cell line C4-II is associated with a gene expression profile that predicts a preferential role of Smad4 in extracellular matrix composition

    International Nuclear Information System (INIS)

    Klein-Scory, Susanne; Zapatka, Marc; Eilert-Micus, Christina; Hoppe, Sabine; Schwarz, Elisabeth; Schmiegel, Wolff; Hahn, Stephan A; Schwarte-Waldhoff, Irmgard

    2007-01-01

    Smad4 is a tumour suppressor frequently inactivated in pancreatic and colorectal cancers. We have recently reported loss of Smad4 in every fourth carcinoma of the uterine cervix. Smad4 transmits signals from the TGF-β superfamily of cytokines and functions as a versatile transcriptional co-modulator. The prevailing view suggests that the tumour suppressor function of Smad4 primarily resides in its capability to mediate TGF-β growth inhibitory responses. However, accumulating evidence indicates, that the acquisition of TGF-β resistance and loss of Smad4 may be independent events in the carcinogenic process. Through inducible reexpression of Smad4 in cervical cancer cells we wished to shed more light on this issue and to identify target genes implicated in Smad4 dependent tumor suppression. Smad4-deficient human C4-II cervical carcinoma cells were used to establish inducible Smad4 reexpression using the commercial Tet-on™ system (Clontech). The impact of Smad4 reexpression on cell growth was analysed in vitro and in vivo. Transcriptional responses were assessed through profiling on cDNA macroarrays (Clontech) and validated through Northern blotting. Clones were obtained that express Smad4 at widely varying levels from approximately physiological to 50-fold overexpression. Smad4-mediated tumour suppression in vivo was apparent at physiological expression levels as well as in Smad4 overexpressing clones. Smad4 reexpression in a dose-dependent manner was associated with transcriptional induction of the extracellular matrix-associated genes, BigH3, fibronectin and PAI-1, in response to TGF-β. Smad4-dependent regulation of these secreted Smad4 targets is not restricted to cervical carcinoma cells and was confirmed in pancreatic carcinoma cells reexpressing Smad4 after retroviral transduction and in a stable Smad4 knockdown model. On the other hand, the classical cell cycle-associated TGF-β target genes, c-myc, p21 and p15, remained unaltered. Our results show that

  7. Fructose containing sugars do not raise blood pressure or uric acid at normal levels of human consumption.

    Science.gov (United States)

    Angelopoulos, Theodore J; Lowndes, Joshua; Sinnett, Stephanie; Rippe, James M

    2015-02-01

    The impact of fructose, commonly consumed with sugars by humans, on blood pressure and uric acid has yet to be defined. A total of 267 weight-stable participants drank sugar-sweetened milk every day for 10 weeks as part of their usual, mixed-nutrient diet. Groups 1 and 2 had 9% estimated caloric intake from fructose or glucose, respectively, added to milk. Groups 3 and 4 had 18% of estimated caloric intake from high fructose corn syrup or sucrose, respectively, added to the milk. Blood pressure and uric acid were determined prior to and after the 10-week intervention. There was no effect of sugar type on either blood pressure or uric acid (interaction P>.05), and a significant time effect for blood pressure was noted (Pfructose at the 50th percentile level, whether consumed as pure fructose or with fructose-glucose-containing sugars, does not promote hyperuricemia or increase blood pressure. © 2014 Wiley Periodicals, Inc.

  8. Maternal serum alpha-fetoprotein levels are normal in Fanconi anemia: Can it be a lack of postnatal inhibition of AFP gene resulting in the elevation?

    Science.gov (United States)

    Aslan, Deniz; Karabacak, Recep Onur; Aslan, Oner Deniz

    2017-04-01

    We investigated the feasibility of using serum alpha-fetoprotein (AFP) levels as a screening test for prenatal diagnosis of Fanconi anemia (FA). Serial measurements in maternal serum were recorded. Parents, both heterozygous for FA, had declined prenatal molecular testing. The infant was born with no somatic abnormalities, and FA was confirmed by postnatal molecular analysis. Maternal serum AFP levels during each trimester of pregnancy were normal indicating that these levels cannot be used as a screening test in prenatal diagnosis. Three-year follow-up after birth showed constantly elevated serum levels in the patient from the start, suggesting a lack of postnatal inhibition on AFP gene. © 2016 Wiley Periodicals, Inc.

  9. A Low-Normal Free Triiodothyronine Level Is Associated with Adverse Prognosis in Euthyroid Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

    Science.gov (United States)

    Chen, Yu-Yang; Shu, Xiao-Rong; Su, Zi-Zhuo; Lin, Rong-Jie; Zhang, Hai-Feng; Yuan, Wo-Liang; Wang, Jing-Feng; Xie, Shuang-Lun

    2017-12-12

    Thyroid dysfunction is prevalent in patients with heart failure (HF) and hypothyroidism is related to the adverse prognosis of HF subjects receiving cardiac resynchronization therapy (CRT). We aim to investigate whether low-normal free triiodothyronine (fT3) level is related to CRT response and the prognosis of euthyroid patients with HF after CRT implantation.One hundred and thirteen euthyroid patients who received CRT therapy without previous thyroid disease and any treatment affecting thyroid hormones were enrolled. All of patients were evaluated for cardiac function and thyroid hormones (serum levels of fT3, free thyroxine [fT4] and thyroid-stimulating hormone [TSH]). The end points were overall mortality and hospitalization for HF worsening. During a follow-up period of 39 ± 3 weeks, 36 patients (31.9%) died and 45 patients (39.8%) had hospitalization for HF exacerbation. A higher rate of NYHA III/IV class and a lower fT3 level were both observed in death group and HF event group. Multivariate Cox regression analyses disclosed that a lower-normal fT3 level (HR = 0.648, P = 0.009) and CRT response (HR = 0.441, P = 0.001) were both independent predictors of overall mortality. In addition, they were also both related to HF re-hospitalization event (P < 0.01 for both). Patients with fT3 < 3.00 pmol/L had a significantly higher overall mortality than those with fT3 ≥ 3.00 pmol/L (P = 0.027). Meanwhile, a higher HF hospitalization event rate was also found in patients with fT3 < 3.00 pmol/L (P < 0.001).A lower-normal fT3 level is correlated with a worse cardiac function an adverse prognosis in euthyroid patients with HF after CRT implantation.

  10. IGF-1 levels across the spectrum of normal to elevated in acromegaly: relationship to insulin sensitivity, markers of cardiovascular risk and body composition.

    Science.gov (United States)

    Reid, Tirissa J; Jin, Zhezhen; Shen, Wei; Reyes-Vidal, Carlos M; Fernandez, Jean Carlos; Bruce, Jeffrey N; Kostadinov, Jane; Post, Kalmon D; Freda, Pamela U

    2015-12-01

    Activity of acromegaly is gauged by levels of GH and IGF-1 and epidemiological studies demonstrate that their normalization reduces acromegaly's excess mortality rate. However, few data are available linking IGF-1 levels to features of the disease that may relate to cardiovascular (CV) risk. Therefore, we tested the hypothesis that serum IGF-1 levels relative to the upper normal limit relate to insulin sensitivity, serum CV risk markers and body composition in acromegaly. In this prospective, cross-sectional study conducted at a pituitary tumor referral center we studied 138 adult acromegaly patients, newly diagnosed and previously treated surgically, with fasting and post-oral glucose levels of endocrine and CV risk markers and body composition assessed by DXA. Active acromegaly is associated with lower insulin sensitivity, body fat and CRP levels than acromegaly in remission. %ULN IGF-1 strongly predicts insulin sensitivity, better than GH and this persists after adjustment for body fat and lean tissue mass. %ULN IGF-1 also relates inversely to CRP levels and fat mass, positively to lean tissue and skeletal muscle estimated (SM(E)) by DXA, but not to blood pressure, lipids, BMI or waist circumference. Gender interacts with the IGF-1-lean tissue mass relationship. Active acromegaly presents a unique combination of features associated with CV risk, reduced insulin sensitivity yet lower body fat and lower levels of some serum CV risk markers, a pattern that is reversed in remission. %ULN IGF-1 levels strongly predict these features. Given the known increased CV risk of active acromegaly, these findings suggest that of these factors insulin resistance is most strongly related to disease activity and potentially to the increased CV risk of active acromegaly.

  11. Serum bilirubin and antioxidant levels in first degree relatives of patients with ischemic heart disease and normal subjects

    International Nuclear Information System (INIS)

    Mahmood, N.; Naseem, T.; Mukhtar, F.; Basheer, R.

    2011-01-01

    Background: Coronary diseases appear to result from an overbalance between radical-generating, compared with radical-scavenging systems, a condition called as oxidative stress. Total antioxidant status (TAS) in human plasma reflects the balance between oxidants and antioxidants in each system. Bilirubin has been considered an antioxidant, with capacity to remove reactive species of oxygen. Present study tried to measure the total antioxidant status of first degree relatives of patients with IHD. Study also tried to evaluate the prognostic role of serum bilirubin in disease prevention or progression. Methods: Seventy five apparently healthy subjects in age group 20-50 years, comprising equal number of males and females, who were first degree relatives of ischemic heart disease patients, were included in the study. Family members were divided on the bases of their numbers, i.e., one family member (Group-A), 2 family members (Group-B) and more than 3 family members (Group-C). Study was cross sectional and carried out in a period of 6 months (Jun 2008-Jan 2009). Subjects with letter of consent were taken from general population. Seventy five healthy age matched people with no history of ischemic heart disease in family were taken as control. An overnight fasting blood sample was taken. Total antioxidant status was determined using a commercially available kit. Serum bilirubin was estimated by auto analyzer. Results: Family history of ischemic heart disease with serum bilirubin showed a significant negative correlation (p<0.05). But the values of TAS failed to show any significant correlation with the family history. It was observed that the value of serum bilirubin was decreased significantly (p<0.05) with an increased number of family members. Total antioxidant status failed to show any significant difference among all the three groups. Conclusion: Our data demonstrated that reduced serum levels of bilirubin were seen in people with a higher prevalence of coronary

  12. Beyond the Normalized Difference Vegetation Index (NDVI): Developing a Natural Space Index for population-level health research.

    Science.gov (United States)

    Rugel, Emily J; Henderson, Sarah B; Carpiano, Richard M; Brauer, Michael

    2017-11-01

    Natural spaces can provide psychological benefits to individuals, but population-level epidemiologic studies have produced conflicting results. Refining current exposure-assessment methods is necessary to advance our understanding of population health and to guide the design of health-promoting urban forms. The aim of this study was to develop a comprehensive Natural Space Index that robustly models potential exposure based on the presence, form, accessibility, and quality of multiple forms of greenspace (e.g., parks and street trees) and bluespace (e.g., oceans and lakes). The index was developed for greater Vancouver, Canada. Greenness presence was derived from remote sensing (NDVI/EVI); forms were extracted from municipal and private databases; and accessibility was based on restrictions such as private ownership. Quality appraisals were conducted for 200 randomly sampled parks using the Public Open Space Desktop Appraisal Tool (POSDAT). Integrating these measures in GIS, exposure was assessed for 60,242 postal codes using 100- to 1,600-m buffers based on hypothesized pathways to mental health. A single index was then derived using principal component analysis (PCA). Comparing NDVI with alternate approaches for assessing natural space resulted in widely divergent results, with quintile rankings shifting for 22-88% of postal codes, depending on the measure. Overall park quality was fairly low (mean of 15 on a scale of 0-45), with no significant difference seen by neighborhood-level household income. The final PCA identified three main sets of variables, with the first two components explaining 68% of the total variance. The first component was dominated by the percentages of public and private greenspace and bluespace and public greenspace within 250m, while the second component was driven by lack of access to bluespace within 1 km. Many current approaches to modeling natural space may misclassify exposures and have limited specificity. The Natural Space Index

  13. Design of the Demineralized Water Make-up Line to Maintain the Normal Pool Water Level of the Reactor Pool in the Research Reactor

    International Nuclear Information System (INIS)

    Yoon, Hyun Gi; Choi, Jung Woon; Yoon, Ju Hyeon; Chi, Dae Young

    2012-01-01

    In many research reactors, hot water layer system (HWLS) is used to minimize the pool top radiation level. Reactor pool divided into the hot water layer at the upper part of pool and the cold part below the hot water layer with lower temperature during normal operation. Water mixing between these layers is minimized because the hot water layer is formed above cold water. Therefore the hot water layer suppresses floatation of cold water and reduces the pool top radiation level. Pool water is evaporated form the surface to the building hall because of high temperature of the hot water layer; consequently the pool level is continuously fallen. Therefore, make-up water is necessary to maintain the normal pool level. There are two way to supply demineralized water to the pool, continuous and intermittent methods. In this system design, the continuous water make-up method is adopted to minimize the disturbance of the reactor pool flow. Also, demineralized water make-up is connected to the suction line of the hot water layer system to raise the temperature of make-up water. In conclusion, make-up demineralized water with high temperature is continuously supplied to the hot water layer in the pool

  14. Activation of retinal glial (Müller cells by extracellular ATP induces pronounced increases in extracellular H+ flux.

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    Boriana K Tchernookova

    Full Text Available Small alterations in extracellular acidity are potentially important modulators of neuronal signaling within the vertebrate retina. Here we report a novel extracellular acidification mechanism mediated by glial cells in the retina. Using self-referencing H+-selective microelectrodes to measure extracellular H+ fluxes, we show that activation of retinal Müller (glial cells of the tiger salamander by micromolar concentrations of extracellular ATP induces a pronounced extracellular H+ flux independent of bicarbonate transport. ADP, UTP and the non-hydrolyzable analog ATPγs at micromolar concentrations were also potent stimulators of extracellular H+ fluxes, but adenosine was not. The extracellular H+ fluxes induced by ATP were mimicked by the P2Y1 agonist MRS 2365 and were significantly reduced by the P2 receptor blockers suramin and PPADS, suggesting activation of P2Y receptors. Bath-applied ATP induced an intracellular rise in calcium in Müller cells; both the calcium rise and the extracellular H+ fluxes were significantly attenuated when calcium re-loading into the endoplasmic reticulum was inhibited by thapsigargin and when the PLC-IP3 signaling pathway was disrupted with 2-APB and U73122. The anion transport inhibitor DIDS also markedly reduced the ATP-induced increase in H+ flux while SITS had no effect. ATP-induced H+ fluxes were also observed from Müller cells isolated from human, rat, monkey, skate and lamprey retinae, suggesting a highly evolutionarily conserved mechanism of potential general importance. Extracellular ATP also induced significant increases in extracellular H+ flux at the level of both the outer and inner plexiform layers in retinal slices of tiger salamander which was significantly reduced by suramin and PPADS. We suggest that the novel H+ flux mediated by ATP-activation of Müller cells and of other glia as well may be a key mechanism modulating neuronal signaling in the vertebrate retina and throughout the brain.

  15. Aerobic bacterial microbiota of the conjunctiva in diabetic patients with normal and altered glycated hemoglobin levels in two regions in Brazil

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    Natalia Pimentel Moreno

    2014-12-01

    Full Text Available Purpose: To study the aerobic bacterial microbiota of the conjunctiva in diabetic patients with regard to the management of diabetes, assessed using glycated hemoglobin levels. Methods: A cross-sectional study was conducted using conjunctival smears of diabetic patients from both sexes and with different ages, residing in two different Brazilian cities (Sorocaba and Rio Branco. A control group of non-diabetic patients was also included. The diabetic patients were considered to have controlled diabetes when their glycated hemoglobin level was ≤7% and blood glucose level was ≤126 mg/dL. Patients with non-controlled diabetes were those with glycated hemoglobin levels >7% and blood glucose levels >126 mg/dL. The samples obtained were inoculated in Brain-Heart Infusion broth and in culture media for aerobic bacteria (blood and chocolate agars; bacterial growth was evaluated in a microbiology laboratory. Results: A total of 120 eyes of 120 patients were included in the present study. The percentage of cultures in which bacterial growth was observed was greater in diabetic patients, although the difference was not statistically significant (p=0.103. There was a greater trend toward bacterial growth in the conjunctiva of diabetic patients with altered fasting blood glucose. There was no difference in the frequency of bacterial growth on the conjunctiva between diabetic patients with normal or altered glycated hemoglobin levels. In Sorocaba, conjunctival bacterial growth was similar to that observed in Rio Branco. The microorganism most frequently detected in the present study was Staphylococcus epidermidis, followed by Staphylococcus aureus, Proteus mirabilis, and Escherichia coli. Conclusion: There was no difference between diabetic patients with normal or altered glycated hemoglobin levels. The microorganisms found were similar to those found in studies investigating the conjunctival bacterial flora of diabetic and non-diabetic patients.

  16. Cushing`s disease: Fibrinogen and D-dimer levels fail to normalize despite early postoperative remission - a prospective, controlled study.

    Science.gov (United States)

    Witek, Przemysław; Zieliński, Grzegorz; Szamotulska, Katarzyna; Witek, Joanna; Kamiński, Grzegorz

    2016-01-01

    Effective transsphenoidal surgery (TSS) for Cushing`s disease (CD) normalizes cortisol levels and reduces complications of hypercortisolism. However, there is evidence of increased cardiovascular morbidity even after successful surgery. A prospective, controlled study on the dynamics of fibrinogen and D-dimer levels with a six-month follow-up after an effective TSS for CD. Forty patients with CD and forty healthy age- and sex-matched subjects were included. We assessed ACTH, urinary and serum cortisol, and fibrinogen and D-dimer levels before TSS and during follow-up. Baseline BMI (P < 0.001), fibrinogen (P = 0.002), and D-dimer (P = 0.001) levels in CD patients were significantly higher than those in healthy controls. High fibrinogen levels in the CD group were independent of BMI, and were positively associated with hsCRP (rS = 0.61, P < 0.001) and arterial hypertension (P = 0.029). After the six-month follow-up we confirmed a sustained difference between the remission group and controls in fibrinogen and D-dimer levels (P = 0.001 and P = 0.017, respectively). Despite early biochemical remission of CD the levels of fibrinogen and D-dimer failed to decrease. This probably contributes to the high risk of thrombotic events and indicates the need for a close follow-up for signs of thromboembolic and cardiovascular complications in patients with early CD remission. (Endokrynol Pol 2016; 67 (3): 283-291).

  17. Insertion of tetracysteine motifs into dopamine transporter extracellular domains.

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    Deanna M Navaroli

    Full Text Available The neuronal dopamine transporter (DAT is a major determinant of extracellular dopamine (DA levels and is the primary target for a variety of addictive and therapeutic psychoactive drugs. DAT is acutely regulated by protein kinase C (PKC activation and amphetamine exposure, both of which modulate DAT surface expression by endocytic trafficking. In order to use live imaging approaches to study DAT endocytosis, methods are needed to exclusively label the DAT surface pool. The use of membrane impermeant, sulfonated biarsenic dyes holds potential as one such approach, and requires introduction of an extracellular tetracysteine motif (tetraCys; CCPGCC to facilitate dye binding. In the current study, we took advantage of intrinsic proline-glycine (Pro-Gly dipeptides encoded in predicted DAT extracellular domains to introduce tetraCys motifs into DAT extracellular loops 2, 3, and 4. [(3H]DA uptake studies, surface biotinylation and fluorescence microscopy in PC12 cells indicate that tetraCys insertion into the DAT second extracellular loop results in a functional transporter that maintains PKC-mediated downregulation. Introduction of tetraCys into extracellular loops 3 and 4 yielded DATs with severely compromised function that failed to mature and traffic to the cell surface. This is the first demonstration of successful introduction of a tetracysteine motif into a DAT extracellular domain, and may hold promise for use of biarsenic dyes in live DAT imaging studies.

  18. Normal results of post-race thallium-201 myocardial perfusion imaging in marathon runners with elevated serum MB creatine kinase levels

    International Nuclear Information System (INIS)

    Siegel, A.J.; Silverman, L.M.; Holman, B.L.

    1985-01-01

    Elevated cardiac enzyme values in asymptomatic marathon runners after competition can arise from skeletal muscle through exertional rhabdomyolysis, silent injury to the myocardium, or a combined tissue source. Peak post-race levels of the MB isoenzyme of creatine kinase are similar to values in patients with acute myocardial infarction. Previously reported normal results of infarct-avid myocardial scintigraphy with technetium 99m pyrophosphate in runners after competition suggest a non-cardiac source but cannot exclude silent injury to the myocardium. Therefore, thallium 201 myocardial perfusion imaging was performed in runners immediately after competition together with determination of sequential cardiac enzyme levels. Among 15 runners tested, the average peak in serum MB creatine kinase 24 hours after the race was 128 IU/liter with a cumulative MB creatine kinase release of 117 IU/liter; these values are comparable to those in patients with acute transmural myocardial infarction. Thallium 201 myocardial scintigraphic results were normal in five runners randomly selected from those who volunteered for determination of sequential blood levels. It is concluded that elevations of serum MB creatine kinase in marathon runners arise from a skeletal muscle source and that thallium 201 myocardial scintigraphy is useful to assess runners for myocardial injury when clinical questions arise

  19. Independent predictive factors for significant liver histological changes in patients with HBeAg-positive high-viral-load chronic HBV infection and a normal alanine aminotransferase level

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    LI Qiang

    2016-07-01

    Full Text Available Objective To investigate the independent predictive factors for significant liver histological changes (SLHCs in patients with HBeAg-positive high-viral-load chronic hepatitis B virus (HBV infection and a normal alanine aminotransferase (ALT level. MethodsA retrospective analysis was performed on the clinical data of 116 previously untreated patients with HBeAg-positive high-viral-load (HBV DNA≥105 copies/ml chronic HBV infection and a normal ALT level (<50 U/L who were hospitalized in Shanghai Public Health Clinical Center Affiliated to Fudan University from June 2013 to August 2015. The definition of SLHCs was inflammation ≥G2 and/or fibrosis≥S2. The t-test or Mann-Whitney U rank sum test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate regression analyses were used to determine independent predictive factors for SLHCs. ResultsOf all the 116 patients, 47(40.5% had SLHCs. The multivariate analysis showed that age (OR=2.828, P<0.05, ALT (OR=1.011, P<0.05, and gamma-glutamyl transpeptidase (GGT (OR=1.089, P<0.05 were independent predictors for SLHCs in patients with HBeAg-positive high-viral-load chronic HBV infection and a normal ALT level. The patients aged ≤30 years had a significantly lower incidence rate of SLHCs than those aged>30 years (21.6% vs 49.4%, χ2=6.42, P=0.015, the patients with ALT ≤30 U/L had a significantly lower incidence rate of SLHCs than those with 30 U/L<ALT≤50 U/L (17.6% vs 50.0%, χ2=19.86, P<0.001, and the patients with GGT≤40 U/L had a significantly lower incidence rate of SLHCs than those with GGT>40 U/L (28.8% vs 66.7%, χ2=28.63, P<0.001. ConclusionIn patients with HBeAg-positive high-viral-load chronic HBV infection and a normal ALT level, those with an age of>30 years, ALT>30 U/L, and GGT>40 U/L tend to develop SLHCs and need liver biopsy.

  20. A model for the analysis of a normal evolution scenarios for a deep geological granite repository for high-level radioactive waste

    International Nuclear Information System (INIS)

    Cormenzana Lopez, J.L.; Cunado, M.A.; Lopez, M.T.

    1996-01-01

    The methodology usually used to evaluate the behaviour of deep geological repositories for high-level radioactive wastes comprises three phases: Identification of factors (processes, characteristics and events) that can affect the repository. Generation of scenarios. In general, a normal evolution scenario (Reference Scenario) and various disruptive scenarios (earthquake, human intrusion, etc) are considered. Evaluation of the behaviour of the repository in each scenario. The normal evolution scenario taking into account all factors with a high probability of occurrence is the first to be analysed. The performance assessment of behaviour being carried out by ENRESA for the AGP Granite has led to the identification of 63 of these factors. To analyse repository behaviour in the normal evolution scenario, it is necessary to first of all create an integrated model of the global system. This is a qualitative model including the 63 factors identified. For a global view of a such a complex system, it is very useful to graphically display the relationship between factors in an Influence Diagram. This paper shows the Influence Diagram used in the analysis of the AGP Granite Reference Scenario. (Author)

  1. Sex ratio at birth: scenario from normal- and high-level natural radiation areas of Kerala coast in south-west India

    International Nuclear Information System (INIS)

    Koya, P.K.M.; Jaikrishan, G.; Sudheer, K.R.; Madhusoodhanan, M.; Jagadeesan, C.K.; Das, Birajalaxmi; Andrews, V.J.

    2015-01-01

    Newborns were monitored for congenital malformations in four government hospitals located in high-level (ambient dose >1.5 mGy/year) and normal-level (≤1.5 mGy/year) natural radiation areas of Kerala, India, from August 1995 to December 2012. Sex ratio at birth (SRB) among live singleton newborns and among previous children, if any, of their mothers without history of any abortion, stillbirth or twins is reported here. In the absence of environmental stress or selective abortion of females, global average of SRB is about 1050 males to 1000 females. A total of 151,478 singleton, 1031 twins, 12 triplets and 1 quadruplet deliveries were monitored during the study period. Sex ratio among live singleton newborns was 1046 males (95 % CI 1036-1057) for 1000 females (77,153 males:73,730 females) and was comparable to the global average. It was similar in high-level and normal-level radiation areas of Kerala with SRB of 1050 and 1041, respectively. It was consistently more than 1000 and had no association with background radiation levels, maternal and paternal age at birth, parental age difference, gravida status, ethnicity, consanguinity or year of birth. Analysis of SRB of the children of 139,556 women whose reproductive histories were available suggested that couples having male child were likely to opt for more children and this, together with enhanced rate of males at all birth order, was skewing the overall SRB in favour of male children. Though preference for male child was apparent, extreme steps of sex-selective abortion or infanticide were not prevalent. (orig.)

  2. 13N-ammonia rest/stress PET. Folic acid improves global coronary vasoreactivity in coronary artery disease patients with normal or elevated homocysteine levels

    International Nuclear Information System (INIS)

    Graf, S.; Nikfardjam, M.; Khorsand, A.; Maurer, G.; Ofluoglu, S.; Dudczak, R.; Kletter, K.; Nekolla, S.; Huber, K.; Pirich, C.

    2006-01-01

    Aim: hyperhomocysteinaemia (Hhcy) is known to be an independent risk factor for vascular disease. Coronary flow reserve (CFR) measured by positron emission tomography (PET) is a sensitive method to monitor the effects of pharmacologic interventions in Hhcy. We assessed coronary vascular reactivity by PET in patients with coronary artery disease (CAD) dependent on their homocysteine (Hcy) levels before and under high dose folic acid supplementation therapy (FAST). Patients, methods: twelve patients with CAD underwent rest/adenosine 13 N-ammonia PET for quantification of myocardial blood flow (MBF) and CFR before and after nine weeks FAST (10 mg/day). Results: folate levels increased from 21 ± 6 to 210 ± 34 μg/l (+900%, p < 0.0001) while Hcy levels decreased from 12.1 ± 3.6 to 9.1 ± 3.1 μmol/l (-25%; p < 0.01). Global resting MBF remained nearly unchanged after FAST, while stress MBF (from 2.61 ± 0.93 to 3.25 ± 1.15 ml/g/min; p = 0.05) and CFR (from 3.00 ± 0.76 to 3.72 ± 0.93 ml/g/min; p < 0.05; +24%) significantly increased in patients with normal and elevated Hcy levels (cut off 12 μmol/l). An inverse relation was found between Hcy and CFR (R = -0.53; p = 0.08) and between Hcy and MBF at rest (R = -0.62; p < 0.05) at baseline conditions, not persisting after FAST. Conclusion: coronary vascular reactivity con be improved by FAST in patients with CAD and normal or elevated Hcy levels. FAST might lower an increased cardiovascular risk in CAD patients possibly by mechanisms that are not related to Hcy. (orig.)

  3. Sex ratio at birth: scenario from normal- and high-level natural radiation areas of Kerala coast in south-west India

    Energy Technology Data Exchange (ETDEWEB)

    Koya, P.K.M.; Jaikrishan, G.; Sudheer, K.R. [Bhabha Atomic Research Centre, Low Level Radiation Research Laboratory, Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Kollam (India); Madhusoodhanan, M. [Victoria Hospital, Department of Paediatrics, Kollam (India); Jagadeesan, C.K. [Directorate of Health Services, Thiruvananthapuram (India); Das, Birajalaxmi [Bhabha Atomic Research Centre, Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Mumbai (India); Andrews, V.J.

    2015-11-15

    Newborns were monitored for congenital malformations in four government hospitals located in high-level (ambient dose >1.5 mGy/year) and normal-level (≤1.5 mGy/year) natural radiation areas of Kerala, India, from August 1995 to December 2012. Sex ratio at birth (SRB) among live singleton newborns and among previous children, if any, of their mothers without history of any abortion, stillbirth or twins is reported here. In the absence of environmental stress or selective abortion of females, global average of SRB is about 1050 males to 1000 females. A total of 151,478 singleton, 1031 twins, 12 triplets and 1 quadruplet deliveries were monitored during the study period. Sex ratio among live singleton newborns was 1046 males (95 % CI 1036-1057) for 1000 females (77,153 males:73,730 females) and was comparable to the global average. It was similar in high-level and normal-level radiation areas of Kerala with SRB of 1050 and 1041, respectively. It was consistently more than 1000 and had no association with background radiation levels, maternal and paternal age at birth, parental age difference, gravida status, ethnicity, consanguinity or year of birth. Analysis of SRB of the children of 139,556 women whose reproductive histories were available suggested that couples having male child were likely to opt for more children and this, together with enhanced rate of males at all birth order, was skewing the overall SRB in favour of male children. Though preference for male child was apparent, extreme steps of sex-selective abortion or infanticide were not prevalent. (orig.)

  4. COMPARISON OF STRESS LEVELS IN THE PARENTS OF CHILDREN WITH CEREBRAL PALSY AND PARENTS OF NORMAL CHILDREN IN VADODARA REGION OF GUJARAT

    Directory of Open Access Journals (Sweden)

    Dr. Vivek H. Ramanandi

    2015-04-01

    Full Text Available Background: Parenting is inherently stressful at times and several studies have shown that being a caregiver of a child who is disabled is even more stressful. A number of studies have identified the factors which exacerbate or mediate parenting stress in caregivers of children who are disabled. The aim of this study was to assess the parenting stress levels in parents of children who have cerebral palsy as compared to parents of normal children. Further objectives were to ascertain variables predictive of parenting stress levels. Methods: The Gujarati translated version of Parenting Stress Index/Short Form was first validated and was given to 49 parents of children with cerebral palsy (Group-A who were attending Varun Mahajan Apang Shishu Mandal, Vadodara and to the 50 parents of normal children(Group-B. Caregivers also completed a demographic questionnaire. 43 questionnaires from Group-A and 45 from Group-B were returned to the researcher. Means and frequencies were used to summarise the demographic data. T-tests were performed to establish whether there was any significant difference between the parenting stress levels in Group-A and Group-B. Results: The parents in Group-A showed clinically significant, and in many cases, pathological levels of parenting stress as compared to the parents in Group-B. Conclusions: The results of this study confirm that parenting stress is complex matter and it is important to predict the parenting stress levels of caregivers of disabled children. Therapists should evaluate the needs of each family individually and follow a family centred approach when managing children with cerebral palsy.

  5. Normal values in ambulatory oesophageal pH monitoring at two levels in Spain Valores normales en pHmetría esofágica ambulatoria a dos niveles en España

    Directory of Open Access Journals (Sweden)

    2010-07-01

    Full Text Available Aim: upper oesophageal pH monitoring may play a significant role in the study of extra-oesophageal GERD, but limited normal data are available to date. Our aim was to develop a large series of normal values of proximal oesophageal acidification. Methods: 155 healthy volunteers (74 male participated in a multi-centre national study including oesophageal manometry and 24 hours oesophageal pH monitoring using two electrodes individually located 5 cm above the LOS and 3 cm below the UOS. Results: 130 participants with normal manometry completed all the study. Twelve of them were excluded for inadequate pH tests. Twenty-seven subjects had abnormal conventional pH. The remaining 91 subjects (37 M; 18-72 yrs age range formed the reference group for normality. At the level of the upper oesophagus, the 95th percentile of the total number of reflux events was 30, after eliminating the meal periods 22, and after eliminating also the pseudo-reflux events 18. Duration of the longest episodes was 5, 4 and 4 min, respectively (3.5 min in upright and 0.5 min in supine. The upper limit for the percentage of acid exposure time was 1.35, 1.05 and 0.95%, respectively. No reflux events were recorded in the upper oesophagus in 8 cases. Conclusion: this is the largest series of normal values of proximal oesophageal reflux that confirm the existence of acid reflux at that level in healthy subjects, in small quantity and unrelated to age or gender. Our data support the convenience of excluding pseudo-reflux events and meal periods from analysis.Objetivo: la pHmetría con electrodo proximal puede jugar un papel importante en el estudio de las manifestaciones extraesofágicas de la ERGE, pero no existen series amplias que permitan establecer los valores de referencia con fiabilidad. Métodos: se incluyeron 155 voluntarios sanos (74 H en un estudio multicéntrico a nivel nacional con manometría esofágica y pHmetría de 24 horas con dos electrodos individuales a 5 cm por

  6. Acute high-intensity interval exercise induces comparable levels of circulating cell-free DNA and Interleukin-6 in obese and normal-weight individuals.

    Science.gov (United States)

    Ferrandi, Peter J; Fico, Brandon G; Whitehurst, Michael; Zourdos, Michael C; Bao, Fanchen; Dodge, Katelyn M; Rodriguez, Alexandra L; Pena, Gabriel; Huang, Chun-Jung

    2018-06-01

    Obesity is associated with lipid aggregation in adipocytes and macrophage infiltration, leading to increased oxidative stress and inflammation. Increased cell-free DNA (cfDNA) concentrations have been observed in clinical conditions of systemic inflammation. While the beneficial effects of regular physical activity on the release of circulating cfDNA still remain unknown, acute intense exercise has been shown to increase inflammatory cytokines and cfDNA concentrations in normal-weight individuals. Therefore, the primary purpose of this study was to examine the effect of acute high-intensity interval Exercise (HIIE) on plasma cfDNA and interleukin-6 (IL-6) responses in obese and normal-weight subjects. Fourteen male subjects (7 obese and 7 normal-weight) participated in an acute HIIE protocol (30 min, 4x4min @ 80% - 90% of VO 2max ) on a treadmill. Between HIIE intervals, subjects performed 3 min of active recovery at 50-60% VO 2max . Blood samples were collected prior to, immediately following exercise, and one hour into recovery for measurements of plasma cfDNA and IL-6. Our results demonstrated a significant elevation in plasma cfDNA immediately following acute HIIE in both obese and normal-weight subjects. A comparable elevation in the concentration of plasma IL-6 was also found between two groups in response to acute HIIE. Furthermore, the level of plasma cfDNA was not correlated with IL-6 either at baseline or in response to acute HIIE. These findings may support the utilization of HIIE as a time-efficient exercise protocol to understand the obesity-associated cfDNA and inflammatory responses. Published by Elsevier Inc.

  7. Maternal circulating levels of activin A, inhibin A, sFlt-1 and endoglin at parturition in normal pregnancy and pre-eclampsia.

    Directory of Open Access Journals (Sweden)

    Aparna Reddy

    Full Text Available Maternal circulating levels of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1, endoglin (sEng and placental proteins like activin A and inhibin A are increased before the onset of pre-eclampsia. There is evidence for oxidative stress in pre eclampsia. Recently it was shown that placental oxygen concentration is related to sFlt-1 and inhibin A. In addition it is reported that oxidative stress markers are increased in placental tissue delivered after labour. Therefore, the objective of this study is to investigate if these proteins are altered in maternal circulation of labouring pre-eclampsia and normal pregnancies.To assess the effects of labour, samples were taken from 10 normal pregnant (NP and 10 pre-eclamptic (PE women pre-labour, full dilation, placental delivery and 24 h. To assess the effects of placental delivery, plasma samples were taken from 10NP and 10PE women undergoing elective Caesarean section, pre-delivery, placental delivery and 10 min, 60 min and 24 h post delivery. SFlt-1 and sEng and activin A and inhibin A were measured using commercial and in house ELISA's respectively.The levels of sFlt-1 and sEng were significantly higher in PE compared to NP women in both groups. In labour, sFlt-1 levels increased significantly at full dilatation in PE women, before declining by 24 hr. However there was no significant rise in sEng levels in labour. Activin A and inhibin A levels declined rapidly with placental delivery in NP and PE pregnancies. There was a significant rise in activin A levels during labour in PE compared to pre labour, but inhibin levels did not increase.Labour in pre-eclamptic women increases the levels of sFlt-1 and activin A. This pilot data suggests that increase in the maternal levels of these factors in labour could predict and/or contribute to the maternal syndrome postpartum.

  8. Autocrine signal transmission with extracellular ligand degradation

    International Nuclear Information System (INIS)

    Muratov, C B; Posta, F; Shvartsman, S Y

    2009-01-01

    Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand–receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers

  9. EXTRACELLULAR VESICLES: CLASSIFICATION, FUNCTIONS AND CLINICAL RELEVANCE

    Directory of Open Access Journals (Sweden)

    A. V. Oberemko

    2014-12-01

    Full Text Available This review presents a generalized definition of vesicles as bilayer extracellular organelles of all celular forms of life: not only eu-, but also prokaryotic. The structure and composition of extracellular vesicles, history of research, nomenclature, their impact on life processes in health and disease are discussed. Moreover, vesicles may be useful as clinical instruments for biomarkers, and they are promising as biotechnological drug. However, many questions in this area are still unresolved and need to be addressed in the future. The most interesting from the point of view of practical health care represents a direction to study the effect of exosomes and microvesicles in the development and progression of a particular disease, the possibility of adjusting the pathological process by means of extracellular vesicles of a particular type, acting as an active ingredient. Relevant is the further elucidation of the role and importance of exosomes to the surrounding cells, tissues and organs at the molecular level, the prospects for the use of non-cellular vesicles as biomarkers of disease.

  10. Autocrine signal transmission with extracellular ligand degradation

    Science.gov (United States)

    Muratov, C B; Posta, F; Shvartsman, S Y

    2009-03-01

    Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand-receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers.

  11. Extracellular deoxyribonuclease production by periodontal bacteria.

    Science.gov (United States)

    Palmer, L J; Chapple, I L C; Wright, H J; Roberts, A; Cooper, P R

    2012-08-01

    Whilst certain bacteria have long been known to secrete extracellular deoxyribonuclease (DNase), the purpose in microbial physiology was unclear. Recently, however, this enzyme has been demonstrated to confer enhanced virulence, enabling bacteria to evade the host's immune defence of extruded DNA/chromatin filaments, termed neutrophil extracellular traps (NETs). As NETs have recently been identified in infected periodontal tissue, the aim of this study was to screen periodontal bacteria for extracellular DNase activity. To determine whether DNase activity was membrane bound or secreted, 34 periodontal bacteria were cultured in broth and on agar plates. Pelleted bacteria and supernatants from broth cultures were analysed for their ability to degrade DNA, with relative activity levels determined using an agarose gel electrophoresis assay. Following culture on DNA-supplemented agar, expression was determined by the presence of a zone of hydrolysis and DNase activity related to colony size. Twenty-seven bacteria, including red and orange complex members Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, Parvimonas micra, Prevotella intermedia, Streptococcus constellatus, Campylobacter rectus and Prevotella nigrescens, were observed to express extracellular DNase activity. Differences in DNase activity were noted, however, when bacteria were assayed in different culture states. Analysis of the activity of secreted DNase from bacterial broth cultures confirmed their ability to degrade NETs. The present study demonstrates, for the first time, that DNase activity is a relatively common property of bacteria associated with advanced periodontal disease. Further work is required to determine the importance of this bacterial DNase activity in the pathogenesis of periodontitis. © 2011 John Wiley & Sons A/S.

  12. Clarifying Normalization

    Science.gov (United States)

    Carpenter, Donald A.

    2008-01-01

    Confusion exists among database textbooks as to the goal of normalization as well as to which normal form a designer should aspire. This article discusses such discrepancies with the intention of simplifying normalization for both teacher and student. This author's industry and classroom experiences indicate such simplification yields quicker…

  13. Plasma ceramide levels are altered in low and normal birth weight men in response to short-term high-fat overfeeding

    DEFF Research Database (Denmark)

    Ribel-Madsen, Amalie; Ribel-Madsen, Rasmus; Nielsen, Kristian Fog

    2018-01-01

    Low birth weight (LBW) individuals have an increased risk of developing insulin resistance and type 2 diabetes compared with normal birth weight (NBW) individuals. We hypothesised that LBW individuals exhibit an increased fatty acid flux into lipogenesis in non-adipose tissue with a resulting...... accumulation of lipotoxic lipids, including ceramides, in the blood. Therefore, we measured fasting plasma levels of 27 ceramides in 18 young, healthy, LBW men and 25 NBW controls after an isocaloric control diet and a 5-day high-fat, high-calorie diet by HPLC-HRMS. LBW men did not show elevated plasma......:0–18:1/d18:1–18:0 and d18:1–24:2/d18:2–24:1 levels and increased the d18:0–24:1a level in response to overfeeding. Plasma d18:0–24:1a and total ceramide levels were positively associated with the fasting blood glucose level and endogenous glucose production after the control diet, and the total ceramide...

  14. Changes in Fasting Plasma Glucose Levels with Ribavirin and Pegylated Interferon Treatment in Normal and Impaired Glucose Tolerant Patients with Chronic Hepatitis C

    Science.gov (United States)

    Sarasombath, Ongkarn; Suwantarat, Nuntra; Tice, Alan D

    2012-01-01

    Background Patients with Hepatitis C Virus (HCV) infection have increased rates of glucose intolerance, and studies have shown the improvement of fasting plasma glucose (FPG) levels after clearance of HCV infection with standard ribavirin plus pegylated interferon treatment. The purpose of this study was to examine glycemic changes with standard HCV treatment in patients with impaired fasting glucose (IFG) and normal fasting glucose (NFG). Methods A retrospective study of FPG changes in HCV patients with IFG and NFG treated with standard HCV therapy was conducted. Baseline characteristics and viral responses were assessed; FPG levels before treatment, at the end of treatment, and more than one-month post treatment were compared. Results The mean FPG levels increased by 8.68 mg/dl at the end of treatment in the NFG group but decreased by 9.0 mg/dl in the IFG group, a statistically significant difference (P=0.019). The change in FPG levels remained significantly different after adjusting for weight change (P=0.009) and weight changes and initial weight (P=0.039). FPG change from baseline at more than one month after treatment were similar in both groups (P=0.145). The change in FPG levels was not associated with sustained viral response. Conclusions In HCV-infected patients, standard ribavirin plus pegylated interferon treatment reduced FPG levels in patients with IFG and increased FPG levels in NFG individuals; independent of initial weight, weight change, or viral response. Standard HCV treatment modulates fasting plasma glucose levels which supports the need for a prospective study to determine the clinical significance of this finding. PMID:22737650

  15. High-end normal adrenocorticotropic hormone and cortisol levels are associated with specific cardiovascular risk factors in pediatric obesity: a cross-sectional study.

    Science.gov (United States)

    Prodam, Flavia; Ricotti, Roberta; Agarla, Valentina; Parlamento, Silvia; Genoni, Giulia; Balossini, Caterina; Walker, Gillian Elisabeth; Aimaretti, Gianluca; Bona, Gianni; Bellone, Simonetta

    2013-02-20

    The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been reported to be involved in obesity-associated metabolic disturbances in adults and in selected populations of adolescents. The aim of this study was to investigate the association between morning adrenocorticotropic hormone (ACTH) and cortisol levels and cardiovascular risk factors in overweight or obese Caucasian children and adolescents. This cross-sectional study of 450 obese children and adolescents (aged 4 to 18 years) was performed in a tertiary referral center. ACTH, cortisol, cardiovascular risk factors (fasting and post-challenge glucose, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, and hypertension) and insulin resistance were evaluated. All analyses were corrected for confounding factors (sex, age, puberty, body mass index), and odds ratios were determined. ACTH and cortisol levels were positively associated with systolic and diastolic blood pressure, triglycerides, fasting glucose and insulin resistance. Cortisol, but not ACTH, was also positively associated with LDL-cholesterol. When adjusted for confounding factors, an association between ACTH and 2 h post-oral glucose tolerance test glucose was revealed. After stratification according to cardiovascular risk factors and adjustment for possible confounding factors, ACTH levels were significantly higher in subjects with triglycerides ≥90th percentile (P cortisol levels were found in subjects with blood pressure ≥95th percentile and LDL-cholesterol ≥90th percentile. Overall, the highest tertiles of ACTH (>5.92 pmol/l) and cortisol (>383.5 nmol/l) although within the normal range were associated with increases in cardiovascular risk factors in this population. In obese children and adolescents, high morning ACTH and cortisol levels are associated with cardiovascular risk factors. High ACTH levels are associated with high triglyceride levels and hyperglycemia

  16. Effects of combined dietary supplementation with fenofibrate and Schisandrae Fructus pulp on lipid and glucose levels and liver function in normal and hypercholesterolemic mice

    Directory of Open Access Journals (Sweden)

    Zhu PL

    2015-02-01

    Full Text Available Pei-Li Zhu,1 Si-Yuan Pan,1 Shu-Feng Zhou,2 Yi Zhang,1 Xiao-Yan Wang,1 Nan Sun,1 Zhu-Sheng Chu,1 Zhi-Ling Yu,3 Kam-Ming Ko41Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, People’s Republic of China; 4Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, People’s Republic of ChinaBackground: Currently, combined therapy using herbs and synthetic drugs has become a feasible therapeutic intervention against some diseases. The purpose of this study was to assess the effects of supplementation with fenofibrate (FF, a chemical drug used for the treatment of hyperlipidemia, and the aqueous extract of Schisandrae Fructus (SF, a Chinese herb pulp (AqSF-P or an SF-related synthetic analog, bicyclol (BY, on serum/hepatic lipid levels and liver status in normal and hypercholesterolemic (HCL mice.Methods: Male mice obtained from the Institute of Cancer Research (ICR were fed on a normal diet (ND or high cholesterol/bile salt (0.5%/0.15%, w/w diet (HCBD containing FF (0.03% or 0.1%, w/w with or without AqSF-P (0.3%-9.0%, based on crude herbal material, w/w or BY (0.025%, w/w for 10 days. Then serum lipid levels and alanine aminotransferase (ALT activity, as well as hepatic triglyceride (TG, total cholesterol (TC, and glucose levels, were measured.Results: Oral supplementation with FF significantly reduced serum and hepatic TG, TC, and hepatic glucose levels (approximately 79% in mice fed with ND or HCBD. FF supplementation combined with AqSF-P or BY increased FF-induced reduction in hepatic TC and TG contents in ND-fed mice (up to 67% and in HCBD-fed mice (up to 54%, when compared with FF supplementation alone. Hepatic glucose-lowering effect of FF was

  17. Epidemiology of RBC Transfusions in Patients With Severe Acute Kidney Injury: Analysis From the Randomized Evaluation of Normal Versus Augmented Level Study.

    Science.gov (United States)

    Bellomo, Rinaldo; Mårtensson, Johan; Kaukonen, Kirsi-Maija; Lo, Serigne; Gallagher, Martin; Cass, Alan; Myburgh, John; Finfer, Simon

    2016-05-01

    To assess the epidemiology and outcomes associated with RBC transfusion in patients with severe acute kidney injury requiring continuous renal replacement therapy. Post hoc analysis of data from a multicenter, randomized, controlled trial. Thirty-five ICUs in Australia and New Zealand. Cohort of 1,465 patients enrolled in the Randomized Evaluation of Normal versus Augmented Level replacement therapy study. Daily information on morning hemoglobin level and amount of RBC transfused were prospectively collected in the Randomized Evaluation of Normal versus Augmented Level study. We analyzed the epidemiology of such transfusions and their association with clinical outcomes. Overall, 977 patients(66.7%) received a total of 1,192 RBC units. By day 5, 785 of 977 transfused patients (80.4%) had received at least one RBC transfusion. Hemoglobin at randomization was lower in transfused than in nontransfused patients (94 vs 111 g/L; p regression analysis, RBC transfusion was independently associated with lower 90-day mortality (hazard ratio, 0.55; 95% CI, 0.38-0.79). However, we found no independent association between RBC transfusions and mortality when the analyses were restricted to patients surviving at least 5 days (hazard ratio, 1.29; 95% CI, 0.90-1.85). We found no independent association between RBC transfusion and renal replacement therapy-free days, mechanical ventilator-free days, or length of stay in ICU or hospital. In patients with severe acute kidney injury treated with continuous renal replacement therapy, we found no association of RBC transfusion with 90-day mortality or other patient-centered outcomes. The optimal hemoglobin threshold for RBC transfusion in such patients needs to be determined in future randomized controlled trials.

  18. Differences in energy expenditure, amount of physical activity and physical exertion level during a Zumba fitness class among adult women who are normal weight, overweight and obese.

    Science.gov (United States)

    Yáñez-Sepúlveda, Rodrigo; Barraza-Gómez, Fernando; Báez-San Martin, Eduardo; Araneda, Oscar F; Zavala, Juan P; Hecht, Gernot K; Tuesta, Marcelo

    2018-01-01

    One of the most popular expressions of massive group classes of aerobic physical activity is Zumba fitness. The aim of the study was to compare and relate the energy expenditure and the amount and intensity of physical effort during a Zumba fitness class in women with different Body Mass Index (BMI). Body displacements of 61 adult women who performed a one-hour Zumba session were evaluated with triaxial accelerometers. In order to observe the effect of BMI women were divided into normal weight (N.=26), overweight (N.=21) and obese groups (N.=14). The average number of steps was 4533.3±1351 and the percentage of total class time of moderate to vigorous intensity (% MVPA) was 53.8±14.4%. The metabolic intensity average was 3.64±1.1 MET, with an energy expenditure by total body mass of 3.9±1.6 kcal/kg. When analyzing groups, the normal weight group had a greater number of steps (5184.2±1561.1 steps/class) compared to overweight (4244.8±1049.3 steps/class) and obese women (3756.9±685.7 steps/class) with Plower percentage of class time at the lower levels of intensity (sedentary and lifestyle activity levels) and more time at the highest levels (vigorous and very vigorous) compared to obese women (Plower energy expenditure values per kilo of weight (r=-0.40; Plower intensity of effort, energy expenditure and amount of physical activity during a one-hour Zumba class, restricting to overweight and obese women to achieving the effort parameters recommended to control weight and improve cardiovascular fitness.

  19. Studies on immunoproteasome in human liver. Part I: Absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis

    International Nuclear Information System (INIS)

    Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena; Mishto, Michele; Santoro, Aurelia; Fiorentino, Michelangelo; Capri, Miriam; Cescon, Matteo; Grazi, Gian Luca; Grigioni, Walter Franco; D'Errico-Grigioni, Antonia; Franceschi, Claudio

    2010-01-01

    Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive (α4 and β1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28αβ regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical data have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28αβ. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.

  20. Studies on immunoproteasome in human liver. Part I: Absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Vasuri, Francesco; Capizzi, Elisa [Pathology Unit of the ' F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy); Bellavista, Elena [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy); Mishto, Michele [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy); Institute of Biochemistry, Medical Faculty Charite, Berlin (Germany); Santoro, Aurelia [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy); Fiorentino, Michelangelo [Pathology Unit of the ' F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy); Capri, Miriam [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy); Cescon, Matteo; Grazi, Gian Luca [Unit of General and Transplantation Surgery, S.Orsola-Malpighi Hospital, Bologna University (Italy); Grigioni, Walter Franco; D' Errico-Grigioni, Antonia [Pathology Unit of the ' F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy); Franceschi, Claudio, E-mail: claudio.franceschi@unibo.it [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy)

    2010-06-25

    Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical data have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.

  1. α-Defensins Induce a Post-translational Modification of Low Density Lipoprotein (LDL) That Promotes Atherosclerosis at Normal Levels of Plasma Cholesterol.

    Science.gov (United States)

    Abu-Fanne, Rami; Maraga, Emad; Abd-Elrahman, Ihab; Hankin, Aviel; Blum, Galia; Abdeen, Suhair; Hijazi, Nuha; Cines, Douglas B; Higazi, Abd Al-Roof

    2016-02-05

    Approximately one-half of the patients who develop clinical atherosclerosis have normal or only modest elevations in plasma lipids, indicating that additional mechanisms contribute to pathogenesis. In view of increasing evidence that inflammation contributes to atherogenesis, we studied the effect of human neutrophil α-defensins on low density lipoprotein (LDL) trafficking, metabolism, vascular deposition, and atherogenesis using transgenic mice expressing human α-defensins in their polymorphonuclear leukocytes (Def(+/+)). Accelerated Def(+/+) mice developed α-defensin·LDL complexes that accelerate the clearance of LDL from the circulation accompanied by enhanced vascular deposition and retention of LDL, induction of endothelial cathepsins, increased endothelial permeability to LDL, and the development of lipid streaks in the aortic roots when fed a regular diet and at normal plasma levels of LDL. Transplantation of bone marrow from Def(+/+) to WT mice increased LDL clearance, increased vascular permeability, and increased vascular deposition of LDL, whereas transplantation of WT bone marrow to Def(+/+) mice prevented these outcomes. The same outcome was obtained by treating Def(+/+) mice with colchicine to inhibit the release of α-defensins. These studies identify a potential new link between inflammation and the development of atherosclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Development and Validation of the Persian Version of the Acceptable Noise Level (ANL Test in Normal Children Aged 5-8 Years

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    Abdollah Moossavi

    2016-06-01

    Full Text Available Background: The goal of the present study was to develop and validate the Persian version of the Acceptable Noise Level (ANL test in normal, Persianspeaking children aged 5-8 years. Methods: This tool-making and non-experimental research was conducted in two stages. In the first stage the proper story was selected and recorded after evaluation of its content validity. In the second stage this test material was administered to a total 181 normal children (97 girls and 84 boys randomly chosen from the population of preschool and primary school children of Tehran (District 5, aged 5-8 years in four age groups to evaluate the reliability of test in order to develop the Persian version of the ANL test and assess its changes during the growth. Lawshe’s method and Cronbach’s alpha coefficient were used to assess the content validity and reliability of the test, respectively. Mann– Whitney U test was used to examine gender differences, and Kruskal-Wallis test was to examine age differences. Results: Test-retest correlation of 0.74 indicated acceptable reliability of the test. Significant differences were found between most of different age groups for the ANL mean scores (P0.05. Conclusion: The study results indicated good validity and reliability of the Persian version of the ANL test in children. Therefore this test can be useful in designing classrooms suitable for 5-8 year-old children of both genders.

  3. Challenging the present definition of "normal" vitamin D levels obtained by a single blood test. Can we develop a formula to predict vitamin D levels in the 4 seasons from a single season's measure?

    Science.gov (United States)

    Tandeter, Howard

    2014-08-01

    Publications on the health effects of vitamin D (25(OH) D) had almost triplicate in the last 10years, not only for its known "calcemic effects" (calcium, phosphor, PTH), but for the more recent findings on its "non-calcemic effects" (all-cause and cardiovascular mortality, and relation with certain types of cancer). Part of these publications deal with the definition of what is a "normal" circulating level of 25(OH) D that may distinguish between health and disease. The literature also deals with seasonal variations of vitamin D, showing levels that rise in summer and fall in winter and with DBP phenotypes and geographical location that affect seasonality of 25(OH) D measurements. Despite the knowledge of the existence of these phenomena many studies on vitamin D fail to acknowledge the time of the year the blood sample was extracted. Thus, when we compare results from different studies without defining the season that the samples were drawn, we compare incomparable figures. Furthermore, it is quite absurd to define "normal levels" as a static measure (over or under a certain value) using a single blood test when the value measured is known to change with seasons. Knowing that people have different vitamin D levels in different seasons of the year, we should ask ourselves which of these measurements should be used to define a "real" or "normal" level? Is it the lower one? Is there a "mean measure" that should be used for this matter? If yes, how do we obtain it? Do we have to make 4 seasonal measurements in each patient? Alternatively, might there be a possibility of developing a formula to help us obtain the mean from a single season's measure or one season's prediction from another season's measurement? And knowing that DBP phenotypes and geographical location affect seasonality of 25(OH) D measurements; shouldn't we include this in the equation? In this article I will discuss the hypothetical existence of an Individual Mean Annual vitamin D level that I will

  4. Multi-center clinical evaluation of the Access AMH assay to determine AMH levels in reproductive age women during normal menstrual cycles.

    Science.gov (United States)

    Gracia, Clarisa R; Shin, Sanghyuk S; Prewitt, Maureen; Chamberlin, Janna S; Lofaro, Lori R; Jones, Kristin L; Clendenin, Marta; Manzanera, Katherine E; Broyles, Dennis L

    2018-03-14

    AMH is widely used for assessing ovarian reserve, and it is particularly convenient, because it is thought to have minimal variability throughout the menstrual cycle. However, studies assessing the stability of AMH over the menstrual cycle have been conflicting. The purpose of this study is to determine whether AMH levels vary across the normal menstrual cycle. A multi-center, prospective cohort study conducted at three US centers. Fifty females with regular menstrual cycles aged 18-45 underwent serial venipuncture every 3-5 days starting in the early follicular phase and lasting up to 10 collections. AMH was tested using the Access 2 immunoassay system. Age-adjusted mixed-effect models utilizing data from 384 samples from 50 subjects demonstrated a within subject standard deviation of 0.81 (95% CI 0.75-0.88) with a coefficient of variation of 23.8% across the menstrual cycle and between subject standard deviation of 2.56 (95% CI 2.13-3.21) with a coefficient of variation of 75.1%. Intra-class correlation (ICC) of AMH across the menstrual cycle was 0.91. Overall, AMH levels, using the automated Access AMH assay, appear to be relatively stable across the menstrual cycle. Fluctuations, if any, appear to be small, and therefore, clinicians may advise patients to have AMH levels drawn at any time in the cycle.

  5. Reliability and Validity of a Survey of Cat Caregivers on Their Cats’ Socialization Level in the Cat’s Normal Environment

    Directory of Open Access Journals (Sweden)

    Margaret Slater

    2013-12-01

    Full Text Available Stray cats routinely enter animal welfare organizations each year and shelters are challenged with determining the level of human socialization these cats may possess as quickly as possible. However, there is currently no standard process to guide this determination. This study describes the development and validation of a caregiver survey designed to be filled out by a cat’s caregiver so it accurately describes a cat’s personality, background, and full range of behavior with people when in its normal environment. The results from this survey provided the basis for a socialization score that ranged from unsocialized to well socialized with people. The quality of the survey was evaluated based on inter-rater and test-retest reliability and internal consistency and estimates of construct and criterion validity. In general, our results showed moderate to high levels of inter-rater (median of 0.803, range 0.211–0.957 and test-retest agreement (median 0.92, range 0.211–0.999. Cronbach’s alpha showed high internal consistency (0.962. Estimates of validity did not highlight any major shortcomings. This survey will be used to develop and validate an effective assessment process that accurately differentiates cats by their socialization levels towards humans based on direct observation of cats’ behavior in an animal shelter.

  6. High grade intraepithelial neoplasia of prostate is associated with values of prostate specific antigen related parameters intermediate between prostate cancer and normal levels

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    Nermina Obralic

    2011-11-01

    Full Text Available High grade prostatic intraepithelial neoplasia (HGPIN is widely regarded as the precancerous. The aim of this study was to determine PSA related parameters in patients with initial PSA values 2-10 ng/mL and diagnosis of HGPIN without finding carcinoma at the time of their first needle biopsy. Study groups consisted of 100 men who were diagnosed HGPIN, 84 with cancer and 183 with benign hyperplasia on first biopsy of prostate. Total PSA and free PSA were measured and ratio free/total PSA and PSA density calculated. Mean values of these parameters were compared, and receiver operating characteristic curves were used for comparison of PSA related parameters to discriminate groups of patients. Total PSA, free PSA level and PSA density in patients with HGPIN (6.388 ng/mL did not differ significantly compared to prostate carcinoma (6.976 ng/mL or benign prostatic hyperplasia (6.07 ng/mL patients. Patients with HGPIN had significantly higher ratio free/total PSA than those with prostate carcinoma (0.168 vs 0.133, but significantly lower than patients with benign prostatic hyperplasia (0.168 vs 0.185. Ratio of free/total PSA significantly discriminate HGPIN from prostate carcinoma with sensitivity 84.52 and specify 45.00 at cut-off point of ≤ 0.18. Values of PSA, free PSA and ratio free/total PSA in cases of HGPIN appear to be intermediate between prostate cancer and normal levels. Ratio of free/total PSA may help in decision to repeat biopsies in the presence of HGPIN on biopsy, without concomitant prostate cancer, in patients suitable for curative treatment, with normal digito-rectal examination and trans-rectal sonography.

  7. Correlation of cardiac Troponin I levels (10 folds upper limit of normal) and extent of coronary artery disease in Non-ST elevation myocardial infarction

    International Nuclear Information System (INIS)

    Qadir, F.; Khan, M.; Hanif, B.; Lakhani, S.L.; Farooq, S.

    2010-01-01

    Objective: To determine the correlation of cardiac troponin I (cTnI) 10 folds upper limit of normal (ULN) and extent of coronary artery disease (CAD) in Non-ST-elevation myocardial infarction (NSTEMI). Methods: A cross-sectional study was conducted on 230 consecutive NSTEMI patients admitted in Tabba Heart Institute, Karachi between April to December 2008. cTnI was measured using MEIA method. All patients underwent coronary angiography in the index hospitalization. Stenosis > 70% in any of the three major epicardial vessels was considered significant CAD. Extent of CAD was defined as significant single, two or three vessel CAD. Chi-square test was applied to test the association between cTnI levels and CAD extent. Results: Out of 230 patients, in 111 patients with cTnI levels 10 folds ULN, 23(19.3%) had single vessel, 37(31.1 %) had two vessel and 55(46.2%) had three vessel significant CAD. The results suggest that there was an insignificant association between the cTnI levels and single vessel, two vessel and the overall CAD extent (p= 0.35, p= 0.21 and p= 0.13 respectively), however there was a statistically significant association between the cTnI levels and three vessel CAD (p < 0.04). Conclusion: Higher cTnI levels are associated with an increased proportion of severe three vessel CAD involvement. Prompt identification and referral of this patient subset to early revascularization strategies would improve clinical outcomes. (author)

  8. The effects of listening environment and earphone style on preferred listening levels of normal hearing adults using an MP3 player.

    Science.gov (United States)

    Hodgetts, William E; Rieger, Jana M; Szarko, Ryan A

    2007-06-01

    The main objective of this study was to determine the influence of listening environment and earphone style on the preferred-listening levels (PLLs) measured in users' ear canals with a commercially-available MP3 player. It was hypothesized that listeners would prefer higher levels with earbud headphones as opposed to over-the-ear headphones, and that the effects would depend on the environment in which the user was listening. A secondary objective was to use the measured PLLs to determine the permissible listening duration to reach 100% daily noise dose. There were two independent variables in this study. The first, headphone style, had three levels: earbud, over-the-ear, and over-the-ear with noise reduction (the same headphones with a noise reduction circuit). The second, environment, also had 3 levels: quiet, street noise and multi-talker babble. The dependent variable was ear canal A-weighted sound pressure level. A 3 x 3 within-subjects repeated-measures ANOVA was used to analyze the data. Thirty-eight normal hearing adults were recruited from the Faculty of Rehabilitation Medicine at the University of Alberta. Each subject listened to the same song and adjusted the level until it "sounded best" to them in each of the 9 conditions. Significant main effects were found for both the headphone style and environment factors. On average, listeners had higher preferred listening levels with the earbud headphones, than with the over-the-ear headphones. When the noise reduction circuit was used with the over-the-ear headphones, the average PLL was even lower. On average, listeners had higher PLLs in street noise than in multi-talker babble and both of these were higher than the PLL for the quiet condition. The interaction between headphone style and environment was also significant. Details of individual contrasts are explored. Overall, PLLs were quite conservative, which would theoretically allow for extended permissible listening durations. Finally, we investigated

  9. Do obese but metabolically normal women differ in intra-abdominal fat and physical activity levels from those with the expected metabolic abnormalities? A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Walker Mark

    2010-11-01

    Full Text Available Abstract Background Obesity remains a major public health problem, associated with a cluster of metabolic abnormalities. However, individuals exist who are very obese but have normal metabolic parameters. The aim of this study was to determine to what extent differences in metabolic health in very obese women are explained by differences in body fat distribution, insulin resistance and level of physical activity. Methods This was a cross-sectional pilot study of 39 obese women (age: 28-64 yrs, BMI: 31-67 kg/m2 recruited from community settings. Women were defined as 'metabolically normal' on the basis of blood glucose, lipids and blood pressure. Magnetic Resonance Imaging was used to determine body fat distribution. Detailed lifestyle and metabolic profiles of participants were obtained. Results Women with a healthy metabolic profile had lower intra-abdominal fat volume (geometric mean 4.78 l [95% CIs 3.99-5.73] vs 6.96 l [5.82-8.32] and less insulin resistance (HOMA 3.41 [2.62-4.44] vs 6.67 [5.02-8.86] than those with an abnormality. The groups did not differ in abdominal subcutaneous fat volume (19.6 l [16.9-22.7] vs 20.6 [17.6-23.9]. A higher proportion of those with a healthy compared to a less healthy metabolic profile met current physical activity guidelines (70% [95% CIs 55.8-84.2] vs 25% [11.6-38.4]. Intra-abdominal fat, insulin resistance and physical activity make independent contributions to metabolic status in very obese women, but explain only around a third of the variance. Conclusion A sub-group of women exists who are metabolically normal despite being very obese. Differences in fat distribution, insulin resistance, and physical activity level are associated with metabolic differences in these women, but account only partially for these differences. Future work should focus on strategies to identify those obese individuals most at risk of the negative metabolic consequences of obesity and on identifying other factors that

  10. Birkhoff normalization

    NARCIS (Netherlands)

    Broer, H.; Hoveijn, I.; Lunter, G.; Vegter, G.

    2003-01-01

    The Birkhoff normal form procedure is a widely used tool for approximating a Hamiltonian systems by a simpler one. This chapter starts out with an introduction to Hamiltonian mechanics, followed by an explanation of the Birkhoff normal form procedure. Finally we discuss several algorithms for

  11. Serum fatty acid composition in normal Japanese and its relationship with dietary fish and vegetable oil contents and blood lipid levels.

    Science.gov (United States)

    Nakamura, T; Takebe, K; Tando, Y; Arai, Y; Yamada, N; Ishii, M; Kikuchi, H; Machida, K; Imamura, K; Terada, A

    1995-01-01

    A survey was conducted on 110 normal Japanese adults (55 men and 55 women) to determine their caloric intake, dietary fat content and its origin (animal, plant, or marine). In addition, their blood lipid levels and fatty acid compositions were examined. Men in their 30s-50s consumed 2,600-2,800 calories and 60 g of fats, while women in the same age range consumed 2,000-2,200 calories and 52-58 g of fats. In both sexes, caloric, fat, and cholesterol intakes were lower for those in their 60s but protein and crude fiber consumption remained generally unchanged. When the dietary fats were classified according to origin, men and women in their 30s were found to consume less oil of marine origin. This appeared to be the result of a western style diet for Japanese adults in their 30s. Compared with men, women exhibited lower blood lipid levels. As age increased, the total cholesterol level of the blood rose in women. Thus the blood lipid level was generally equal in the two groups in their 60s. There was a positive correlation between the blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels and dietary consumption of fish oil. The marine/plant lipid ratio was positively correlated with the blood EPA/arachidonic acid ratio. Therefore, it was believed that the origin of the dietary fats consumed is a factor in determining the blood fatty acid profile. The linoleic acid (18:2), arachidonic acid (20:4), and 18:2 + 20:4 contents were negatively correlated to the total cholesterol level in the blood but positively correlated to the HDL-cholesterol level. Polyunsaturated fatty acids (18:2 + 20:4 + 20:5 + 22:6) were negatively correlated with the blood triglyceride level. From the findings presented above, we concluded that dietary fats not derived from animal sources should be classified into fish and vegetable oils to evaluate their dietary significance. We also noted that Japanese in their 30s consume less fish oil, indicating the western trend in their

  12. Genomic data reveal Toxoplasma gondii differentiation mutants are also impaired with respect to switching into a novel extracellular tachyzoite state.

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    Pamela J Lescault

    2010-12-01

    Full Text Available Toxoplasma gondii pathogenesis includes the invasion of host cells by extracellular parasites, replication of intracellular tachyzoites, and differentiation to a latent bradyzoite stage. We present the analysis of seven novel T. gondii insertional mutants that do not undergo normal differentiation to bradyzoites. Microarray quantification of the variation in genome-wide RNA levels for each parasite line and times after induction allowed us to describe states in the normal differentiation process, to analyze mutant lines in the context of these states, and to identify genes that may have roles in initiating the transition from tachyzoite to bradyzoite. Gene expression patterns in wild-type parasites undergoing differentiation suggest a novel extracellular state within the tachyzoite stage. All mutant lines exhibit aberrant regulation of bradyzoite gene expression and notably some of the mutant lines appear to exhibit high proportions of the intracellular tachyzoite state regardless of whether they are intracellular or extracellular. In addition to the genes identified by the insertional mutagenesis screen, mixture model analysis allowed us to identify a small number of genes, in mutants, for which expression patterns could not be accounted for using the three parasite states--genes that may play a mechanistic role in switching from the tachyzoite to bradyzoite stage.

  13. Extracellular vesicles: Exosomes, microvesicles, and friends

    NARCIS (Netherlands)

    Raposo, G.; Stoorvogel, W.|info:eu-repo/dai/nl/074352385

    2013-01-01

    Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for

  14. Inhibition of intestinal bile acid transporter Slc10a2 improves triglyceride metabolism and normalizes elevated plasma glucose levels in mice.

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    Thomas Lundåsen

    Full Text Available Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2 and ob/ob mice treated with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, and when challenged with a sucrose-rich diet, they displayed a reduced response in hepatic TG production as observed from the mRNA levels of several key enzymes in fatty acid synthesis. This effect was paralleled by a diminished induction of mature sterol regulatory element-binding protein 1c (Srebp1c. Unexpectedly, the SR-diet induced intestinal fibroblast growth factor (FGF 15 mRNA and normalized bile acid synthesis in Slc10a2-/- mice. Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose, insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes. These responses are contrary to those reported following treatment of mice with a bile acid binding resin. Moreover, when key metabolic signal transduction pathways in the liver were investigated, those of Mek1/2-Erk1/2 and Akt were blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in the diabetic ob/ob model it also reduces glucose and insulin levels. Hence, targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia and diabetes.

  15. Personalised iron supply for prophylaxis and treatment of pregnant women as a way to ensure normal iron levels in their breast milk.

    Science.gov (United States)

    Marin, G H; Mestorino, N; Errecalde, J; Huber, B; Uriarte, A; Orchuela, J

    2012-02-22

    Because the characteristics of all body fluids depends on patient's health status, is it possible that disadvantaged and socially vulnerable mothers may have lower amounts of iron in their breast milk, and that their babies receive lower content of the mineral for their normal growth and development. Assuring a preventive treatment of the mother might solve this problem. To demonstrate breast milk iron content from disadvantaged mothers and impact of personalized iron supplementation program. cross-sectional study. Breast milk samples were obtained for ferritin analysis. Health's services usually provides free folic acid and iron treatment however, treatment compliance is low. Patients were random in two groups: "A: Controls" that had free iron tablets available from Health Centre; and "B: Intervention" group where patients accepted to be periodically contacted at home by health's team for personalized iron dispensation. 360 patients were included. Profilaxis and treatment compliance were 100% and 97,6% for B group while for "Control" one was 63% and 34%(p0.0001). Higher breast milk iron levels were detected in Intervention's mothers compared with control's patients (p0.007). Personalized iron prophylaxis and treatment increased breast milk iron levels. Public health policy must ensure iron dispensation for each underserved mother in order to reduce children problems associate to iron deficiency during the first year of their life.

  16. Effects of blood glucose level on 18F-FDG uptake for PET/CT in normal organs: A systematic review.

    Directory of Open Access Journals (Sweden)

    Clarice Sprinz

    Full Text Available To perform a systematic review of the effect of blood glucose levels on 2-Deoxy-2-[18F]fluoro-D-glucose (18F-FDG uptake in normal organs.We searched the MEDLINE, EMBASE and Cochrane databases through 22 April 2017 to identify all relevant studies using the keywords "PET/CT" (positron emission tomography/computed tomography, "standardized uptake value" (SUV, "glycemia," and "normal." Analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Maximum and mean SUVs and glycemia were the main parameters analyzed. To objectively measure the magnitude of the association between glycemia and 18F-FDG uptake in different organs, we calculated the effect size (ES and the coefficient of determination (R2 whenever possible.The literature search yielded 225 results, and 14 articles met the inclusion criteria; studies included a total of 2714 (range, 51-557 participants. The brain SUV was related significantly and inversely to glycemia (ES = 1.26; R2 0.16-0.58. Although the liver and mediastinal blood pool were significantly affected by glycemia, the magnitudes of these associations were small (ES = 0.24-0.59, R2 = 0.01-0.08 and negligible (R2 = 0.02, respectively. Lung, bone marrow, tumor, spleen, fat, bowel, and stomach 18F-FDG uptakes were not influenced by glycemia. Individual factors other than glycemia can also affect 18F-FDG uptake in different organs, and body mass index appears to be the most important of these factors.The impact of glycemia on SUVs in most organs is either negligible or too small to be clinically significant. The brain SUV was the only value largely affected by glycemia.

  17. Simple serum markers for significant liver inflammation in chronic hepatitis B patients with an alanine aminotransferase level lower than 2 times upper limit of normal

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    LI Qiang

    2016-06-01

    Full Text Available ObjectiveTo investigate the simple serum markers for significant liver inflammation in chronic hepatitis B (CHB patients with an alanine aminotransferase (ALT level of <2 times upper limit of normal (ULN. MethodsThe clinical data of 278 CHB patients with ALT <2×ULN (ULN=40 U/L were analyzed retrospectively. Significant liver inflammation was defined as a liver inflammatory activity grade (G ≥2. The t-test was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis rank sum test was used for non-normally distributed continuous data; the chi-square test was used for comparison of categorical data between groups. Multivariate logistic regression analysis was used to identify independent predictors for significant liver inflammation in CHB patients with ALT <2×ULN. The receiver operating characteristic (ROC curve was used to evaluate the diagnostic value of serum markers in significant liver inflammation. ResultsOf the 278 CHB patients enrolled, 175 (62.9% had no significant liver inflammation (G0-1 group and 103 (37.1% had significant liver inflammation (G2-4 group. There were significant differences in ALT, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase (GGT, albumin, globulin, prothrombin time (PT, platelet, absolute neutrophil count, hyaluronic acid (HA, glycocholic acid, precollagen Ⅲ, and collagen type Ⅳ(ⅣC between the two groups (all P<0.05. The multivariate regression analysis showed that GGT, PT, ⅣC, and HA were independent predictors for significant liver inflammation in CHB patients with ALT<2×ULN (OR=1.015, 1.600, 1.151, and 1.014, P=0.008, 0.021, 0.003, and 0.018. The areas under the ROC curve for GGT, PT, IVC, and HA to diagnose significant liver inflammation were 0.804, 0.722, 0.707, and 0.632, respectively. The cut-off value of 48.5 U/L for GGT to predict significant liver inflammation had a specificity of 90.3% and a negative

  18. Extracellular secretion of recombinant proteins

    Science.gov (United States)

    Linger, Jeffrey G.; Darzins, Aldis

    2014-07-22

    Nucleic acids encoding secretion signals, expression vectors containing the nucleic acids, and host cells containing the expression vectors are disclosed. Also disclosed are polypeptides that contain the secretion signals and methods of producing polypeptides, including methods of directing the extracellular secretion of the polypeptides. Exemplary embodiments include cellulase proteins fused to secretion signals, methods to produce and isolate these polypeptides, and methods to degrade lignocellulosic biomass.

  19. Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone.

    Science.gov (United States)

    Gonen, Nitzan; Quinn, Alexander; O'Neill, Helen C; Koopman, Peter; Lovell-Badge, Robin

    2017-01-01

    During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES), which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Although human patients heterozygous for null mutations in SOX9, which are assumed to have 50% of normal expression, often show XY female sex reversal, mice deleted for one copy of Sox9 do not. Consistent with this, we did not observe sex reversal in either TESCO-/- or TES-/- XY embryos or adult mice. However, embryos carrying both a conditional Sox9 null allele and the TES deletion developed ovotestes. Quantitative analysis of these revealed levels of 23% expression of Sox9 compared to wild type, and a significant increase in the expression of the granulosa cell marker Foxl2. This indicates that the threshold in mice where sex reversal begins to be seen is about half that of the ~50% levels predicted in humans. Our results demonstrate that TES/TESCO is a crucial enhancer regulating Sox9 expression in the gonad, but point to the existence of additional enhancers that act redundantly.

  20. Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone.

    Directory of Open Access Journals (Sweden)

    Nitzan Gonen

    2017-01-01

    Full Text Available During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES, which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Although human patients heterozygous for null mutations in SOX9, which are assumed to have 50% of normal expression, often show XY female sex reversal, mice deleted for one copy of Sox9 do not. Consistent with this, we did not observe sex reversal in either TESCO-/- or TES-/- XY embryos or adult mice. However, embryos carrying both a conditional Sox9 null allele and the TES deletion developed ovotestes. Quantitative analysis of these revealed levels of 23% expression of Sox9 compared to wild type, and a significant increase in the expression of the granulosa cell marker Foxl2. This indicates that the threshold in mice where sex reversal begins to be seen is about half that of the ~50% levels predicted in humans. Our results demonstrate that TES/TESCO is a crucial enhancer regulating Sox9 expression in the gonad, but point to the existence of additional enhancers that act redundantly.

  1. The effect of speaking rate on serial-order sound-level errors in normal healthy controls and persons with aphasia.

    Science.gov (United States)

    Fossett, Tepanta R D; McNeil, Malcolm R; Pratt, Sheila R; Tompkins, Connie A; Shuster, Linda I

    Although many speech errors can be generated at either a linguistic or motoric level of production, phonetically well-formed sound-level serial-order errors are generally assumed to result from disruption of phonologic encoding (PE) processes. An influential model of PE (Dell, 1986; Dell, Burger & Svec, 1997) predicts that speaking rate should affect the relative proportion of these serial-order sound errors (anticipations, perseverations, exchanges). These predictions have been extended to, and have special relevance for persons with aphasia (PWA) because of the increased frequency with which speech errors occur and because their localization within the functional linguistic architecture may help in diagnosis and treatment. Supporting evidence regarding the effect of speaking rate on phonological encoding has been provided by studies using young normal language (NL) speakers and computer simulations. Limited data exist for older NL users and no group data exist for PWA. This study tested the phonologic encoding properties of Dell's model of speech production (Dell, 1986; Dell,et al., 1997), which predicts that increasing speaking rate affects the relative proportion of serial-order sound errors (i.e., anticipations, perseverations, and exchanges). The effects of speech rate on the error ratios of anticipation/exchange (AE), anticipation/perseveration (AP) and vocal reaction time (VRT) were examined in 16 normal healthy controls (NHC) and 16 PWA without concomitant motor speech disorders. The participants were recorded performing a phonologically challenging (tongue twister) speech production task at their typical and two faster speaking rates. A significant effect of increased rate was obtained for the AP but not the AE ratio. Significant effects of group and rate were obtained for VRT. Although the significant effect of rate for the AP ratio provided evidence that changes in speaking rate did affect PE, the results failed to support the model derived predictions

  2. Degenerated human intervertebral discs contain autoantibodies against extracellular matrix proteins

    Directory of Open Access Journals (Sweden)

    S Capossela

    2014-04-01

    Full Text Available Degeneration of intervertebral discs (IVDs is associated with back pain and elevated levels of inflammatory cells. It has been hypothesised that discogenic pain is a direct result of vascular and neural ingrowth along annulus fissures, which may expose the avascular nucleus pulposus (NP to the systemic circulation and induce an autoimmune reaction. In this study, we confirmed our previous observation of antibodies in human degenerated and post-traumatic IVDs cultured in vitro. We hypothesised that the presence of antibodies was due to an autoimmune reaction against specific proteins of the disc. Furthermore we identified antigens which possibly trigger an autoimmune response in degenerative disc diseases. We demonstrated that degenerated and post-traumatic IVDs contain IgG antibodies against typical extracellular proteins of the disc, particularly proteins of the NP. We identified IgGs against collagen type II and aggrecan, confirming an autoimmune reaction against the normally immune privileged NP. We also found specific IgGs against collagens types I and V, but not against collagen type III. In conclusion, this study confirmed the association between disc degeneration and autoimmunity, and may open the avenue for future studies on developing prognostic, diagnostic and therapy-monitoring markers for degenerative disc diseases.

  3. Effects of free-air CO2 enrichment on adventitious root development of rice under low and normal soil nitrogen levels

    Directory of Open Access Journals (Sweden)

    Chengming Sun

    2014-08-01

    Full Text Available Free air CO2 enrichment (FACE and nitrogen (N have marked effects on rice root growth, and numerical simulation can explain these effects. To further define the effects of FACE on root growth of rice, an experiment was performed, using the hybrid indica cultivar Xianyou 63. The effects of increasing atmospheric CO2 concentration [CO2], 200 μmol mol− 1 higher than ambient, on the growth of rice adventitious roots were evaluated, with two levels of N: low (LN, 125 kg ha− 1 and normal (NN, 250 kg ha− 1. The results showed a significant increase in both adventitious root number (ARN and adventitious root length (ARL under FACE treatment. The application of nitrogen also increased ARN and ARL, but these increases were smaller than that under FACE treatment. On the basis of the FACE experiment, numerical models for rice adventitious root number and length were constructed with time as the driving factor. The models illustrated the dynamic development of rice adventitious root number and length after transplanting, regulated either by atmospheric [CO2] or by N application. The simulation result was supported by statistical tests comparing experimental data from different years, and the model yields realistic predictions of root growth. These results suggest that the models have strong predictive potential under conditions of atmospheric [CO2] rises in the future.

  4. Measurement of spontaneous DNA damage and DNA repair capacity in healthy adult individuals from high and normal level natural radiation areas of Kerala, India

    International Nuclear Information System (INIS)

    Vivek Kumar, P.R.; Jaikrishan, G.; Das, Birajalaxmi

    2014-01-01

    Inhabitants of the south west coastal areas of Kerala receive high level natural radiation due to the presence of monazite ( 232 Th) in the beach sand. This provides a unique opportunity to investigate the biological effects of high level natural radiation on humans. This study evaluate basal DNA damage in 149 healthy adult male subjects (104 from high level natural radiation areas (HLNRA, > 1mSv year -1 ) and 45 from normal level natural radiation area (NLNRA, d''1mSv year -1 ) by the alkaline comet assay. Oxidative DNA damage (ENDO III, FPG and hOGG1-sensitive sites) was measured by the enzyme modified comet assay. Induction and rejoining of DNA strand breaks was measured after irradiating peripheral blood lymphocytes with 2 Gy or 4 Gy gamma radiation. Basal damage due to age and residential area of the donors showed significant interaction (P=0.001), when all subjects were analyzed using a general linear model (GLM). In subgroup analysis, basal damage increased with age in subjects from the NLNRA (P=0.007), while a significant negative correlation (P=0.01) was observed in subjects from HLNRA. Oxidative DNA damage was not influenced by age, smoking habit or residential area in the entire sample. Subjects of high dose group from HLNRA (>5.75 mSv/y, N=34) showed a significant reduction in the induction of DNA damage after 2 Gy (P=0.03) and 4 Gy (P=0.05) compared to subjects form NLNRA. The study showed increased rejoining of DNA strand breaks in subjects from HLNRA when measured at 7 minutes after irradiation (P=0.04). In this pilot study, a low basal damage in elderly subjects from HLNRA and a reduced induction of DNA damage after 2 Gy and 4 Gy irradiation in high dose group subjects from HLNRA might suggest a possible role of chronic low dose natural radiation on the induction of an in vivo radio adaptive response. However, our findings need more validation in a larger study population. (author)

  5. Elevated 1-h post-challenge plasma glucose levels in subjects with normal glucose tolerance or impaired glucose tolerance are associated with whole blood viscosity.

    Science.gov (United States)

    Marini, Maria Adelaide; Fiorentino, Teresa Vanessa; Andreozzi, Francesco; Mannino, Gaia Chiara; Perticone, Maria; Sciacqua, Angela; Perticone, Francesco; Sesti, Giorgio

    2017-08-01

    It has been suggested that glucose levels ≥155 mg/dl at 1-h during an oral glucose tolerance test (OGTT) may predict development of type 2 diabetes and cardiovascular events among adults with normal glucose tolerance (NGT 1 h-high). Studies showed a link between increased blood viscosity and type 2 diabetes. However, whether blood viscosity is associated with dysglycemic conditions such as NGT 1 h-high, impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) is unsettled. 1723 non-diabetic adults underwent biochemical evaluation and OGTT. A validated formula based on hematocrit and total plasma proteins was employed to estimate whole blood viscosity. Subjects were categorized into NGT with 1 h glucose h-low), NGT-1 h-high, IFG and/or IGT. Hematocrit and blood viscosity values appeared significantly higher in individuals with NGT 1 h-high, IFG and/or IGT as compared to NGT 1 h-low subjects. Blood viscosity was significantly correlated with age, waist circumference, blood pressure, HbA1c, fasting, 1- and 2-h post-challenge insulin levels, total cholesterol and low-density lipoprotein, triglycerides, fibrinogen, white blood cell, and inversely correlated with high-density lipoprotein and insulin sensitivity. Of the four glycemic parameters, 1-h post-challenge glucose showed the strongest correlation with blood viscosity (β = 0.158, P h post-challenge plasma glucose. They also suggest that a subgroup of NGT individuals with 1-h post-challenge plasma >155 mg/dl have increased blood viscosity comparable to that observed in subjects with IFG and/or IGT.

  6. Construction and characterization of normalized cDNA libraries by 454 pyrosequencing and estimation of DNA methylation levels in three distantly related termite species.

    Directory of Open Access Journals (Sweden)

    Yoshinobu Hayashi

    Full Text Available In termites, division of labor among castes, categories of individuals that perform specialized tasks, increases colony-level productivity and is the key to their ecological success. Although molecular studies on caste polymorphism have been performed in termites, we are far from a comprehensive understanding of the molecular basis of this phenomenon. To facilitate future molecular studies, we aimed to construct expressed sequence tag (EST libraries covering wide ranges of gene repertoires in three representative termite species, Hodotermopsis sjostedti, Reticulitermes speratus and Nasutitermes takasagoensis. We generated normalized cDNA libraries from whole bodies, except for guts containing microbes, of almost all castes, sexes and developmental stages and sequenced them with the 454 GS FLX titanium system. We obtained >1.2 million quality-filtered reads yielding >400 million bases for each of the three species. Isotigs, which are analogous to individual transcripts, and singletons were produced by assembling the reads and annotated using public databases. Genes related to juvenile hormone, which plays crucial roles in caste differentiation of termites, were identified from the EST libraries by BLAST search. To explore the potential for DNA methylation, which plays an important role in caste differentiation of honeybees, tBLASTn searches for DNA methyltransferases (dnmt1, dnmt2 and dnmt3 and methyl-CpG binding domain (mbd were performed against the EST libraries. All four of these genes were found in the H. sjostedti library, while all except dnmt3 were found in R. speratus and N. takasagoensis. The ratio of the observed to the expected CpG content (CpG O/E, which is a proxy for DNA methylation level, was calculated for the coding sequences predicted from the isotigs and singletons. In all of the three species, the majority of coding sequences showed depletion of CpG O/E (less than 1, and the distributions of CpG O/E were bimodal, suggesting

  7. Construction and characterization of normalized cDNA libraries by 454 pyrosequencing and estimation of DNA methylation levels in three distantly related termite species.

    Science.gov (United States)

    Hayashi, Yoshinobu; Shigenobu, Shuji; Watanabe, Dai; Toga, Kouhei; Saiki, Ryota; Shimada, Keisuke; Bourguignon, Thomas; Lo, Nathan; Hojo, Masaru; Maekawa, Kiyoto; Miura, Toru

    2013-01-01

    In termites, division of labor among castes, categories of individuals that perform specialized tasks, increases colony-level productivity and is the key to their ecological success. Although molecular studies on caste polymorphism have been performed in termites, we are far from a comprehensive understanding of the molecular basis of this phenomenon. To facilitate future molecular studies, we aimed to construct expressed sequence tag (EST) libraries covering wide ranges of gene repertoires in three representative termite species, Hodotermopsis sjostedti, Reticulitermes speratus and Nasutitermes takasagoensis. We generated normalized cDNA libraries from whole bodies, except for guts containing microbes, of almost all castes, sexes and developmental stages and sequenced them with the 454 GS FLX titanium system. We obtained >1.2 million quality-filtered reads yielding >400 million bases for each of the three species. Isotigs, which are analogous to individual transcripts, and singletons were produced by assembling the reads and annotated using public databases. Genes related to juvenile hormone, which plays crucial roles in caste differentiation of termites, were identified from the EST libraries by BLAST search. To explore the potential for DNA methylation, which plays an important role in caste differentiation of honeybees, tBLASTn searches for DNA methyltransferases (dnmt1, dnmt2 and dnmt3) and methyl-CpG binding domain (mbd) were performed against the EST libraries. All four of these genes were found in the H. sjostedti library, while all except dnmt3 were found in R. speratus and N. takasagoensis. The ratio of the observed to the expected CpG content (CpG O/E), which is a proxy for DNA methylation level, was calculated for the coding sequences predicted from the isotigs and singletons. In all of the three species, the majority of coding sequences showed depletion of CpG O/E (less than 1), and the distributions of CpG O/E were bimodal, suggesting the presence of

  8. The Impact of Energy Substrates, Hormone Level and Subject-Related Factors on Physiologic Myocardial {sup 18}F-FDG Uptake in Normal Humans

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Juhye; Kong, Eunjung; Chun, Kyungah; Cho, Ihnho [Yeung-Nam Univ. Hoepital, Daegu (Korea, Republic of)

    2013-12-15

    In a whole-body {sup 18}F-FDG PET/CT, non-specific {sup 18}F-FDG uptake of the myocardium is a common finding and can be very variable, ranging from background activity to intense accumulation and inhomogeneity. We investigated the effect of energy substrates and plasma/serum hormones that may have an influence on myocardial {sup 18}F-FDG uptake. F-FDG PET/CT was performed on 100 normal volunteers from November 2007 to August 2008. Blood samples were taken just before {sup 18}F-FDG injection from all subjects. Myocardial {sup 18}F-FDG uptake was measured as the mean (SUVmean) and maximal (SUV{sub max}) standardized uptake value. The myocardium was delineated on the PET/CT image by a manual volume of interest (VOI).We analyzed the influence of age, sex, presence of diabetes, fasting duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA), epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI). Overall, 92 subjects (mean age 50.28±8.30, male 57) were enrolled. The average of myocardial SUVmean was 2.08 and of myocardial SUV{sub max} was 4.57, respectively and there was a strong linear correlation between SUVmean and SUV{sub max} (r =0.98). FFA and fasting duration showed significant negative correlation with myocardial {sup 18}F-FDG uptake, respectively (r =-0.40 in FFA; r =-0.41 in fasting duration). No significant relationships were observed between myocardial uptake and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate, EPi, NEp, free T3, free T4, TSH and BMI. Myocardial {sup 18}F-FDG uptake decreases with longer fasting duration and higher FFA level in normal humans. Modulating myocardial uptake could improve {sup 18}F-FDG PET/CT imaging for specific oncologic and cardiovascular indications.

  9. Regulation of pituitary hormones and cell proliferation by components of the extracellular matrix

    Directory of Open Access Journals (Sweden)

    M. Paez-Pereda

    2005-10-01

    Full Text Available The extracellular matrix is a three-dimensional network of proteins, glycosaminoglycans and other macromolecules. It has a structural support function as well as a role in cell adhesion, migration, proliferation, differentiation, and survival. The extracellular matrix conveys signals through membrane receptors called integrins and plays an important role in pituitary physiology and tumorigenesis. There is a differential expression of extracellular matrix components and integrins during the pituitary development in the embryo and during tumorigenesis in the adult. Different extracellular matrix components regulate adrenocorticotropin at the level of the proopiomelanocortin gene transcription. The extracellular matrix also controls the proliferation of adrenocorticotropin-secreting tumor cells. On the other hand, laminin regulates the production of prolactin. Laminin has a dynamic pattern of expression during prolactinoma development with lower levels in the early pituitary hyperplasia and a strong reduction in fully grown prolactinomas. Therefore, the expression of extracellular matrix components plays a role in pituitary tumorigenesis. On the other hand, the remodeling of the extracellular matrix affects pituitary cell proliferation. Matrix metalloproteinase activity is very high in all types of human pituitary adenomas. Matrix metalloproteinase secreted by pituitary cells can release growth factors from the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis.

  10. Production of extracellular fatty acid using engineered Escherichia coli

    Directory of Open Access Journals (Sweden)

    Liu Hui

    2012-04-01

    Full Text Available Abstract Background As an alternative for economic biodiesel production, the microbial production of extracellular fatty acid from renewable resources is receiving more concerns recently, since the separation of fatty acid from microorganism cells is normally involved in a series of energy-intensive steps. Many attempts have been made to construct fatty acid producing strains by targeting genes in the fatty acid biosynthetic pathway, while few studies focused on the cultivation process and the mass transfer kinetics. Results In this study, both strain improvements and cultivation process strategies were applied to increase extracellular fatty acid production by engineered Escherichia coli. Our results showed overexpressing ‘TesA and the deletion of fadL in E. coli BL21 (DE3 improved extracellular fatty acid production, while deletion of fadD didn’t strengthen the extracellular fatty acid production for an undetermined mechanism. Moreover, the cultivation process controls contributed greatly to extracellular fatty acid production with respect to titer, cell growth and productivity by adjusting the temperature, adding ampicillin and employing on-line extraction. Under optimal conditions, the E. coli strain (pACY-‘tesA-ΔfadL produced 4.8 g L−1 extracellular fatty acid, with the specific productivity of 0.02 g h−1 g−1dry cell mass, and the yield of 4.4% on glucose, while the ratios of cell-associated fatty acid versus extracellular fatty acid were kept below 0.5 after 15 h of cultivation. The fatty acids included C12:1, C12:0, C14:1, C14:0, C16:1, C16:0, C18:1, C18:0. The composition was dominated by C14 and C16 saturated and unsaturated fatty acids. Using the strain pACY-‘tesA, similar results appeared under the same culture conditions and the titer was also much higher than that ever reported previously, which suggested that the supposedly superior strain did not necessarily perform best for the efficient production of desired

  11. Individual levels of plasma alpha 2-antiplasmin and alpha 2-macroglobulin during the normal menstrual cycle and in women on oral contraceptives low in oestrogen

    DEFF Research Database (Denmark)

    Jespersen, J; Sidelmann, Johannes Jakobsen

    1983-01-01

    Determinations of alpha 2-antiplasmin and alpha 2-macroglobulin were made in plasma samples collected during one normal or hormone induced cycle in 15 normal women and 11 women using oral contraceptives containing 30 micrograms ethinyl oestradiol and 150 micrograms levo-norgestrel. The immediate ...

  12. Filtration recovery of extracellular DNA from environmental water samples

    Science.gov (United States)

    qPCR methods are able to analyze DNA from microbes within hours of collecting water samples, providing the promptest notification and public awareness possible when unsafe pathogenic levels are reached. Health risk, however, may be overestimated by the presence of extracellular ...

  13. Extracellular Vesicles in Hematological Disorders

    Directory of Open Access Journals (Sweden)

    Anat Aharon

    2014-10-01

    Full Text Available Extracellular vesicles (EVs, comprised of exosomes, microparticles, apoptotic bodies, and other microvesicles, are shed from a variety of cells upon cell activation or apoptosis. EVs promote clot formation, mediate pro-inflammatory processes, transfer proteins and miRNA to cells, and induce cell signaling that regulates cell differentiation, proliferation, migration, invasion, and apoptosis. This paper will review the contribution of EVs in hematological disorders, including hemoglobinopathies (sickle cell disease, thalassemia, paroxysmal nocturnal hemoglobinuria, and hematological malignancies (lymphomas, myelomas, and acute and chronic leukemias.

  14. Blood extracellular DNA after irradiation

    International Nuclear Information System (INIS)

    Vladimirov, V.G.; Tishchenko, L.I.; Surkova, E.A.; Vasil'eva, I.N.

    1993-01-01

    It has been shown that blood extracellular DNA of irradiated rats largely consists of the low-molecular DNA and its oligomers. Molecular masses of oligomers are multiple to molecular mass of monomer fragment with nucleosome size. The low-molecular DNA has linear form. The average content of GC-pairs in low-molecular DNA is higher than in total rat's DNA (48.5% against 41.5%). The low-molecular DNA is a part of complex containing RNA, acidic proteins and lipids. It is assumed that the formation of low-molecular DNA is a result of Ca/Mg - dependent nuclear endonuclease action

  15. Production of extracellular nucleic acids by genetically altered bacteria in aquatic-environment microcosms

    International Nuclear Information System (INIS)

    Paul, J.H.; David, A.W.

    1989-01-01

    The factors which affect the production of extracellular DNA by genetically altered strains of Escherichia coli, Pseudomonas aeruginosa, Pseudomonas cepacia, and Bradyrhizobium japonicum in aquatic environments were investigated. Cellular nucleic acids were labeled in vivo by incubation with [ 3 H]thymidine or [ 3 H]adenine, and production of extracellular DNA in marine waters, artificial seawater, or minimal salts media was determined by detecting radiolabeled macromolecules in incubation filtrates. The presence or absence of the ambient microbial community had little effect on the production of extracellular DNA. Three of four organisms produced the greatest amounts of extracellular nucleic acids when incubated in low-salinity media (2% artificial seawater) rather than high-salinity media (10 to 50% artificial seawater). The greatest production of extracellular nucleic acids by P. cepacia occurred at pH 7 and 37 degree C, suggesting that extracellular-DNA production may be a normal physiologic function of the cell. Incubation of labeled P. cepacia cells in water from Bimini Harbor, Bahamas, resulted in labeling of macromolecules of the ambient microbial population. Collectively these results indicate that (i) extracellular-DNA production by genetically altered bacteria released into aquatic environments is more strongly influenced by physicochemical factors than biotic factors, (ii) extracellular-DNA production rates are usually greater for organisms released in freshwater than marine environments, and (iii) ambient microbial populations can readily utilize materials released by these organisms

  16. The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis

    NARCIS (Netherlands)

    Heeneman, Sylvia; Cleutjens, Jack P.; Faber, Birgit C.; Creemers, Esther E.; van Suylen, Robert-Jan; Lutgens, Esther; Cleutjens, Kitty B.; Daemen, Mat J.

    2003-01-01

    The extracellular matrix is no longer seen as the static embedding in which cells reside; it has been shown to be involved in cell proliferation, migration and cell-cell interactions. Turnover of the different extracellular matrix components is an active process with multiple levels of regulation.

  17. Fish to meat intake ratio and cooking oils are associated with hepatitis C virus carriers with persistently normal alanine aminotransferase levels.

    Science.gov (United States)

    Otsuka, Momoka; Uchida, Yuki; Kawaguchi, Takumi; Taniguchi, Eitaro; Kawaguchi, Atsushi; Kitani, Shingo; Itou, Minoru; Oriishi, Tetsuharu; Kakuma, Tatsuyuki; Tanaka, Suiko; Yagi, Minoru; Sata, Michio

    2012-10-01

      Dietary habits are involved in the development of chronic inflammation; however, the impact of dietary profiles of hepatitis C virus carriers with persistently normal alanine transaminase levels (HCV-PNALT) remains unclear. The decision-tree algorithm is a data-mining statistical technique, which uncovers meaningful profiles of factors from a data collection. We aimed to investigate dietary profiles associated with HCV-PNALT using a decision-tree algorithm.   Twenty-seven HCV-PNALT and 41 patients with chronic hepatitis C were enrolled in this study. Dietary habit was assessed using a validated semiquantitative food frequency questionnaire. A decision-tree algorithm was created by dietary variables, and was evaluated by area under the receiver operating characteristic curve analysis (AUROC).   In multivariate analysis, fish to meat ratio, dairy product and cooking oils were identified as independent variables associated with HCV-PNALT. The decision-tree algorithm was created with two variables: a fish to meat ratio and cooking oils/ideal bodyweight. When subjects showed a fish to meat ratio of 1.24 or more, 68.8% of the subjects were HCV-PNALT. On the other hand, 11.5% of the subjects were HCV-PNALT when subjects showed a fish to meat ratio of less than 1.24 and cooking oil/ideal bodyweight of less than 0.23 g/kg. The difference in the proportion of HCV-PNALT between these groups are significant (odds ratio 16.87, 95% CI 3.40-83.67, P = 0.0005). Fivefold cross-validation of the decision-tree algorithm showed an AUROC of 0.6947 (95% CI 0.5656-0.8238, P = 0.0067).   The decision-tree algorithm disclosed that fish to meat ratio and cooking oil/ideal bodyweight were associated with HCV-PNALT. © 2012 The Japan Society of Hepatology.

  18. Extracellular nucleotide signaling in plants

    Energy Technology Data Exchange (ETDEWEB)

    Stacey, Gary [Univ. of Missouri, Columbia, MO (United States)

    2016-09-08

    Over the life of this funded project, our research group identified and characterized two key receptor proteins in plants; one mediating the innate immunity response to chitin and the other elucidating the key receptor for extracellular ATP. In the case of chitin recognition, we recently described the quaternary structure of this receptor, shedding light on how the receptor functions. Perhaps more importantly, we demonstrated that all plants have the ability to recognize both chitin oligomers and lipochitooligosacchardes, fundamentally changing how the community views the evolution of these systems and strategies that might be used, for example, to extend symbiotic nitrogen fixation to non-legumes. Our discovery of DORN1 opens a new chapter in plant physiology documenting conclusively that eATP is an important extracellular signal in plants, as it is in animals. At this point, we cannot predict just how far reaching this discovery may prove to be but we are convinced that eATP signaling is fundamental to plant growth and development and, hence, we believe that the future will be very exciting for the study of DORN1 and its overall function in plants.

  19. Cy5 total protein normalization in Western blot analysis.

    Science.gov (United States)

    Hagner-McWhirter, Åsa; Laurin, Ylva; Larsson, Anita; Bjerneld, Erik J; Rönn, Ola

    2015-10-01

    Western blotting is a widely used method for analyzing specific target proteins in complex protein samples. Housekeeping proteins are often used for normalization to correct for uneven sample loads, but these require careful validation since expression levels may vary with cell type and treatment. We present a new, more reliable method for normalization using Cy5-prelabeled total protein as a loading control. We used a prelabeling protocol based on Cy5 N-hydroxysuccinimide ester labeling that produces a linear signal response. We obtained a low coefficient of variation (CV) of 7% between the ratio of extracellular signal-regulated kinase (ERK1/2) target to Cy5 total protein control signals over the whole loading range from 2.5 to 20.0μg of Chinese hamster ovary cell lysate protein. Corresponding experiments using actin or tubulin as controls for normalization resulted in CVs of 13 and 18%, respectively. Glyceraldehyde-3-phosphate dehydrogenase did not produce a proportional signal and was not suitable for normalization in these cells. A comparison of ERK1/2 signals from labeled and unlabeled samples showed that Cy5 prelabeling did not affect antibody binding. By using total protein normalization we analyzed PP2A and Smad2/3 levels with high confidence. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Assembling of (βLPH) beta-lypothrophine radioimmunoassay. Plasma levels standardization in normal individuals and patients with hypophysis and adrenals diseases

    International Nuclear Information System (INIS)

    Castro, Margaret de.

    1988-01-01

    The present study investigates the extraction and radioimmunoassay (RIA) conditions of plasma βLPH. It was extracted by the activated silicic acid method, with a mean extraction efficiency of 31.6% and a mean intra-extraction variation coefficient of 8.1%. Radioiodination was performed by the chloramine-T method and βLPH 125 I was purified by gel chromatography on Sephadex G100. Estimated specific activity ranged from 100 to 192.8 μCi/μg, with a mean incorporation percentage of 66.6%. The titer of the first antibody was 1:50.000/100 μl. The assay was performed under non-equilibrium conditions, with a pre-incubation period of 24 hours and incubation of 4 hours. Mean immunoreactivity (Bo/Total) was 21.1%, with a mean Blank/Total ratio of 2.3%. Sensitivity, expressed as the mean minimum detectable dose, was 40 pg/tube, equivalent to 56 pg/ml plasma. Intra-assay variation coefficients were 6.5%, 3.8% and 6.8%, respectively, at B/Bo levels of 0.8, 0.6 and 0.4 of the standard curve. At B/Bo equal to 0.5, the intra-assay variation coefficient was 20.9%. Replicates of 14 plasma samples showed a correlation coefficient of r 0.99, (p< 0.05). Parallelism between the curve obtained with different volumes of an extract with a high βLPH value and the standard curve was found. The method was controlled biologically by the presence of correlation between the plasma βLPH levels and determined pathological states and with clinical functional studies. Twenty seven normal individuals, 10 patients with Cushing's disease to a tumor of the hypophysis, 4 patients with Cushing syndrome due to an adrenal tumor, 10 patients Addison disease, and 8 patients with hypopituitarism were studied. (author). 119 refs., 28 figs., 2 tabs

  1. Malware Normalization

    OpenAIRE

    Christodorescu, Mihai; Kinder, Johannes; Jha, Somesh; Katzenbeisser, Stefan; Veith, Helmut

    2005-01-01

    Malware is code designed for a malicious purpose, such as obtaining root privilege on a host. A malware detector identifies malware and thus prevents it from adversely affecting a host. In order to evade detection by malware detectors, malware writers use various obfuscation techniques to transform their malware. There is strong evidence that commercial malware detectors are susceptible to these evasion tactics. In this paper, we describe the design and implementation of a malware normalizer ...

  2. A perspective on extracellular vesicles proteomics

    Science.gov (United States)

    Rosa-Fernandes, Livia; Rocha, Victória Bombarda; Carregari, Victor Corasolla; Urbani, Andrea; Palmisano, Giuseppe

    2017-11-01

    Increasing attention has been given to secreted extracellular vesicles (EVs) in the past decades, especially in the portrayal of their molecular cargo and role as messengers in both homeostasis and pathophysiological conditions. This review presents the state-of-the-art proteomic technologies to identify and quantify EVs proteins along with their PTMs, interacting partners and structural details. The rapid growth of mass spectrometry-based analytical strategies for protein sequencing, PTMs and structural characterization has improved the level of molecular details that can be achieve from limited amount of EVs isolated from different biological sources. Here we will provide a perspective view on the achievements and challenges on EVs proteome characterization using mass spectrometry. A detailed bioinformatics approach will help us to picture the molecular fingerprint of EVs and understand better their pathophysiological function.

  3. An immunofluorescence assay for extracellular matrix components highlights the role of epithelial cells in producing a stable, fibrillar extracellular matrix

    Directory of Open Access Journals (Sweden)

    Omar S. Qureshi

    2017-10-01

    Full Text Available Activated fibroblasts are considered major drivers of fibrotic disease progression through the production of excessive extracellular matrix (ECM in response to signals from damaged epithelial and inflammatory cells. Nevertheless, epithelial cells are capable of expressing components of the ECM, cross-linking enzymes that increase its stability and are sensitive to factors involved in the early stages of fibrosis. We therefore wanted to test the hypothesis that epithelial cells can deposit ECM in response to stimulation in a comparable manner to fibroblasts. We performed immunofluorescence analysis of components of stable, mature extracellular matrix produced by primary human renal proximal tubular epithelial cells and renal fibroblasts in response to cytokine stimulation. Whilst fibroblasts produced a higher basal level of extracellular matrix components, epithelial cells were able to deposit significant levels of fibronectin, collagen I, III and IV in response to cytokine stimulation. In response to hypoxia, epithelial cells showed an increase in collagen IV deposition but not in response to the acute stress stimuli aristolochic acid or hydrogen peroxide. When epithelial cells were in co-culture with fibroblasts we observed significant increases in the level of matrix deposition which could be reduced by transforming growth factor beta (TGF-β blockade. Our results highlight the role of epithelial cells acting as efficient producers of stable extracellular matrix which could contribute to renal tubule thickening in fibrosis.

  4. Analysis of extracellular RNA by digital PCR

    Directory of Open Access Journals (Sweden)

    Kenji eTakahashi

    2014-06-01

    Full Text Available The transfer of extracellular RNA is emerging as an important mechanism for intracellular communication. The ability for the transfer of functionally active RNA molecules from one cell to another within vesicles such as exosomes enables a cell to modulate cellular signaling and biological processes within recipient cells. The study of extracellular RNA requires sensitive methods for the detection of these molecules. In this methods article, we will describe protocols for the detection of such extracellular RNA using sensitive detection technologies such as digital PCR. These protocols should be valuable to researchers interested in the role and contribution of extracellular RNA to tumor cell biology.

  5. Extracellular Molecules Involved in Cancer Cell Invasion

    International Nuclear Information System (INIS)

    Stivarou, Theodora; Patsavoudi, Evangelia

    2015-01-01

    Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion

  6. Extracellular Molecules Involved in Cancer Cell Invasion

    Directory of Open Access Journals (Sweden)

    Theodora Stivarou

    2015-01-01

    Full Text Available Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  7. A genomic point mutation in the extracellular domain of the thyrotropin receptor in patients with Graves` ophthalmopathy

    Energy Technology Data Exchange (ETDEWEB)

    Bahn, R.S.; Dutton, C.M.; Heufelder, A.E.; Sarkar, G. [Mayo Clinic/Foundation, Rochester, MN (United States)]|[Ludwig-Maximilians-Universitat, Munich (Germany)

    1994-02-01

    Orbital and pretibial fibroblasts are targets of autoimmune attack in Graves` ophthalmopathy (GO) and pretibial dermopathy (PTD). The fibroblast autoantigen involved in these peripheral manifestations of Graves` disease and the reason for the association of GO and PTD with hyperthyroidism are unknown. RNA encoding the full-length extracellular domain of the TSH receptor has been demonstrated in orbital and dermal fibroblasts from patients with GO and normal subjects, suggesting a possible antigenic link between fibroblasts and thyrocytes. RNA was isolated from cultured orbital, pretibial, and abdominal fibroblasts obtained from patients with severe GO (n = 22) and normal subjects (n = 5). RNA was reverse transcribed, and the resulting cDNA was amplified by the polymerase chain reaction, using primers spanning overlapping regions of the entire extracellular domain of the TSH receptor. Nucleotide sequence analysis showed an A for C substitution in the first position of codon 52 in 2 of the patients, both of whom had GO, PTD, and acropachy. Genomic DNA isolated from the 2 affected patients, and not from an additional 12 normal subjects, revealed the codon 52 mutation by direct sequencing and AciI restriction enzyme digestions. In conclusion, the authors have demonstrated the presence of a genomic point mutation, leading to a threonine for proline amino acid shift in the predicted peptide, in the extracellular domain of the TSH receptor in two patients with severe GO, PTD, acropachy, and high thyroid-stimulating immunoglobulin levels. RNA encoding this mutant product was demonstrated in the fibroblasts of these patients. They suggest that the TSH receptor may be an important fibroblast autoantigen in GO and PTD, and that this mutant form of the receptor may have unique immunogenic properties. 28 refs., 3 figs., 2 tabs.

  8. Neutrophil extracellular traps promote deep vein thrombosis in mice

    Science.gov (United States)

    Brill, A.; Fuchs, T.A.; Savchenko, A.S.; Thomas, G.M.; Martinod, K.; De Meyer, S.F.; Bhandari, A.A.; Wagner, D.D.

    2011-01-01

    Summary Background Upon activation, neutrophils can release nuclear material known as neutrophil extracellular traps (NETs), which were initially described as a part of antimicrobial defense. Extracellular chromatin was recently reported to be pro-thrombotic in vitro and to accumulate in plasma and thrombi of baboons with experimental deep vein thrombosis (DVT). Objective To explore the source and role of extracellular chromatin in DVT. Methods We used an established murine model of DVT induced by flow restriction (stenosis) in the inferior vena cava (IVC). Results We demonstrate that the levels of extracellular DNA increase in plasma after 6 h IVC stenosis, compared to sham-operated mice. Immunohistochemical staining revealed the presence of Gr-1-positive neutrophils in both red (RBC-rich) and white (platelet-rich) parts of thrombi. Citrullinated histone H3 (CitH3), an element of NETs’ structure, was present only in the red part of thrombi and was frequently associated with the Gr-1 antigen. Immunofluorescent staining of thrombi showed proximity of extracellular CitH3 and von Willebrand factor (VWF), a platelet adhesion molecule crucial for thrombus development in this model. Infusion of Deoxyribonuclease 1 (DNase 1) protected mice from DVT after 6 h and also 48 h IVC stenosis. Infusion of an unfractionated mixture of calf thymus histones increased plasma VWF and promoted DVT early after stenosis application. Conclusions Extracellular chromatin, likely originating from neutrophils, is a structural part of a venous thrombus and both the DNA scaffold and histones appear to contribute to the pathogenesis of DVT in mice. NETs may provide new targets for DVT drug development. PMID:22044575

  9. Normal accidents

    International Nuclear Information System (INIS)

    Perrow, C.

    1989-01-01

    The author has chosen numerous concrete examples to illustrate the hazardousness inherent in high-risk technologies. Starting with the TMI reactor accident in 1979, he shows that it is not only the nuclear energy sector that bears the risk of 'normal accidents', but also quite a number of other technologies and industrial sectors, or research fields. The author refers to the petrochemical industry, shipping, air traffic, large dams, mining activities, and genetic engineering, showing that due to the complexity of the systems and their manifold, rapidly interacting processes, accidents happen that cannot be thoroughly calculated, and hence are unavoidable. (orig./HP) [de

  10. Tlx acts as a proangiogenic switch by regulating extracellular assembly of fibronectin matrices in retinal astrocytes.

    Science.gov (United States)

    Uemura, Akiyoshi; Kusuhara, Sentaro; Wiegand, Stanley J; Yu, Ruth T; Nishikawa, Shin-ichi

    2006-02-01

    In response to hypoxia, hypoxia-inducible factors act as the primary proangiogenic triggers by regulating transcription levels of target genes, including VEGF. However, little is known about the specific factors that control other components of the angiogenic process, particularly formation of matrix scaffolds that promote adhesion and migration of endothelial cells. We show that in the postnatal mouse retina, the orphan nuclear receptor tailless (Tlx) is strongly expressed in the proangiogenic astrocytes, which secrete VEGF and fibronectin. Tlx expression by retinal astrocytes is controlled by oxygen concentration and rapidly downregulated upon contact with blood vessels. In mice null for Tlx, retinal astrocytes maintain VEGF expression; however, the extracellular assembly of fibronectin matrices by astrocytes is severely impaired, leading to defective scaffold formation and a complete failure of normal retinal vascular development. This work identifies Tlx as an essential component of the molecular network involved in the hypoxia-inducible proangiogenic switch in retinal astrocytes.

  11. Proteoglycans in Leiomyoma and Normal Myometrium

    Science.gov (United States)

    Barker, Nichole M.; Carrino, David A.; Caplan, Arnold I.; Hurd, William W.; Liu, James H.; Tan, Huiqing; Mesiano, Sam

    2015-01-01

    Uterine leiomyoma are a common benign pelvic tumors composed of modified smooth muscle cells and a large amount of extracellular matrix (ECM). The proteoglycan composition of the leiomyoma ECM is thought to affect pathophysiology of the disease. To test this hypothesis, we examined the abundance (by immunoblotting) and expression (by quantitative real-time polymerase chain reaction) of the proteoglycans biglycan, decorin, and versican in leiomyoma and normal myometrium and determined whether expression is affected by steroid hormones and menstrual phase. Leiomyoma and normal myometrium were collected from women (n = 17) undergoing hysterectomy or myomectomy. In vitro studies were performed on immortalized leiomyoma (UtLM) and normal myometrial (hTERT-HM) cells with and without exposure to estradiol and progesterone. In leiomyoma tissue, abundance of decorin messenger RNA (mRNA) and protein were 2.6-fold and 1.4-fold lower, respectively, compared with normal myometrium. Abundance of versican mRNA was not different between matched samples, whereas versican protein was increased 1.8-fold in leiomyoma compared with myometrium. Decorin mRNA was 2.4-fold lower in secretory phase leiomyoma compared with proliferative phase tissue. In UtLM cells, progesterone decreased the abundance of decorin mRNA by 1.3-fold. Lower decorin expression in leiomyoma compared with myometrium may contribute to disease growth and progression. As decorin inhibits the activity of specific growth factors, its reduced level in the leiomyoma cell microenvironment may promote cell proliferation and ECM deposition. Our data suggest that decorin expression in leiomyoma is inhibited by progesterone, which may be a mechanism by which the ovarian steroids affect leiomyoma growth and disease progression. PMID:26423601

  12. New extracellular resistance mechanism for cisplatin.

    Science.gov (United States)

    Centerwall, Corey R; Kerwood, Deborah J; Goodisman, Jerry; Toms, Bonnie B; Dabrowiak, James C

    2008-01-01

    The HSQC NMR spectrum of 15N-cisplatin in cell growth media shows resonances corresponding to the monocarbonato complex, cis-[Pt(NH3)2(CO3)Cl](-), 4, and the dicarbonato complex, cis-[Pt(NH3)2(CO3)2](-2), 5, in addition to cisplatin itself, cis-[Pt(NH3)2Cl2], 1. The presence of Jurkat cells reduces the amount of detectable carbonato species by (2.8+/-0.7) fmol per cell and has little effect on species 1. Jurkat cells made resistant to cisplatin reduce the amount of detectable carbonato species by (7.9+/-5.6) fmol per cell and also reduce the amount of 1 by (3.4+/-0.9) fmol per cell. The amount of detectable carbonato species is also reduced by addition of the drug to medium that has previously been in contact with normal Jurkat cells (cells removed); the reduction is greater when drug is added to medium previously in contact with resistant Jurkat cells (cells removed). This shows that the platinum species are modified by a cell-produced substance that is released to the medium. Since the modified species have been shown not to enter or bind to cells, and since resistant cells modify more than non-resistant cells, the modification constitutes a new extracellular mechanism for cisplatin resistance which merits further attention.

  13. The International Society for Extracellular Vesicles launches the first massive open online course on extracellular vesicles

    OpenAIRE

    L?sser, Cecilia; Th?ry, Clotilde; Buz?s, Edit I.; Mathivanan, Suresh; Zhao, Weian; Gho, Yong Song; L?tvall, Jan

    2016-01-01

    The International Society for Extracellular Vesicles (ISEV) has organised its first educational online course for students and beginners in the field of extracellular vesicles (EVs). This course, “Basics of Extracellular Vesicles,” uses recorded lectures from experts in the field and will be open for an unlimited number of participants. The course is divided into 5 modules and can be accessed at www.coursera.org/learn/extracellular-vesicles. The first module is an introduction to the field co...

  14. Reconstructing Normality

    DEFF Research Database (Denmark)

    Gildberg, Frederik Alkier; Bradley, Stephen K.; Fristed, Peter Billeskov

    2012-01-01

    Forensic psychiatry is an area of priority for the Danish Government. As the field expands, this calls for increased knowledge about mental health nursing practice, as this is part of the forensic psychiatry treatment offered. However, only sparse research exists in this area. The aim of this study...... was to investigate the characteristics of forensic mental health nursing staff interaction with forensic mental health inpatients and to explore how staff give meaning to these interactions. The project included 32 forensic mental health staff members, with over 307 hours of participant observations, 48 informal....... The intention is to establish a trusting relationship to form behaviour and perceptual-corrective care, which is characterized by staff's endeavours to change, halt, or support the patient's behaviour or perception in relation to staff's perception of normality. The intention is to support and teach the patient...

  15. Pursuing Normality

    DEFF Research Database (Denmark)

    Madsen, Louise Sofia; Handberg, Charlotte

    2018-01-01

    implying an influence on whether to participate in cancer survivorship care programs. Because of "pursuing normality," 8 of 9 participants opted out of cancer survivorship care programming due to prospects of "being cured" and perceptions of cancer survivorship care as "a continuation of the disease......BACKGROUND: The present study explored the reflections on cancer survivorship care of lymphoma survivors in active treatment. Lymphoma survivors have survivorship care needs, yet their participation in cancer survivorship care programs is still reported as low. OBJECTIVE: The aim of this study...... was to understand the reflections on cancer survivorship care of lymphoma survivors to aid the future planning of cancer survivorship care and overcome barriers to participation. METHODS: Data were generated in a hematological ward during 4 months of ethnographic fieldwork, including participant observation and 46...

  16. Extracellular matrix alterations in human corneas with bullous keratopathy

    DEFF Research Database (Denmark)

    Ljubimov, A V; Burgeson, R E; Butkowski, R J

    1996-01-01

    PURPOSE. To uncover abnormalities of extracellular matrix (ECM) distribution in human corneas with pseudophakic and aphakic bullous keratopathy (PBK/ABK). METHODS. Indirect immunofluorescence with antibodies to 27 ECM components was used on frozen sections of 14 normal and 20 PBK/ABK corneas...... in some cases, correlated with decreased visual acuity. In normal central corneas, tenascin was never found. Other major ECM abnormalities in PBK/ABK corneas compared to normals included: discontinuous epithelial BM straining for laminin-1 (alpha 1 beta 1 gamma 1), entactin/nidogen and fibronectin......; accumulation of fibronectin and alpha 1-alpha 2 type IV collagen on the endothelial face of the Descemet's membrane; and abnormal deposition of stromal ECM (tenascin, fibronectin, decorin, types I, III, V, VI, VIII, XII, XIV collagen) and BM components (type IV, collagen, perlecan, bamacan, laminin-1, entactin...

  17. Clinical significance of preoperative serum albumin level for prognosis in surgically resected patients with non-small cell lung cancer: Comparative study of normal lung, emphysema, and pulmonary fibrosis.

    Science.gov (United States)

    Miura, Kentaro; Hamanaka, Kazutoshi; Koizumi, Tomonobu; Kitaguchi, Yoshiaki; Terada, Yukihiro; Nakamura, Daisuke; Kumeda, Hirotaka; Agatsuma, Hiroyuki; Hyogotani, Akira; Kawakami, Satoshi; Yoshizawa, Akihiko; Asaka, Shiho; Ito, Ken-Ichi

    2017-09-01

    This study was performed to clarify whether preoperative serum albumin level is related to the prognosis of non-small cell lung cancer patients undergoing surgical resection, and the relationships between serum albumin level and clinicopathological characteristics of lung cancer patients with emphysema or pulmonary fibrosis. We retrospectively evaluated 556 patients that underwent surgical resection for non-small cell lung cancer. The correlation between preoperative serum albumin level and survival was evaluated. Patients were divided into three groups according to the findings on chest high-resolution computed tomography (normal lung, emphysema, and pulmonary fibrosis), and the relationships between serum albumin level and clinicopathological characteristics, including prognosis, were evaluated. The cut-off value of serum albumin level was set at 4.2g/dL. Patients with low albumin levels (albumin emphysema group (n=48) and pulmonary fibrosis group (n=45) were significantly lower than that in the normal lung group (n=463) (p=0.009 and pulmonary fibrosis groups, but not in the emphysema group. Preoperative serum albumin level was an important prognostic factor for overall survival and recurrence-free survival in patients with resected non-small cell lung cancer. Divided into normal lung, emphysema, and pulmonary fibrosis groups, serum albumin level showed no influence only in patients in the emphysema group. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Extracellular matrix components direct porcine muscle stem cell behavior

    International Nuclear Information System (INIS)

    Wilschut, Karlijn J.; Haagsman, Henk P.; Roelen, Bernard A.J.

    2010-01-01

    In muscle tissue, extracellular matrix proteins, together with the vasculature system, muscle-residence cells and muscle fibers, create the niche for muscle stem cells. The niche is important in controlling proliferation and directing differentiation of muscle stem cells to sustain muscle tissue. Mimicking the extracellular muscle environment improves tools exploring the behavior of primary muscle cells. Optimizing cell culture conditions to maintain muscle commitment is important in stem cell-based studies concerning toxicology screening, ex vivo skeletal muscle tissue engineering and in the enhancement of clinical efficiency. We used the muscle extracellular matrix proteins collagen type I, fibronectin, laminin, and also gelatin and Matrigel as surface coatings of tissue culture plastic to resemble the muscle extracellular matrix. Several important factors that determine myogenic commitment of the primary muscle cells were characterized by quantitative real-time RT-PCR and immunofluorescence. Adhesion of high PAX7 expressing satellite cells was improved if the cells were cultured on fibronectin or laminin coatings. Cells cultured on Matrigel and laminin coatings showed dominant integrin expression levels and exhibited an activated Wnt pathway. Under these conditions both stem cell proliferation and myogenic differentiation capacity were superior if compared to cells cultured on collagen type I, fibronectin and gelatin. In conclusion, Matrigel and laminin are the preferred coatings to sustain the proliferation and myogenic differentiation capacity of the primary porcine muscle stem cells, when cells are removed from their natural environment for in vitro culture.

  19. Extracellular matrix components direct porcine muscle stem cell behavior

    Energy Technology Data Exchange (ETDEWEB)

    Wilschut, Karlijn J. [Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht (Netherlands); Haagsman, Henk P. [Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht (Netherlands); Roelen, Bernard A.J., E-mail: b.a.j.roelen@uu.nl [Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht (Netherlands)

    2010-02-01

    In muscle tissue, extracellular matrix proteins, together with the vasculature system, muscle-residence cells and muscle fibers, create the niche for muscle stem cells. The niche is important in controlling proliferation and directing differentiation of muscle stem cells to sustain muscle tissue. Mimicking the extracellular muscle environment improves tools exploring the behavior of primary muscle cells. Optimizing cell culture conditions to maintain muscle commitment is important in stem cell-based studies concerning toxicology screening, ex vivo skeletal muscle tissue engineering and in the enhancement of clinical efficiency. We used the muscle extracellular matrix proteins collagen type I, fibronectin, laminin, and also gelatin and Matrigel as surface coatings of tissue culture plastic to resemble the muscle extracellular matrix. Several important factors that determine myogenic commitment of the primary muscle cells were characterized by quantitative real-time RT-PCR and immunofluorescence. Adhesion of high PAX7 expressing satellite cells was improved if the cells were cultured on fibronectin or laminin coatings. Cells cultured on Matrigel and laminin coatings showed dominant integrin expression levels and exhibited an activated Wnt pathway. Under these conditions both stem cell proliferation and myogenic differentiation capacity were superior if compared to cells cultured on collagen type I, fibronectin and gelatin. In conclusion, Matrigel and laminin are the preferred coatings to sustain the proliferation and myogenic differentiation capacity of the primary porcine muscle stem cells, when cells are removed from their natural environment for in vitro culture.

  20. Normal-Mode Analysis of Circular DNA at the Base-Pair Level. 2. Large-Scale Configurational Transformation of a Naturally Curved Molecule.

    Science.gov (United States)

    Matsumoto, Atsushi; Tobias, Irwin; Olson, Wilma K

    2005-01-01

    Fine structural and energetic details embedded in the DNA base sequence, such as intrinsic curvature, are important to the packaging and processing of the genetic material. Here we investigate the internal dynamics of a 200 bp closed circular molecule with natural curvature using a newly developed normal-mode treatment of DNA in terms of neighboring base-pair "step" parameters. The intrinsic curvature of the DNA is described by a 10 bp repeating pattern of bending distortions at successive base-pair steps. We vary the degree of intrinsic curvature and the superhelical stress on the molecule and consider the normal-mode fluctuations of both the circle and the stable figure-8 configuration under conditions where the energies of the two states are similar. To extract the properties due solely to curvature, we ignore other important features of the double helix, such as the extensibility of the chain, the anisotropy of local bending, and the coupling of step parameters. We compare the computed normal modes of the curved DNA model with the corresponding dynamical features of a covalently closed duplex of the same chain length constructed from naturally straight DNA and with the theoretically predicted dynamical properties of a naturally circular, inextensible elastic rod, i.e., an O-ring. The cyclic molecules with intrinsic curvature are found to be more deformable under superhelical stress than rings formed from naturally straight DNA. As superhelical stress is accumulated in the DNA, the frequency, i.e., energy, of the dominant bending mode decreases in value, and if the imposed stress is sufficiently large, a global configurational rearrangement of the circle to the figure-8 form takes place. We combine energy minimization with normal-mode calculations of the two states to decipher the configurational pathway between the two states. We also describe and make use of a general analytical treatment of the thermal fluctuations of an elastic rod to characterize the

  1. Extracellular DNA metabolism in Haloferax volcanii

    Directory of Open Access Journals (Sweden)

    Scott eChimileski

    2014-02-01

    Full Text Available Extracellular DNA is found in all environments and is a dynamic component of the micro-bial ecosystem. Microbial cells produce and interact with extracellular DNA through many endogenous mechanisms. Extracellular DNA is processed and internalized for use as genetic information and as a major source of macronutrients, and plays several key roles within prokaryotic biofilms. Hypersaline sites contain some of the highest extracellular DNA con-centrations measured in nature–a potential rich source of carbon, nitrogen and phosphorus for halophilic microorganisms. We conducted DNA growth studies for the halophilic archaeon Haloferax volcanii DS2 and show that this model Halobacteriales strain is capable of using exogenous double-stranded DNA as a nutrient. Further experiments with varying medium composition, DNA concentration and DNA types revealed that DNA is utilized primarily as a phosphorus source, that growth on DNA is concentration-dependent and that DNA isolated from different sources is metabolized selectively, with a bias against highly divergent methylated DNA sources. Additionally, fluorescence microscopy experiments showed that labeled DNA colocalized with Haloferax volcanii cells. The gene Hvo_1477 was also identified using a comparative genomic approach as a factor likely to be involved in extracellular DNA processing at the cell surface, and deletion of Hvo_1477 created an H. volcanii strain deficient in its ability to grow on extracellular DNA. Widespread distribution of Hvo_1477 homologs in archaea suggests metabolism of extracellular DNA may be of broad ecological and physiological relevance in this domain of life.

  2. Effect of extracellular calcium chloride on sporangiospore-yeast ...

    African Journals Online (AJOL)

    To examine this model further, this study evaluated the ability of sporangiospores of Rhizopus stolonifer to undergo morphogenetic transformation in the presence of different levels of extracellular calcium (0.0, 0.20, 0.25, 0.50, 1.0, 1.5 and 1.8 mM). It was found that calcium supported yeast induction and proliferation to ...

  3. Bacterial binding to extracellular proteins - in vitro adhesion

    DEFF Research Database (Denmark)

    Schou, C.; Fiehn, N.-E.

    1999-01-01

    Viridans streptococci, bacterial adherence, extracellular matrix proteins, surface receptors, endocarditis......Viridans streptococci, bacterial adherence, extracellular matrix proteins, surface receptors, endocarditis...

  4. Normal Morning Melanin-Concentrating Hormone Levels and No Association with Rapid Eye Movement or Non-Rapid Eye Movement Sleep Parameters in Narcolepsy Type 1 and Type 2

    DEFF Research Database (Denmark)

    Schrölkamp, Maren; Jennum, Poul J; Gammeltoft, Steen

    2017-01-01

    in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep regulation. Hypocretin neurons reciprocally interact with MCH neurons. We hypothesized that altered MCH secretion contributes to the symptoms and sleep abnormalities of narcolepsy and that this is reflected in morning cerebrospinal fluid...... MCH levels. CONCLUSIONS: Our study shows that MCH levels in CSF collected in the morning are normal in narcolepsy and not associated with the clinical symptoms, REM sleep abnormalities, nor number of muscle movements during REM or NREM sleep of the patients. We conclude that morning lumbar CSF MCH......STUDY OBJECTIVES: Other than hypocretin-1 (HCRT-1) deficiency in narcolepsy type 1 (NT1), the neurochemical imbalance of NT1 and narcolepsy type 2 (NT2) with normal HCRT-1 levels is largely unknown. The neuropeptide melanin-concentrating hormone (MCH) is mainly secreted during sleep and is involved...

  5. Detection of extracellular enzymatic activity in microorganisms ...

    African Journals Online (AJOL)

    Detection of extracellular enzymatic activity in microorganisms isolated from waste vegetable oil contaminated soil using plate methodologies. Eugenia G. Ortiz Lechuga, Isela Quintero Zapata, Katiushka Arévalo Niño ...

  6. Purification and characterization of extracellular amylolytic enzyme ...

    African Journals Online (AJOL)

    DOSS

    2012-10-16

    Oct 16, 2012 ... Available online at http://www.academicjournals.org/AJB ... characterization of extracellular amylases from four ... Somogyi-Nelson's method (Nelson, 1944; Somogyi, 1952). ... The mycelia dry weight of currently studied four.

  7. Neutrophil Extracellular Traps in Ulcerative Colitis

    DEFF Research Database (Denmark)

    Bjerg Bennike, Tue; Carlsen, Thomas Gelsing; Ellingsen, Torkell

    2015-01-01

    microscopy and confocal microscopy. RESULTS: We identified and quantified 5711 different proteins with proteomics. The abundance of the proteins calprotectin and lactotransferrin in the tissue correlated with the degree of tissue inflammation as determined by histology. However, fecal calprotectin did...... not correlate. Forty-six proteins were measured with a statistically significant differences in abundances between the UC colon tissue and controls. Eleven of the proteins with increased abundances in the UC biopsies were associated with neutrophils and neutrophil extracellular traps. The findings were...... validated by microscopy, where an increased abundance of neutrophils and the presence of neutrophil extracellular traps by extracellular DNA present in the UC colon tissue were confirmed. CONCLUSIONS: Neutrophils, induced neutrophil extracellular traps, and several proteins that play a part in innate...

  8. Increased levels of specific leukocyte- and platelet-derived substances during normal anti-tetanus antibody synthesis in patients with inactive Crohn disease

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Mortensen, T; Holten-Andersen, M

    2001-01-01

    , vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinases-1 (TIMP-1), plasminogen activator inhibitor type-1 (PAI-1) and myeloperoxidase (MPO) were determined in serum or plasma obtained on the same days. RESULTS: After inoculation anti-tetanus antibody levels were equally raised...... immunization in patients with Crohn disease and the subsequent release of various inflammatory mediators and growth factors in blood. METHODS: Ten patients with inactive disease and no concurrent medication and 12 age-and gender-matched healthy volunteers with anti-tetanus antibody levels less than 0.1 IU...... range and IL-6, TNF-alpha, MPO and histamine levels were unchanged in patients and volunteers during the study period. The levels of VEGF, TIMP-1 and PAI-1 were unchanged in the healthy volunteers during the study period, but were significantly (P

  9. Serum Levels Of Free And Total Insulin-Like Growth Factor (IGF)-1 And IGF Binding Protein-3 In Normal And Growth Hormone Deficient Children

    International Nuclear Information System (INIS)

    Shousha, M.A.; Soliman, S.E.T.; Hafez, M.H.

    2006-01-01

    Serum levels of total insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) reflect the endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening growth hormone deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-1 circulates in its free form, which is believed to be the biologically active form. Serum levels of free IGF-1, total IGF-I and IGFBP-3 were measured in 144 healthy children (72 boys and 72 girls, aged from 0 to 16 years) and in 12 pre-pubertal GH deficient (GHD) children to study the correlation between the age and free IGF-1, total IGF-1 and IGFBP-3 levels. In healthy subjects (both sexes), serum free IGF-1, total IGF-1 and IGFBP-3 levels were low in infancy, increasing during puberty and declining thereafter. Free IGF-1 in serum occupied about 0.97-1.45 % of the total IGF-1 values, and the ratios of free IGF-1 to total IGF-1 were significantly increased in the pubertal age groups than in the pre-pubertal age groups. Serum levels of free IGF-1 showed significant positive correlation with those of total IGF-I and IGFBP-3. Serum free IGF-1, total IGF-1 and IGFBP-3 levels in patients with GHD were decreased significantly with increasing the degree of hypopituitarism. These observations suggest that the increase in serum free IGF-1 level during puberty was caused by a dramatic increase in total IGF-1 rather than IGFBP-3. Also, high levels of these hormones may play an important role in pubertal growth spurt and may become a useful tool for diagnosing GHD and predicting growth response to long term GH therapy

  10. Serum levels of free and total insulin-link growth factor (IGF)-1 and (IGF) binding protein-3 in normal and growth hormone deficient children

    International Nuclear Information System (INIS)

    Shousha, M.A.; Soliman, S.E.T.; Hafez, H.M.

    2008-01-01

    Serum levels of total insulin-like growth factor- 1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) reflect endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening GH deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-1 circulates in its free form, which is believed to be the biologically active form. Serum levels of free IGF-1, total IGF-I and IGFBP-3 were measured in 144 healthy children (72 boys and 72 girls, aged from 0 to 16 years) and in 12 prepubertal GH. deficient (GHD) children to study correlation between the age and free IGF-1, total IGF-1 and IGFBP-3 levels. In healthy subjects (both sexes), serum free IGF-1, total IGF-1 and IGFBP-3 levels were low in infancy, increasing during puberty and declining thereafter. Free IGF-1 in serum occupied about 0.97. 1.45 % of the total IGF-1 values, and the ratios of free IGF-1 to total IGF-1 were significantly increased in the pubertal age groups than in the prepubertal age groups. Serum levels of free IGF-1 showed significant positive correlation with those of total IGF-I and IGFBP-3. Serum free IGF-1, total IGF-1 and IGFBP-3 levels in patients with GHD decreased significantly with increasing degree of hypopituitarism. These observations suggest that the increase in serum free IGF-1 level during puberty was caused by a dramatic increase in total IGF-1 rather than IGFBP-3. Also, high levels of these hormones may play an important role in pubertal growth spurt and may become a useful tool for diagnosing GHD and predicting growth response to long term GH therapy

  11. Serum levels at moment of breeding of triiodothyronine (T3), thyroxine (T4), and progesterone in Saanen goats females during normal and induced heat and testosterone in 12 Saanen goats males

    International Nuclear Information System (INIS)

    Prestes, Nereu C.; Vulcano, Luiz C.; Mamprim, Maria J.; Oba, Eunice

    1996-01-01

    The aim of this experiment was to measure the level of triiodothyronine(T 3 ), thyroxine(T 4 ) and progesterone in the serum of females Saanen goats. The progesterone levels were: 0.59 and 0.79 ng/μl considering breeding during normal and induced heat respectively. The T 3 values were: 192.8 and 251.32 ng/dl while T 4 values were: 36.38 and 31.68 ng/dl in the same condition above. The average testosterone level at the moment of breeding in the serum of 12 males was 1.38 pg/ml. (author)

  12. Functional transferred DNA within extracellular vesicles

    International Nuclear Information System (INIS)

    Cai, Jin; Wu, Gengze; Jose, Pedro A.; Zeng, Chunyu

    2016-01-01

    Extracellular vesicles (EVs) are small membrane vesicles including exosomes and shedding vesicles that mediated a cell-to-cell communication. EVs are released from almost all cell types under both physiological and pathological conditions and incorporate nuclear and cytoplasmic molecules for intercellular delivery. Besides protein, mRNA, and microRNA of these molecules, as recent studies show, specific DNA are prominently packaged into EVs. It appears likely that some of exosomes or shedding vesicles, bearing nuclear molecules are released upon bubble-like blebs. Specific interaction of EVs with susceptible recipients performs the uptake of EVs into the target cells, discharging their cargo including nuclear and cytoplasmic macromolecules into the cytosol. These findings expand the nucleic acid content of EVs to include increased levels of specific DNA. Thus, EVs contain a repertoire of genetic information available for horizontal gene transfer and potential use as blood biomarkers for cancer and atherosclerosis. In this review, the focus is on the characteristics, biological functions, and roles in diseases of DNA within EVs. - Highlights: • This review is focused on the DNA within EVs including its characteristics, biological functions, and roles in diseases. • It is clear that DNA within EVs might have important physiological and pathological roles in various diseases. • Knowledge in this area may provides us alternative methods for disease diagnosis or therapy in the future.

  13. Functional transferred DNA within extracellular vesicles

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Jin [Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China); Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province (China); Wu, Gengze [Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China); Jose, Pedro A. [Division of Nephrology, Department of Medicine and Physiology, University of Maryland, School of Medicine, Baltimore, MD 21201 (United States); Zeng, Chunyu, E-mail: Chunyuzeng01@163.com [Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China)

    2016-11-15

    Extracellular vesicles (EVs) are small membrane vesicles including exosomes and shedding vesicles that mediated a cell-to-cell communication. EVs are released from almost all cell types under both physiological and pathological conditions and incorporate nuclear and cytoplasmic molecules for intercellular delivery. Besides protein, mRNA, and microRNA of these molecules, as recent studies show, specific DNA are prominently packaged into EVs. It appears likely that some of exosomes or shedding vesicles, bearing nuclear molecules are released upon bubble-like blebs. Specific interaction of EVs with susceptible recipients performs the uptake of EVs into the target cells, discharging their cargo including nuclear and cytoplasmic macromolecules into the cytosol. These findings expand the nucleic acid content of EVs to include increased levels of specific DNA. Thus, EVs contain a repertoire of genetic information available for horizontal gene transfer and potential use as blood biomarkers for cancer and atherosclerosis. In this review, the focus is on the characteristics, biological functions, and roles in diseases of DNA within EVs. - Highlights: • This review is focused on the DNA within EVs including its characteristics, biological functions, and roles in diseases. • It is clear that DNA within EVs might have important physiological and pathological roles in various diseases. • Knowledge in this area may provides us alternative methods for disease diagnosis or therapy in the future.

  14. Sources of extracellular tau and its signaling.

    Science.gov (United States)

    Avila, Jesús; Simón, Diana; Díaz-Hernández, Miguel; Pintor, Jesús; Hernández, Félix

    2014-01-01

    The pathology associated with tau protein, tauopathy, has been recently analyzed in different disorders, leading to the suggestion that intracellular and extracellular tau may itself be the principal agent in the transmission and spreading of tauopathies. Tau pathology is based on an increase in the amount of tau, an increase in phosphorylated tau, and/or an increase in aggregated tau. Indeed, phosphorylated tau protein is the main component of tau aggregates, such as the neurofibrillary tangles present in the brain of Alzheimer's disease patients. It has been suggested that intracellular tau could be toxic to neurons in its phosphorylated and/or aggregated form. However, extracellular tau could also damage neurons and since neuronal death is widespread in Alzheimer's disease, mainly among cholinergic neurons, these cells may represent a possible source of extracellular tau. However, other sources of extracellular tau have been proposed that are independent of cell death. In addition, several ways have been proposed for cells to interact with, transmit, and spread extracellular tau, and to transduce signals mediated by this tau. In this work, we will discuss the role of extracellular tau in the spreading of the tau pathology.

  15. Transcriptome of extracellular vesicles released by hepatocytes.

    Directory of Open Access Journals (Sweden)

    Felix Royo

    Full Text Available The discovery that the cells communicate through emission of vesicles has opened new opportunities for better understanding of physiological and pathological mechanisms. This discovery also provides a novel source for non-invasive disease biomarker research. Our group has previously reported that hepatocytes release extracellular vesicles with protein content reflecting the cell-type of origin. Here, we show that the extracellular vesicles released by hepatocytes also carry RNA. We report the messenger RNA composition of extracellular vesicles released in two non-tumoral hepatic models: primary culture of rat hepatocytes and a progenitor cell line obtained from a mouse foetal liver. We describe different subpopulations of extracellular vesicles with different densities and protein and RNA content. We also show that the RNA cargo of extracellular vesicles released by primary hepatocytes can be transferred to rat liver stellate-like cells and promote their activation. Finally, we provide in vitro and in vivo evidence that liver-damaging drugs galactosamine, acetaminophen, and diclofenac modify the RNA content of these vesicles. To summarize, we show that the extracellular vesicles secreted by hepatocytes contain various RNAs. These vesicles, likely to be involved in the activation of stellate cells, might become a new source for non-invasive identification of the liver toxicity markers.

  16. Impact of TGF-β inhibition during acute exercise on Achilles tendon extracellular matrix

    DEFF Research Database (Denmark)

    Potter, Ross M; Huynh, Richard T; Volper, Brent D

    2017-01-01

    The purpose of this study was to evaluate the role of TGF-β1in regulating tendon extracellular matrix after acute exercise. Wistar rats exercised (n = 15) on a treadmill for four consecutive days (60 min/day) or maintained normal cage activity. After each exercise bout, the peritendinous space of...

  17. Specific extracellular matrix remodeling signature of colon hepatic metastases.

    Directory of Open Access Journals (Sweden)

    Maguy Del Rio

    Full Text Available To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment.

  18. Specialisation of extracellular matrix for function in tendons and ligaments

    Science.gov (United States)

    Birch, Helen L.; Thorpe, Chavaunne T.; Rumian, Adam P.

    2013-01-01

    Summary Tendons and ligaments are similar structures in terms of their composition, organisation and mechanical properties. The distinction between them stems from their anatomical location; tendons form a link between muscle and bone while ligaments link bones to bones. A range of overlapping functions can be assigned to tendon and ligaments and each structure has specific mechanical properties which appear to be suited for particular in vivo function. The extracellular matrix in tendon and ligament varies in accordance with function, providing appropriate mechanical properties. The most useful framework in which to consider extracellular matrix differences therefore is that of function rather than anatomical location. In this review we discuss what is known about the relationship between functional requirements, structural properties from molecular to gross level, cellular gene expression and matrix turnover. The relevance of this information is considered by reviewing clinical aspects of tendon and ligament repair and reconstructive procedures. PMID:23885341

  19. Increased levels of specific leukocyte- and platelet-derived substances during normal anti-tetanus antibody synthesis in patients with inactive Crohn disease

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Mortensen, T; Holten-Andersen, M

    2001-01-01

    /ml were inoculated with 1 ml (6 Lf units) of tetanus toxoid vaccine. The anti-tetanus antibody levels were determined in serum obtained before inoculation and after 7, 14 and 28 days, respectively. C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), histamine......, vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinases-1 (TIMP-1), plasminogen activator inhibitor type-1 (PAI-1) and myeloperoxidase (MPO) were determined in serum or plasma obtained on the same days. RESULTS: After inoculation anti-tetanus antibody levels were equally raised...

  20. Holistic face categorization in higher-level cortical visual areas of the normal and prosopagnosic brain: towards a non-hierarchical view of face perception

    Directory of Open Access Journals (Sweden)

    Bruno Rossion

    2011-01-01

    Full Text Available How a visual stimulus is initially categorized as a face in a network of human brain areas remains largely unclear. Hierarchical neuro-computational models of face perception assume that the visual stimulus is first decomposed in local parts in lower order visual areas. These parts would then be combined into a global representation in higher order face-sensitive areas of the occipito-temporal cortex. Here we tested this view in fMRI with visual stimuli that are categorized as faces based on their global configuration rather than their local parts (2-tones Mooney figures and Arcimboldo’s facelike paintings. Compared to the same inverted visual stimuli that are not categorized as faces, these stimuli activated the right middle fusiform gyrus (Fusiform face area, FFA and superior temporal sulcus (pSTS, with no significant activation in the posteriorly located inferior occipital gyrus (i.e., no occipital face area, OFA. This observation is strengthened by behavioral and neural evidence for normal face categorization of these stimuli in a brain-damaged prosopagnosic patient (PS whose intact right middle fusiform gyrus and superior temporal sulcus are devoid of any potential face-sensitive inputs from the lesioned right inferior occipital cortex. Together, these observations indicate that face-preferential activation may emerge in higher order visual areas of the right hemisphere without any face-preferential inputs from lower order visual areas, supporting a non-hierarchical view of face perception in the visual cortex.

  1. At the end of a two-year follow-up elevated TSH levels normalize or remain unchanged in most the children with subclinical hypothyroidism

    Directory of Open Access Journals (Sweden)

    De Luca Filippo

    2010-01-01

    Full Text Available Abstract Data about the natural evolution of subclinical hypothyroidism (SH in pediatric age are very scanty. Moreover all the available reports in both aged and young patients were based on unselected study populations including also patients with either thyroid disorders or other pathological causes that are well known to be able to affect SH development and evolution. Aim of the study by Wasniewska et al was to prospectively evaluate for the first time the natural course of SH in children and adolescents with no underlying diseases and no risk factors that might interfere with the progression of SH. On the basis of the 2-year follow-up results, the Authors concluded that: a the natural course of TSH values in a pediatric population with idiopathic SH is characterized by a progressive decrease over time; b the majority of patients (88% normalized or maintained unchanged their TSH; and c TSH changes were not associated with changes of either FT4 values or clinical status or auxological parameters. Study design of this study is very accurate and the results are robust, thus supporting the Authors' conclusions.

  2. Modulation of total IgE levels in serum of normal and athymic nude BALB/c mice by cells and exogenous antigenic stimulation

    NARCIS (Netherlands)

    Savelkoul, H.F.J.; Akker, van den T.W.; Soeting, P.W.C.; Oudenaren, van A.; Benner, R.

    1989-01-01

    Several different grades of T-system impairment were studied for their effects on the total serum IgE concentration in BALB/c mice. Homozygous athymic nu/nu mice and their heterozygous nu/ littermates were compared for serum IgE levels while kept under either barrier-maintained or conventional

  3. Mean Platelet Volume, Vitamin D and C Reactive Protein Levels in Normal Weight Children with Primary Snoring and Obstructive Sleep Apnea Syndrome.

    Directory of Open Access Journals (Sweden)

    Anna Maria Zicari

    Full Text Available Studies on Mean Platelet Volume (MPV in children with Sleep Disordered Breathing (SDB report conflicting results and the hypothesis of an intermittent hypoxemia leading to a systemic inflammation is reaching consensus. Vitamin D exerts anti-inflammatory properties and its deficiency has been supposed to play a role in sleep disorders. Emerging interest is rising about Primary Snoring (PS since it is reasonable that also undetectable alteration of hypoxia might predispose to an increased production of inflammatory mediators. In this perspective, in a group of children affected by SDB, our aim was to investigate MPV, vitamin D and C Reactive Protein (CRP levels, which had been previously evaluated separately in different studies focused only on Obstructive Sleep Apnea Syndrome (OSAS.We enrolled 137 children: 70 healthy controls (HC, 67 affected by SDB undergoing a polysomnographic evaluation, 22 with a diagnosis of PS and 45 with a diagnosis of OSAS. All patients underwent routine biochemical evaluations including blood cell counts, CRP and vitamin D.Children affected by SDB had a mean age of 8.49±2.19 and were prevalently males (23 females, 34%; 44 males, 66%. MPV levels were higher in OSAS and PS when compared to HC; platelet count (PLT and CRP levels were higher while Vitamin D levels were lower in children with SDB when compared to HC. MPV levels were correlated with PLT (r = -0.54; p<0.001, vitamin D (r = -0.39; p<0.001 and CRP (r = 0.21; p<0.01. A multiple regression was run to predict MPV levels from vitamin D, CRP and PLT and these variables significantly predicted MPV (F = 17.42, p<0.0001; adjusted R2 = 0.37. Only platelet count and vitamin D added statistically significantly to the prediction (p<0.05.The present study provides evidence of higher MPV and lower vitamin D levels in children with PS as well as in children with OSAS, and supports the underlying inflammation, hence, highlighting the importance of an early diagnosis of this

  4. Mean Platelet Volume, Vitamin D and C Reactive Protein Levels in Normal Weight Children with Primary Snoring and Obstructive Sleep Apnea Syndrome.

    Science.gov (United States)

    Zicari, Anna Maria; Occasi, Francesca; Di Mauro, Federica; Lollobrigida, Valeria; Di Fraia, Marco; Savastano, Vincenzo; Loffredo, Lorenzo; Nicita, Francesco; Spalice, Alberto; Duse, Marzia

    2016-01-01

    Studies on Mean Platelet Volume (MPV) in children with Sleep Disordered Breathing (SDB) report conflicting results and the hypothesis of an intermittent hypoxemia leading to a systemic inflammation is reaching consensus. Vitamin D exerts anti-inflammatory properties and its deficiency has been supposed to play a role in sleep disorders. Emerging interest is rising about Primary Snoring (PS) since it is reasonable that also undetectable alteration of hypoxia might predispose to an increased production of inflammatory mediators. In this perspective, in a group of children affected by SDB, our aim was to investigate MPV, vitamin D and C Reactive Protein (CRP) levels, which had been previously evaluated separately in different studies focused only on Obstructive Sleep Apnea Syndrome (OSAS). We enrolled 137 children: 70 healthy controls (HC), 67 affected by SDB undergoing a polysomnographic evaluation, 22 with a diagnosis of PS and 45 with a diagnosis of OSAS. All patients underwent routine biochemical evaluations including blood cell counts, CRP and vitamin D. Children affected by SDB had a mean age of 8.49±2.19 and were prevalently males (23 females, 34%; 44 males, 66%). MPV levels were higher in OSAS and PS when compared to HC; platelet count (PLT) and CRP levels were higher while Vitamin D levels were lower in children with SDB when compared to HC. MPV levels were correlated with PLT (r = -0.54; pchildren with PS as well as in children with OSAS, and supports the underlying inflammation, hence, highlighting the importance of an early diagnosis of this previously considered benign form of SDB.

  5. Response of extracellular zinc in the ventral hippocampus against novelty stress.

    Science.gov (United States)

    Takeda, Atsushi; Sakurada, Naomi; Kanno, Shingo; Minami, Akira; Oku, Naoto

    2006-10-01

    An extensive neuronal activity takes place in the hippocampus during exploratory behavior. However, the role of hippocampal zinc in exploratory behavior is poorly understood. To analyze the response of extracellular zinc in the hippocampus against novelty stress, rats were placed for 50 min in a novel environment once a day for 8 days. Extracellular glutamate in the hippocampus was increased during exploratory behavior on day 1, whereas extracellular zinc was decreased. The same phenomenon was observed during exploratory behavior on day 2 and extracellular zinc had returned to the basal level during exploratory behavior on day 8. To examine the significance of the decrease in extracellular zinc in exploratory activity, exploratory behavior was observed during perfusion with 1 mm CaEDTA, a membrane-impermeable zinc chelator. Locomotor activity in the novel environment was decreased by perfusion with CaEDTA. The decrease in extracellular zinc and the increase in extracellular glutamate in exploratory period were abolished by perfusion with CaEDTA. These results suggest that zinc uptake by hippocampal cells is linked to exploratory activity and is required for the activation of the glutamatergic neurotransmitter system. The zinc uptake may be involved in the response to painless psychological stress or in the cognitive processes.

  6. Baseline extracellular potassium level as an indicator of the rate of increase of the same on further storage in CPDA-1 whole blood units: a potential approach to complement FIFO system for prioritisation of blood bags for release from blood-banks.

    Science.gov (United States)

    Baliarsingh, S; Jaiswal, M

    2014-02-01

    Potassium levels in stored blood bags increases as they age. Hyperkalemia in transfused blood has undesirable cardiac effects. Within a 19-month period, baseline and weekly samples from 15 CPDA-1 whole blood bags were collected till 28 days of storage and analysed for potassium, sodium, uric acid, albumin and whole blood haemoglobin. One unit increase in baseline (0 day) potassium in extracellular fluid of blood units was associated with the following increases in potassium levels on later days of storage: around two unit increase at 1 week (r2 = 0·50, P values. For CPDA-1 blood bags (i) low baseline potassium blood bags might be preferred for transfusion in cases demanding a low potassium load and (ii) coordinating the ‘first-in-first-out’ (FIFO) policy with ‘early release of blood-bags with high initial potassium’ might be helpful in improving the release of suitable blood units from blood-banks.

  7. A comparative study of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels in the saliva of diabetic and normal patients.

    Science.gov (United States)

    Verma, M; Metgud, R; Madhusudan, A S; Verma, N; Saxena, M; Soni, A

    2014-10-01

    Diabetes has been reported to affect salivary glands adversely in humans and experimental models. Glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) are salivary enzymes that also are widely distributed in animal tissues. We determined GOT and GPT levels in saliva samples of 100 type 1 and 30 type 2 diabetic patients using reflectance spectrophotometry and compared them to 30 age and sex matched healthy controls. Statistically significant differences were observed in the mean values of GOT and GPT in type 1 diabetics compared to type 2 and control groups. Significantly higher GOT levels were found in the 1-20 year age group of type 1 diabetics. Our findings suggest that salivary gland damage is due to the same immunological attack that affects pancreatic β cells and results in type 1 diabetes.

  8. Vertebral artery variations and osseous anomaly at the C1-2 level diagnosed by 3D CT angiography in normal subjects

    Energy Technology Data Exchange (ETDEWEB)

    Wakao, Norimitsu; Kamiya, Mitsuhiro [Aichi Medical University, Department of Spine Center, Aichi (Japan); Aichi Medical University, Department of Orthopedic Surgery, Nagakute, Aichi (Japan); Takeuchi, Mikinobu; Hirasawa, Atsuhiko; Kawanami, Katsuhisa; Takayasu, Masakazu [Aichi Medical University, Department of Spine Center, Aichi (Japan); Nishimura, Manabu [Aichi Medical University, Department of Radiology, Nagakute, Aichi (Japan); Riew, K.D. [Washington University, Department of Orthopedic Surgery, St. Louis, MO (United States); Imagama, Shiro [Nagoya University, Department of Orthopedic Surgery, Nagoya, Aichi (Japan); Sato, Keiji [Aichi Medical University, Department of Orthopedic Surgery, Nagakute, Aichi (Japan)

    2014-10-15

    The craniovertebral junction is anatomically complicated. Representative vertebral artery (VA) variations include the persistent first intersegmental artery (FIA), fenestration of the VA above and below C1 (FEN), posterior inferior cerebellar artery (PICA) from C1/2, and high-riding VA (HRVA). The ponticulus posticus (PP) is a well-known osseous anomaly at C1. Although those anomalies are frequent in patients with cervical deformity, the prevalence of these in subjects with normal cervical spines is still unknown. The aim of this study is to investigate the variations and prevalence of vascular and osseous anomalies based on three-dimensional computed tomographic (3D CT) angiography in patients without any cervical diseases, such as rheumatoid arthritis, Klippel-Feil syndrome, or Down syndrome. Eligible subjects were patients who underwent 3D CT angiography by the Department of Otorhinolaryngology and Internal Medicine from January 2009 to October 2013 in our institution. The authors defined a HRVA as a C2 pedicle with a maximum diameter of 4 mm or less. Among 480 subjects with a mean age of 63.1 years, 387 patients were eligible. One hundred and eighteen subjects were female, and 269 were male. HRVA was observed in 10.1 % of patients (39 out of 387 cases), FIA in 1.8 % (7 cases), FEN in 1.3 % (5 cases), and PICA in 1.3 % (5 cases). PP was observed in 6.2 % of patients (24 cases). According to past reports, many VA anomalies could be attributed to congenital or acquired conditions (e.g., rheumatoid arthritis). However, VA anomalies appear to exist even in patients without any such cervical diseases. (orig.)

  9. The effect of intraoperative administration of dexamethasone for PONV prophylaxis on perioperative blood glucose level in obese and normal weight children.

    Science.gov (United States)

    Gnatzy, Richard; Hempel, Gunther; Kaisers, Udo X; Höhne, Claudia

    2015-11-01

    The incidence of postoperative nausea and vomiting (PONV) can be reduced by dexamethasone. Single-dose administration may cause elevated blood glucose levels in obese adults. No data are available for children. The aim was to evaluate perioperative blood glucose changes related to body weight in children who received dexamethasone. This prospective observational study included 62 children. All patients received total intravenous anesthesia and a single dose of dexamethasone (0.15 mg/kg, maximum 8 mg). Blood glucose levels were measured up to 6 h. Standard deviation scores (SDS) were calculated using age- and gender-specific body mass index (BMI) percentiles, pBlood glucose levels increased from 5.52±0.52 to 6.74±0.84 mmol/L 6 h after dexamethasone without correlation to the BMI-SDS. This study showed an increase of perioperative blood glucose (normoglycemic ranges) after single dose of dexamethasone, but no BMI-dependent effect was observed in children. Therefore, low-dose dexamethasone may be used in obese children for PONV prophylaxis.

  10. Dietary long chain n-3 polyunsaturated fatty acids prevent impaired social behaviour and normalize brain dopamine levels in food allergic mice.

    Science.gov (United States)

    de Theije, Caroline G M; van den Elsen, Lieke W J; Willemsen, Linette E M; Milosevic, Vanja; Korte-Bouws, Gerdien A H; Lopes da Silva, Sofia; Broersen, Laus M; Korte, S Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D

    2015-03-01

    Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the effect of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on food allergy-induced impaired social behaviour and associated deficits in prefrontal dopamine (DA) in mice. Mice were fed either control or n-3 LCPUFA-enriched diet before and during sensitization with whey. Social behaviour, acute allergic skin response and serum immunoglobulins were assessed. Monoamine levels were measured in brain and intestine and fatty acid content in brain. N-3 LCPUFA prevented impaired social behaviour of allergic mice. Moreover, n-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation into the brain and restored reduced levels of prefrontal DA and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid in allergic mice. In addition to these brain effects, n-3 LCPUFA supplementation reduced the allergic skin response and restored decreased intestinal levels of serotonin metabolite 5-hydroxyindoleacetic acid in allergic mice. N-3 LCPUFA may have beneficial effects on food allergy-induced deficits in social behaviour, either indirectly by reducing the allergic response and restoring intestinal 5-HT signalling, or directly by DHA incorporation into neuronal membranes, affecting the DA system. Therefore, it is of interest to further investigate the relevance of food allergy-enhanced impairments in social behaviour in humans and the potential benefits of dietary n-3 LCPUFA supplementation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Reliability and Validity of a Survey of Cat Caregivers on Their Cats’ Socialization Level in the Cat’s Normal Environment

    OpenAIRE

    Slater, Margaret; Garrison, Laurie; Miller, Katherine; Weiss, Emily; Makolinski, Kathleen; Drain, Natasha

    2013-01-01

    Simple Summary Many animal welfare organizations accept cats with no known behavioral history. It can be difficult to differentiate between a frightened but well-socialized cat and an unsocialized cat in an animal shelter environment. Making this distinction can save lives, yet currently there is no valid tool. Here we measured the quality of a survey designed to determine socialization level using information from the cat’s caregiver about a cat’s usual behavior around people in the cat’s no...

  12. Assessment of extracellular dehydration using saliva osmolality.

    Science.gov (United States)

    Ely, Brett R; Cheuvront, Samuel N; Kenefick, Robert W; Spitz, Marissa G; Heavens, Kristen R; Walsh, Neil P; Sawka, Michael N

    2014-01-01

    When substantial solute losses accompany body water an isotonic hypovolemia (extracellular dehydration) results. The potential for using blood or urine to assess extracellular dehydration is generally poor, but saliva is not a simple ultra-filtrate of plasma and the autonomic regulation of salivary gland function suggests the possibility that saliva osmolality (Sosm) may afford detection of extracellular dehydration via the influence of volume-mediated factors. This study aimed to evaluate the assessment of extracellular dehydration using Sosm. In addition, two common saliva collection methods and their effects on Sosm were compared. Blood, urine, and saliva samples were collected in 24 healthy volunteers during paired euhydration and dehydration trials. Furosemide administration and 12 h fluid restriction were used to produce extracellular dehydration. Expectoration and salivette collection methods were compared in a separate group of eight euhydrated volunteers. All comparisons were made using paired t-tests. The diagnostic potential of body fluids was additionally evaluated. Dehydration (3.1 ± 0.5% loss of body mass) decreased PV (-0.49 ± 0.12 L; -15.12 ± 3.94% change), but Sosm changes were marginal ( 0.05). Extracelluar dehydration was not detectable using plasma, urine, or saliva measures. Salivette and expectoration sampling methods produced similar, consistent results for Sosm, suggesting no methodological influence on Sosm.

  13. Extracellular histones in tissue injury and inflammation.

    Science.gov (United States)

    Allam, Ramanjaneyulu; Kumar, Santhosh V R; Darisipudi, Murthy N; Anders, Hans-Joachim

    2014-05-01

    Neutrophil NETosis is an important element of host defense as it catapults chromatin out of the cell to trap bacteria, which then are killed, e.g., by the chromatin's histone component. Also, during sterile inflammation TNF-alpha and other mediators trigger NETosis, which elicits cytotoxic effects on host cells. The same mechanism should apply to other forms of regulated necrosis including pyroptosis, necroptosis, ferroptosis, and cyclophilin D-mediated regulated necrosis. Beyond these toxic effects, extracellular histones also trigger thrombus formation and innate immunity by activating Toll-like receptors and the NLRP3 inflammasome. Thereby, extracellular histones contribute to the microvascular complications of sepsis, major trauma, small vessel vasculitis as well as acute liver, kidney, brain, and lung injury. Finally, histones prevent the degradation of extracellular DNA, which promotes autoimmunization, anti-nuclear antibody formation, and autoimmunity in susceptible individuals. Here, we review the current evidence on the pathogenic role of extracellular histones in disease and discuss how to target extracellular histones to improve disease outcomes.

  14. Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection.

    Science.gov (United States)

    da Silva, Vanessa Kappel; de Freitas, Betânia Souza; da Silva Dornelles, Arethuza; Nery, Laura Roesler; Falavigna, Lucio; Ferreira, Rafael Dal Ponte; Bogo, Maurício Reis; Hallak, Jaime Eduardo Cecílio; Zuardi, Antônio Waldo; Crippa, José Alexandre S; Schröder, Nadja

    2014-02-01

    We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats. Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits. It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation. Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats. We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group. Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.

  15. APOε2 and education in cognitively normal older subjects with high levels of AD pathology at autopsy: findings from the Nun Study.

    Science.gov (United States)

    Iacono, Diego; Zandi, Peter; Gross, Myron; Markesbery, William R; Pletnikova, Olga; Rudow, Gay; Troncoso, Juan C

    2015-06-10

    Asymptomatic Alzheimer's disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOε4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE could be associated with the different clinical outcomes between ASYMAD and MCI subjects despite equivalent AD pathology. A total of 523 brains from the Nun Study were screened for this investigation. The results showed higher APOε2 frequency (p < 0.001) in ASYMAD (19.2%) vs. MCI (0%) and vs. AD (4.7%). Furthermore, higher education in ASYMAD vs. MCI and AD (p < 0.05) was found. These novel autopsy-verified findings support the hypothesis of the beneficial effect of APOε2 and education, both which seem to act as contributing factors in delaying or forestalling the clinical manifestations of AD despite consistent levels of AD pathology.

  16. Consumption of tyrosine in royal jelly increases brain levels of dopamine and tyramine and promotes transition from normal to reproductive workers in queenless honey bee colonies.

    Science.gov (United States)

    Matsuyama, Syuhei; Nagao, Takashi; Sasaki, Ken

    2015-01-15

    Dopamine (DA) and tyramine (TA) have neurohormonal roles in the production of reproductive workers in queenless colonies of honey bees, but the regulation of these biogenic amines in the brain are still largely unclear. Nutrition is an important factor in promoting reproduction and might be involved in the regulation of these biogenic amines in the brain. To test this hypothesis, we examined the effect of oral treatments of tyrosine (Tyr; a common precursor of DA, TA and octopamine, and a component of royal jelly) in queenless workers and quantified the resulting production of biogenic amines. Tyrosine treatments enhanced the levels of DA, TA and their metabolites in the brain. Workers fed royal jelly had significantly larger brain levels of Tyr, DA, TA and the metabolites in the brains compared with those bees fed honey or sucrose (control). Treatment with Tyr also inhibited the behavior of workers outside of the hive and promoted ovarian development. These results suggest that there is a link between nutrition and the regulation of DA and TA in the brain to promote the production of reproductive workers in queenless honey bee colonies. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Strong association between non alcoholic fatty liver disease (NAFLD and low 25(OH vitamin D levels in an adult population with normal serum liver enzymes

    Directory of Open Access Journals (Sweden)

    Pozzilli Paolo

    2011-07-01

    Full Text Available Abstract Background Hypovitaminosis D has been recently recognized as a worldwide epidemic. Since vitamin D exerts significant metabolic activities, comprising free fatty acids (FFA flux regulation from the periphery to the liver, its deficiency may promote fat deposition into the hepatocytes. Aim of our study was to test the hypothesis of a direct association between hypovitaminosis D and the presence of NAFLD in subjects with various degree of insulin-resistance and related metabolic disorders. Methods We studied 262 consecutive subjects referred to the Diabetes and Metabolic Diseases clinics for metabolic evaluation. NAFLD (non-alcoholic fatty liver disease was diagnosed by upper abdomen ultrasonography, metabolic syndrome was identified according to the Third Report of National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATPIII modified criteria. Insulin-resistance was evaluated by means of HOMA-IR. Fatty-Liver-Index, a recently identified correlate of NAFLD, was also estimated. Serum 25(OHvitamin D was measured by colorimetric method. Results Patients with NAFLD (n = 162,61.8% had reduced serum 25(OH vitamin D levels compared to subjects without NAFLD (14.8 ± 9.2 vs 20.5 ± 9.7 ng/ml, p Conclusions Low 25(OHvitamin D levels are associated with the presence of NAFLD independently from metabolic syndrome, diabetes and insulin-resistance profile.

  18. Depressed immune surveillance against cancer: role of deficient T cell: extracellular matrix interactions.

    Science.gov (United States)

    Górski, A; Castronovo, V; Stepień-Sopniewska, B; Grieb, P; Ryba, M; Mrowiec, T; Korczak-Kowalska, G; Wierzbicki, P; Matysiak, W; Dybowska, B

    1994-07-01

    Although T cells infiltrate malignant tumors, the local immune response is usually inefficient and tumors escape destruction. While extracellular matrix proteins strongly costimulate T cell responses in normal individuals, our studies indicate that peripheral blood T cells from cancer patients and tumor infiltrating cells respond poorly or are resistant to stimulative signals mediated by collagen I and IV and fibronectin. Moreover, the adhesive properties of cancer T cells are markedly depressed. Those functional deficiencies are paralleled by variable deficits in integrin and non-integrin T cell receptors for extracellular matrix. Immunotherapy with BCG causes a dramatic but transient increase in T cell: ECM interactions.

  19. Extracellular Alkalinization as a Defense Response in Potato Cells.

    Science.gov (United States)

    Moroz, Natalia; Fritch, Karen R; Marcec, Matthew J; Tripathi, Diwaker; Smertenko, Andrei; Tanaka, Kiwamu

    2017-01-01

    A quantitative and robust bioassay to assess plant defense response is important for studies of disease resistance and also for the early identification of disease during pre- or non-symptomatic phases. An increase in extracellular pH is known to be an early defense response in plants. In this study, we demonstrate extracellular alkalinization as a defense response in potatoes. Using potato suspension cell cultures, we observed an alkalinization response against various pathogen- and plant-derived elicitors in a dose- and time-dependent manner. We also assessed the defense response against a variety of potato pathogens, such as protists ( Phytophthora infestans and Spongospora subterranea ) and fungi ( Verticillium dahliae and Colletotrichum coccodes ). Our results show that extracellular pH increases within 30 min in proportion to the number of pathogen spores added. Consistently with the alkalinization effect, the higher transcription level of several defense-related genes and production of reactive oxygen species was observed. Our results demonstrate that the alkalinization response is an effective marker to study early stages of defense response in potatoes.

  20. Comparison of low-abundance biomarker levels in capillary-collected nonstimulated tears and washout tears of aqueous-deficient and normal patients.

    Science.gov (United States)

    Guyette, Nicole; Williams, Larezia; Tran, My-Tho; Than, Tammy; Bradley, John; Kehinde, Lucy; Edwards, Clara; Beasley, Mark; Fullard, Roderick

    2013-05-01

    Low tear volume limits the use of nonstimulated (NS) microcapillary tear collection in aqueous-deficient (AD) patients. Adding a small amount of "washout" fluid to the eye prior to tear collection is a potentially viable alternative method for abundant proteins, but is relatively untested for low-abundance biomarkers. This study determined the feasibility of the washout (WO) method as an NS alternative for low-abundance biomarkers. NS and WO biomarker profiles were compared between AD patients and non-AD controls to determine if the two methods identify the same intergroup differences. Matching NS and WO tears were collected from 48 patients by micropipette, the WO sample after instillation of 10 μL saline. Tear cytokine levels were measured by 27-Plex Bio-Rad assay. Bland-Altman analyses for each biomarker determined the agreement between tear sample types. Patients were grouped as AD or non-AD based on Schirmer score to determine if NS profile between-group differences were preserved in WO tears. Bland-Altman plots showed good biomarker level agreement between NS and WO tears for most cytokines. Five biomarkers, among those most often cited as differing in AD dry eye, differed significantly between non-AD and AD groups in both tear types. Additional biomarker differences were seen in NS tears only. The WO tear collection method is a viable alternative to NS tears for many low-abundance biomarkers and is able to replicate major NS tear differences between dry eye groups. More subtle intergroup differences are lost in WO samples because of reduced statistical power.

  1. Shaping Synapses by the Neural Extracellular Matrix

    Directory of Open Access Journals (Sweden)

    Maura Ferrer-Ferrer

    2018-05-01

    Full Text Available Accumulating data support the importance of interactions between pre- and postsynaptic neuronal elements with astroglial processes and extracellular matrix (ECM for formation and plasticity of chemical synapses, and thus validate the concept of a tetrapartite synapse. Here we outline the major mechanisms driving: (i synaptogenesis by secreted extracellular scaffolding molecules, like thrombospondins (TSPs, neuronal pentraxins (NPs and cerebellins, which respectively promote presynaptic, postsynaptic differentiation or both; (ii maturation of synapses via reelin and integrin ligands-mediated signaling; and (iii regulation of synaptic plasticity by ECM-dependent control of induction and consolidation of new synaptic configurations. Particularly, we focused on potential importance of activity-dependent concerted activation of multiple extracellular proteases, such as ADAMTS4/5/15, MMP9 and neurotrypsin, for permissive and instructive events in synaptic remodeling through localized degradation of perisynaptic ECM and generation of proteolytic fragments as inducers of synaptic plasticity.

  2. Calsequestrin content and SERCA determine normal and maximal Ca2+ storage levels in sarcoplasmic reticulum of fast- and slow-twitch fibres of rat.

    Science.gov (United States)

    Murphy, Robyn M; Larkins, Noni T; Mollica, Janelle P; Beard, Nicole A; Lamb, Graham D

    2009-01-15

    Whilst calsequestrin (CSQ) is widely recognized as the primary Ca2+ buffer in the sarcoplasmic reticulum (SR) in skeletal muscle fibres, its total buffering capacity and importance have come into question. This study quantified the absolute amount of CSQ isoform 1 (CSQ1, the primary isoform) present in rat extensor digitorum longus (EDL) and soleus fibres, and related this to their endogenous and maximal SR Ca2+ content. Using Western blotting, the entire constituents of minute samples of muscle homogenates or segments of individual muscle fibres were compared with known amounts of purified CSQ1. The fidelity of the analysis was proven by examining the relative signal intensity when mixing muscle samples and purified CSQ1. The CSQ1 contents of EDL fibres, almost exclusively type II fibres, and soleus type I fibres [SOL (I)] were, respectively, 36 +/- 2 and 10 +/- 1 micromol (l fibre volume)(-1), quantitatively accounting for the maximal SR Ca2+ content of each. Soleus type II [SOL (II)] fibres (approximately 20% of soleus fibres) had an intermediate amount of CSQ1. Every SOL (I) fibre examined also contained some CSQ isoform 2 (CSQ2), which was absent in every EDL and other type II fibre except for trace amounts in one case. Every EDL and other type II fibre had a high density of SERCA1, the fast-twitch muscle sarco(endo)plasmic reticulum Ca2+-ATPase isoform, whereas there was virtually no SERCA1 in any SOL (I) fibre. Maximal SR Ca2+ content measured in skinned fibres increased with CSQ1 content, and the ratio of endogenous to maximal Ca2+ content was inversely correlated with CSQ1 content. The relative SR Ca2+ content that could be maintained in resting cytoplasmic conditions was found to be much lower in EDL fibres than in SOL (I) fibres (approximately 20 versus >60%). Leakage of Ca2+ from the SR in EDL fibres could be substantially reduced with a SR Ca2+ pump blocker and increased by adding creatine to buffer cytoplasmic [ADP] at a higher level, both results

  3. Extracellular enzyme kinetics scale with resource availability

    Science.gov (United States)

    Sinsabaugh, Robert L.; Belnap, Jayne; Findlay, Stuart G.; Follstad Shah, Jennifer J.; Hill, Brian H.; Kuehn, Kevin A.; Kuske, Cheryl; Litvak, Marcy E.; Martinez, Noelle G.; Moorhead, Daryl L.; Warnock, Daniel D.

    2014-01-01

    Microbial community metabolism relies on external digestion, mediated by extracellular enzymes that break down complex organic matter into molecules small enough for cells to assimilate. We analyzed the kinetics of 40 extracellular enzymes that mediate the degradation and assimilation of carbon, nitrogen and phosphorus by diverse aquatic and terrestrial microbial communities (1160 cases). Regression analyses were conducted by habitat (aquatic and terrestrial), enzyme class (hydrolases and oxidoreductases) and assay methodology (low affinity and high affinity substrates) to relate potential reaction rates to substrate availability. Across enzyme classes and habitats, the scaling relationships between apparent Vmax and apparent Km followed similar power laws with exponents of 0.44 to 0.67. These exponents, called elasticities, were not statistically distinct from a central value of 0.50, which occurs when the Km of an enzyme equals substrate concentration, a condition optimal for maintenance of steady state. We also conducted an ecosystem scale analysis of ten extracellular hydrolase activities in relation to soil and sediment organic carbon (2,000–5,000 cases/enzyme) that yielded elasticities near 1.0 (0.9 ± 0.2, n = 36). At the metabolomic scale, the elasticity of extracellular enzymatic reactions is the proportionality constant that connects the C:N:P stoichiometries of organic matter and ecoenzymatic activities. At the ecosystem scale, the elasticity of extracellular enzymatic reactions shows that organic matter ultimately limits effective enzyme binding sites. Our findings suggest that one mechanism by which microbial communities maintain homeostasis is regulating extracellular enzyme expression to optimize the short-term responsiveness of substrate acquisition. The analyses also show that, like elemental stoichiometry, the fundamental attributes of enzymatic reactions can be extrapolated from biochemical to community and ecosystem scales.

  4. The association between Western and Prudent dietary patterns and fasting blood glucose levels in type 2 diabetes and normal glucose metabolism in older Australian adults.

    Science.gov (United States)

    Walsh, Erin I; Jacka, Felice N; Butterworth, Peter; Anstey, Kaarin J; Cherbuin, Nicolas

    2017-06-01

    High blood glucose and type 2 diabetes are associated with a range of adverse health and cognitive outcomes. One factor that contributes to high blood glucose and type 2 diabetes is dietary intake. This study investigated the relationship between dietary patterns, fasting blood glucose and diabetes status in a sample of 209 participants aged 60-65. Blood plasma glucose was measured from venous blood samples. Individual Prudent and Western dietary patterns were estimated from a self-completed food frequency questionnaire. The relationship between dietary patterns, diabetes, and blood glucose was assessed via general linear model analyses controlling for age, sex, height, and total caloric intake. Results indicated that there was no association between Prudent diet and fasting blood glucose levels, or type 2 diabetes. In contrast, an individual in the upper tertile for Western dietary score had a significantly higher risk of having diabetes than an individual in the lower tertile for Western dietary score. However, there was no significant association between Western diet and fasting blood glucose. Western diet may be associated with type 2 diabetes through mechanisms beyond impacting blood plasma glucose directly. The fact that the association between Western diet and type 2 diabetes remained even when total caloric intake was controlled for highlights the need for policy and population health interventions targeting the reduction of unhealthy food consumption.

  5. The extracellular domain of neurotrophin receptor p75 as a candidate biomarker for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Shepheard, Stephanie R; Chataway, Tim; Schultz, David W; Rush, Robert A; Rogers, Mary-Louise

    2014-01-01

    Objective biomarkers for amyotrophic lateral sclerosis would facilitate the discovery of new treatments. The common neurotrophin receptor p75 is up regulated and the extracellular domain cleaved from injured neurons and peripheral glia in amyotrophic lateral sclerosis. We have tested the hypothesis that urinary levels of extracellular neurotrophin receptor p75 serve as a biomarker for both human motor amyotrophic lateral sclerosis and the SOD1(G93A) mouse model of the disease. The extracellular domain of neurotrophin receptor p75 was identified in the urine of amyotrophic lateral sclerosis patients by an immuno-precipitation/western blot procedure and confirmed by mass spectrometry. An ELISA was established to measure urinary extracellular neurotrophin receptor p75. The mean value for urinary extracellular neurotrophin receptor p75 from 28 amyotrophic lateral sclerosis patients measured by ELISA was 7.9±0.5 ng/mg creatinine and this was significantly higher (pneurotrophin receptor p75 was also readily detected in SOD1(G93A) mice by immuno-precipitation/western blot before the onset of clinical symptoms. These findings indicate a significant relation between urinary extracellular neurotrophin receptor p75 levels and disease progression and suggests that it may be a useful marker of disease activity and progression in amyotrophic lateral sclerosis.

  6. Delivery of viral vectors to tumor cells: extracellular transport, systemic distribution, and strategies for improvement.

    Science.gov (United States)

    Wang, Yong; Yuan, Fan

    2006-01-01

    It is a challenge to deliver therapeutic genes to tumor cells using viral vectors because (i) the size of these vectors are close to or larger than the space between fibers in extracellular matrix and (ii) viral proteins are potentially toxic in normal tissues. In general, gene delivery is hindered by various physiological barriers to virus transport from the site of injection to the nucleus of tumor cells and is limited by normal tissue tolerance of toxicity determined by local concentrations of transgene products and viral proteins. To illustrate the obstacles encountered in the delivery and yet limit the scope of discussion, this review focuses only on extracellular transport in solid tumors and distribution of viral vectors in normal organs after they are injected intravenously or intratumorally. This review also discusses current strategies for improving intratumoral transport and specificity of viral vectors.

  7. Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy.

    Science.gov (United States)

    Mendias, Christopher L; Schwartz, Andrew J; Grekin, Jeremy A; Gumucio, Jonathan P; Sugg, Kristoffer B

    2017-03-01

    Skeletal muscle can adapt to increased mechanical loads by undergoing hypertrophy. Transient reductions in whole muscle force production have been reported during the onset of hypertrophy, but contractile changes in individual muscle fibers have not been previously studied. Additionally, the extracellular matrix (ECM) stores and transmits forces from muscle fibers to tendons and bones, and determining how the ECM changes during hypertrophy is important in understanding the adaptation of muscle tissue to mechanical loading. Using the synergist ablation model, we sought to measure changes in muscle fiber contractility, collagen content, and cross-linking, and in the expression of several genes and activation of signaling proteins that regulate critical components of myogenesis and ECM synthesis and remodeling during muscle hypertrophy. Tissues were harvested 3, 7, and 28 days after induction of hypertrophy, and nonoverloaded rats served as controls. Muscle fiber specific force (sF o ), which is the maximum isometric force normalized to cross-sectional area, was reduced 3 and 7 days after the onset of mechanical overload, but returned to control levels by 28 days. Collagen abundance displayed a similar pattern of change. Nearly a quarter of the transcriptome changed over the course of overload, as well as the activation of signaling pathways related to hypertrophy and atrophy. Overall, this study provides insight into fundamental mechanisms of muscle and ECM growth, and indicates that although muscle fibers appear to have completed remodeling and regeneration 1 mo after synergist ablation, the ECM continues to be actively remodeling at this time point. NEW & NOTEWORTHY This study utilized a rat synergist ablation model to integrate changes in single muscle fiber contractility, extracellular matrix composition, activation of important signaling pathways in muscle adaption, and corresponding changes in the muscle transcriptome to provide novel insight into the basic

  8. Regulation of extracellular matrix organization by BMP signaling in Caenorhabditis elegans.

    Science.gov (United States)

    Schultz, Robbie D; Bennett, Emily E; Ellis, E Ann; Gumienny, Tina L

    2014-01-01

    In mammals, Bone Morphogenetic Protein (BMP) pathway signaling is important for the growth and homeostasis of extracellular matrix, including basement membrane remodeling, scarring, and bone growth. A conserved BMP member in Caenorhabditis elegans, DBL-1, regulates body length in a dose-sensitive manner. Loss of DBL-1 pathway signaling also results in increased anesthetic sensitivity. However, the physiological basis of these pleiotropic phenotypes is largely unknown. We created a DBL-1 over-expressing strain and show that sensitivity to anesthetics is inversely related to the dose of DBL-1. Using pharmacological, genetic analyses, and a novel dye permeability assay for live, microwave-treated animals, we confirm that DBL-1 is required for the barrier function of the cuticle, a specialized extracellular matrix. We show that DBL-1 signaling is required to prevent animals from forming tail-entangled aggregates in liquid. Stripping lipids off the surface of wild-type animals recapitulates this phenotype. Finally, we find that DBL-1 signaling affects ultrastructure of the nematode cuticle in a dose-dependent manner, as surface lipid content and cuticular organization are disrupted in animals with genetically altered DBL-1 levels. We propose that the lipid layer coating the nematode cuticle normally prevents tail entanglement, and that reduction of this layer by loss of DBL-1 signaling promotes aggregation. This work provides a physiological mechanism that unites the DBL-1 signaling pathway roles of not only body size regulation and drug responsiveness, but also the novel Hoechst 33342 staining and aggregation phenotypes, through barrier function, content, and organization of the cuticle.

  9. Regulation of extracellular matrix organization by BMP signaling in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Robbie D Schultz

    Full Text Available In mammals, Bone Morphogenetic Protein (BMP pathway signaling is important for the growth and homeostasis of extracellular matrix, including basement membrane remodeling, scarring, and bone growth. A conserved BMP member in Caenorhabditis elegans, DBL-1, regulates body length in a dose-sensitive manner. Loss of DBL-1 pathway signaling also results in increased anesthetic sensitivity. However, the physiological basis of these pleiotropic phenotypes is largely unknown. We created a DBL-1 over-expressing strain and show that sensitivity to anesthetics is inversely related to the dose of DBL-1. Using pharmacological, genetic analyses, and a novel dye permeability assay for live, microwave-treated animals, we confirm that DBL-1 is required for the barrier function of the cuticle, a specialized extracellular matrix. We show that DBL-1 signaling is required to prevent animals from forming tail-entangled aggregates in liquid. Stripping lipids off the surface of wild-type animals recapitulates this phenotype. Finally, we find that DBL-1 signaling affects ultrastructure of the nematode cuticle in a dose-dependent manner, as surface lipid content and cuticular organization are disrupted in animals with genetically altered DBL-1 levels. We propose that the lipid layer coating the nematode cuticle normally prevents tail entanglement, and that reduction of this layer by loss of DBL-1 signaling promotes aggregation. This work provides a physiological mechanism that unites the DBL-1 signaling pathway roles of not only body size regulation and drug responsiveness, but also the novel Hoechst 33342 staining and aggregation phenotypes, through barrier function, content, and organization of the cuticle.

  10. Engineering extracellular matrix through nanotechnology.

    Science.gov (United States)

    Kelleher, Cassandra M; Vacanti, Joseph P

    2010-12-06

    The goal of tissue engineering is the creation of a living device that can restore, maintain or improve tissue function. Behind this goal is a new idea that has emerged from twentieth century medicine, science and engineering. It is preceded by centuries of human repair and replacement with non-living materials adapted to restore function and cosmetic appearance to patients whose tissues have been destroyed by disease, trauma or congenital abnormality. The nineteenth century advanced replacement and repair strategies based on moving living structures from a site of normal tissue into a site of defects created by the same processes. Donor skin into burn wounds, tendon transfers, intestinal replacements into the urinary tract, toes to replace fingers are all examples. The most radical application is that of vital organ transplantation in which a vital part such as heart, lung or liver is removed from one donor, preserved for transfer and implanted into a patient dying of end-stage organ failure. Tissue engineering and regenerative medicine have advanced a general strategy combining the cellular elements of living tissue with sophisticated biomaterials to produce living structures of sufficient size and function to improve patients' lives. Multiple strategies have evolved and the application of nanotechnology can only improve the field. In our era, by necessity, any medical advance must be successfully commercialized to allow widespread application to help the greatest number of patients. It follows that business models and regulatory agencies must adapt and change to enable these new technologies to emerge. This brief review will discuss the science of nanotechnology and how it has been applied to this evolving field. We will then briefly summarize the history of commercialization of tissue engineering and suggest that nanotechnology may be of use in breeching the barriers to commercialization although its primary mission is to improve the technology by solving some

  11. Normal Pressure Hydrocephalus (NPH)

    Science.gov (United States)

    ... local chapter Join our online community Normal Pressure Hydrocephalus (NPH) Normal pressure hydrocephalus is a brain disorder ... Symptoms Diagnosis Causes & risks Treatments About Normal Pressure Hydrocephalus Normal pressure hydrocephalus occurs when excess cerebrospinal fluid ...

  12. Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

    Science.gov (United States)

    Hansen, R K; Bissell, M J

    2010-01-01

    The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function. PMID:10903527

  13. Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, R K; Bissell, M J

    2000-06-01

    The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function.

  14. Royal Society Scientific Meeting: Extracellular vesicles in the tumour microenvironment.

    Science.gov (United States)

    Pink, Ryan Charles; Elmusrati, Areeg A; Lambert, Daniel; Carter, David Raul Francisco

    2018-01-05

    Cancer cells do not grow as an isolated homogeneous mass; tumours are, in fact, complex and heterogeneous collections of cancer and surrounding stromal cells, collectively termed the tumour microenvironment. The interaction between cancer cells and stromal cells in the tumour microenvironment has emerged as a key concept in the regulation of cancer progression. Understanding the intercellular dialogue in the tumour microenvironment is therefore an important goal. One aspect of this dialogue that has not been appreciated until recently is the role of extracellular vesicles (EVs). EVs are small vesicles released by cells under both normal and pathological conditions; they can transfer biological molecules between cells leading to changes in phenotype. EVs have emerged as important regulators of biological processes and can be dysregulated in diseases such as cancer; rapidly growing interest in their biology and therapeutic potential led to the Royal Society hosting a Scientific Meeting to explore the roles of EVs in the tumour microenvironment. This cross-disciplinary meeting explored examples of how aberrant crosstalk between tumour and stromal cells can promote cancer progression, and how such signalling can be targeted for diagnostic, prognostic and therapeutic benefit. In this review, and the special edition of Philosophical Transactions of the Royal Society B that follows, we will provide an overview of the content and outcomes of this exciting meeting.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'. © 2017 The Author(s).

  15. An extracellular subtilase switch for immune priming in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Vicente Ramírez

    Full Text Available In higher eukaryotes, induced resistance associates with acquisition of a priming state of the cells for a more effective activation of innate immunity; however, the nature of the components for mounting this type of immunological memory is not well known. We identified an extracellular subtilase from Arabidopsis, SBT3.3, the overexpression of which enhances innate immune responses while the loss of function compromises them. SBT3.3 expression initiates a durable autoinduction mechanism that promotes chromatin remodeling and activates a salicylic acid(SA-dependent mechanism of priming of defense genes for amplified response. Moreover, SBT3.3 expression-sensitized plants for enhanced expression of the OXI1 kinase gene and activation of MAP kinases following pathogen attack, providing additional clues for the regulation of immune priming by SBT3.3. Conversely, in sbt3.3 mutant plants pathogen-mediated induction of SA-related defense gene expression is drastically reduced and activation of MAP kinases inhibited. Moreover, chromatin remodeling of defense-related genes normally associated with activation of an immune priming response appear inhibited in sbt3.3 plants, further indicating the importance of the extracellular SBT3.3 subtilase in the establishment of immune priming. Our results also point to an epigenetic control in the regulation of plant immunity, since SBT3.3 is up-regulated and priming activated when epigenetic control is impeded. SBT3.3 represents a new regulator of primed immunity.

  16. Normal Levels of Plasma Free Carnitine and Acylcarnitines in Follow-Up Samples From a Presymptomatic Case of Carnitine Palmitoyl Transferase 1 (CPT1) Deficiency Detected Through Newborn Screening in Denmark

    DEFF Research Database (Denmark)

    Borch, Luise; Lund, Allan; Wibrand, Flemming

    2011-01-01

    of presymptomatic CPT1A deficiency detected through newborn screening in Denmark with diagnostic levels of carnitine and acylcarnitines in the initial dried blood spot. Levels of plasma-free carnitine and acylcarnitines in follow-up samples were normal, but reverted to diagnostic levels when the patient developed...... clinical symptoms at the age of 8 months. At that time, a diagnosis of CPT1A deficiency was confirmed by sequence analysis of the CPT1A gene revealing homozygosity for a novel c.167C>T variation in exon 3. Enzyme activity measurements showed a relatively mild enzyme defect with a decreased residual enzyme...... activity of 17–25%. We conclude that CPT1A gene testing and/or enzyme assay is mandatory to confirm an abnormal newborn screen suggesting CPT1A deficiency to avoid delayed diagnoses....

  17. Extracellular metabolites in the cortex and hippocampus of epileptic patients.

    Science.gov (United States)

    Cavus, Idil; Kasoff, Willard S; Cassaday, Michael P; Jacob, Ralph; Gueorguieva, Ralitza; Sherwin, Robert S; Krystal, John H; Spencer, Dennis D; Abi-Saab, Walid M

    2005-02-01

    Interictal brain energy metabolism and glutamate-glutamine cycling are impaired in epilepsy and may contribute to seizure generation. We used the zero-flow microdialysis method to measure the extracellular levels of glutamate, glutamine, and the major energy substrates glucose and lactate in the epileptogenic and the nonepileptogenic cortex and hippocampus of 38 awake epileptic patients during the interictal period. Depth electrodes attached to microdialysis probes were used to identify the epileptogenic and the nonepileptogenic sites. The epileptogenic hippocampus had surprisingly high basal glutamate levels, low glutamine/glutamate ratio, high lactate levels, and indication for poor glucose utilization. The epileptogenic cortex had only marginally increased glutamate levels. We propose that interictal energetic deficiency in the epileptogenic hippocampus could contribute to impaired glutamate reuptake and glutamate-glutamine cycling, resulting in persistently increased extracellular glutamate, glial and neuronal toxicity, increased lactate production together with poor lactate and glucose utilization, and ultimately worsening energy metabolism. Our data suggest that a different neurometabolic process underlies the neocortical epilepsies.

  18. Zero net flux estimates of septal extracellular glucose levels and the effects of glucose on septal extracellular GABA levels

    OpenAIRE

    Krebs-Kraft, Desiree L.; Rauw, Gail; Baker, Glen B.; Parent, Marise B.

    2009-01-01

    Although hippocampal infusions of glucose enhance memory, we have found repeatedly that septal glucose infusions impair memory when γ-aminobutyric acid (GABA) receptors are activated. For instance, hippocampal glucose infusions reverse the memory-impairing effects of co-infusions of the GABA agonist muscimol, whereas septal glucose infusions exacerbate memory deficits produced by muscimol. One potential explanation for these deleterious effects of glucose in the septum is that there are highe...

  19. Optimization of extracellular catalase production from Aspergillus ...

    African Journals Online (AJOL)

    The studies of the effect of each variable and the establishment of a correlation between the response of enzyme activity and variables revealed that the link is a multiple linear regression form. The optimization was carried out through a simplex algorithm. The amount of extracellular catalase produced by the strain in the ...

  20. Managing Brain Extracellular K(+) during Neuronal Activity

    DEFF Research Database (Denmark)

    Larsen, Brian Roland; Stoica, Anca; MacAulay, Nanna

    2016-01-01

    characteristics required to fulfill their distinct physiological roles in clearance of K(+) from the extracellular space in the face of neuronal activity. Understanding the nature, impact and effects of the various Na(+)/K(+)-ATPase isoform combinations in K(+) management in the central nervous system might...... understanding of the pathological events occurring during disease....

  1. Extracellular vesicles: fundamentals and clinical relevance

    Directory of Open Access Journals (Sweden)

    Wael Nassar

    2015-01-01

    Full Text Available All types of cells of eukaryotic organisms produce and release small nanovesicles into their extracellular environment. Early studies have described these vesicles as ′garbage bags′ only to remove obsolete cellular molecules. Valadi and colleagues, in 2007, were the first to discover the capability of circulating extracellular vesicles (EVs to horizontally transfer functioning gene information between cells. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemoresistance, genetic exchange, and signaling pathway activation through growth factor/receptor transfer. EVs represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins, and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived EVs not only represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we′ll be addressing the characteristics of different types of extracellular EVs, as well as their clinical relevance and potential as diagnostic markers, and also define therapeutic options.

  2. Extracellular space diffusion and extrasynaptic transmission

    Czech Academy of Sciences Publication Activity Database

    Vargová, Lýdia; Syková, Eva

    2008-01-01

    Roč. 57, Suppl.3 (2008), S89-S99 ISSN 0862-8408 R&D Projects: GA MŠk 1M0538; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50390512 Keywords : Diffusion * Extracellular volume * Tortuosity Subject RIV: FH - Neurology Impact factor: 1.653, year: 2008

  3. Integrins and extracellular matrix in mechanotransduction

    Directory of Open Access Journals (Sweden)

    Ramage L

    2011-12-01

    Full Text Available Lindsay RamageQueen’s Medical Research Institute, University of Edinburgh, Edinburgh, UKAbstract: Integrins are a family of cell surface receptors which mediate cell–matrix and cell–cell adhesions. Among other functions they provide an important mechanical link between the cells external and intracellular environments while the adhesions that they form also have critical roles in cellular signal-transduction. Cell–matrix contacts occur at zones in the cell surface where adhesion receptors cluster and when activated the receptors bind to ligands in the extracellular matrix. The extracellular matrix surrounds the cells of tissues and forms the structural support of tissue which is particularly important in connective tissues. Cells attach to the extracellular matrix through specific cell-surface receptors and molecules including integrins and transmembrane proteoglycans. Integrins work alongside other proteins such as cadherins, immunoglobulin superfamily cell adhesion molecules, selectins, and syndecans to mediate cell–cell and cell–matrix interactions and communication. Activation of adhesion receptors triggers the formation of matrix contacts in which bound matrix components, adhesion receptors, and associated intracellular cytoskeletal and signaling molecules form large functional, localized multiprotein complexes. Cell–matrix contacts are important in a variety of different cell and tissue properties including embryonic development, inflammatory responses, wound healing, and adult tissue homeostasis. This review summarizes the roles and functions of integrins and extracellular matrix proteins in mechanotransduction.Keywords: ligand binding, α subunit, ß subunit, focal adhesion, cell differentiation, mechanical loading, cell–matrix interaction

  4. Interaction of acetamiprid with extracellular polymeric substances ...

    African Journals Online (AJOL)

    Extracellular polymeric substances (EPS) are important components of activated sludge and it plays an important role in removing pollutants. The interaction between EPS and organic pollutants is still little known. In the present study, the interaction of soluble/bound EPS with acetamiprid, a neonicotinoid insecticide, was ...

  5. Optimization of extracellular catalase production from Aspergillus ...

    African Journals Online (AJOL)

    aghomotsegin

    extracellular catalase produced by the strain in the optimized medium was about four times higher than ... celial and unicellular fungi in synthetic media (Kurakov et .... covering the appropriate range and the broad calibration kit ... This optimization allowed us to define new cultural con- ..... Ann. New York Academy Sci.

  6. Production of extracellular aspartic protease in submerged ...

    African Journals Online (AJOL)

    Fungal milk-clotting enzymes have gained value as bovine Chymosin substitutes in the cheese industry. In this work, the effects of culture conditions on the production of extracellular milk clotting enzymes from Mucor mucedo DSM 809 in submerged fermentation were studied. The maximum activity was observed after 48 h ...

  7. Extracellular matrix and tissue engineering applications

    NARCIS (Netherlands)

    Fernandes, H.A.M.; Moroni, Lorenzo; van Blitterswijk, Clemens; de Boer, Jan

    2009-01-01

    The extracellular matrix is a key component during regeneration and maintenance of tissues and organs, and it therefore plays a critical role in successful tissue engineering as well. Tissue engineers should recognise that engineering technology can be deduced from natural repair processes. Due to

  8. Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Federica Ciregia

    2017-08-01

    Full Text Available Extracellular vesicles (EVs can be classified into apoptotic bodies, microvesicles (MVs, and exosomes, based on their origin or size. Exosomes are the smallest and best characterized vesicles which derived from the endosomal system. These vesicles are released from many different cell types including neuronal cells and their functions in the nervous system are investigated. They have been proposed as novel means for intercellular communication, which takes part not only to the normal neuronal physiology but also to the transmission of pathogenic proteins. Indeed, exosomes are fundamental to assemble and transport proteins during development, but they can also transfer neurotoxic misfolded proteins in pathogenesis. The present review will focus on their roles in neurological diseases, specifically brain tumors, such as glioblastoma (GBM, neuroblastoma (NB, medulloblastoma (MB, and metastatic brain tumors and chronic neurodegenerative diseases, such as Alzheimer, Parkinson, multiple sclerosis (MS, amyotrophic lateral sclerosis (ALS, Huntington, and Prion diseseases highlighting their involvement in spreading neurotoxicity, in therapeutics, and in pathogenesis.

  9. LFPy: A tool for biophysical simulation of extracellular potentials generated by detailed model neurons

    Directory of Open Access Journals (Sweden)

    Henrik eLindén

    2014-01-01

    Full Text Available Electrical extracellular recordings, i.e., recordings of the electrical potentials in the extracellular medium between cells, have been a main work-horse in electrophysiology for almost a century. The high-frequency part of the signal (>=500 Hz, i.e., themulti-unit activity (MUA, contains information about the firing of action potentials in surrounding neurons, while the low-frequency part, the local field potential (LFP, contains information about how these neurons integrate synaptic inputs. As the recorded extracellular signals arise from multiple neural processes, their interpretation is typically ambiguous and difficult. Fortunately, a precise biophysical modeling scheme linking activity at the cellular level and the recorded signal has been established: the extracellular potential can be calculated as a weighted sum of all transmembrane currents in all cells located in the vicinity of the electrode. This computational scheme can considerably aid the modeling and analysis of MUA and LFP signals.Here, we describe LFPy, an open source Python package for numerical simulations of extracellular potentials. LFPy consists of a set of easy-to-use classes for defining cells, synapses and recording electrodes as Python objects, implementing this biophysical modeling scheme. It runs on top of the widely used NEURON simulation environment, which allows for flexible usage of both new and existing cell models.Further, calculation of extracellular potentials using the line-source-method is efficiently implemented.We describe the theoretical framework underlying the extracellular potential calculations and illustrate by examples how LFPy can be used both for simulating LFPs, i.e., synaptic contributions from single cells as well a populations of cells, and MUAs, i.e., extracellular signatures of action potentials.

  10. LFPy: a tool for biophysical simulation of extracellular potentials generated by detailed model neurons.

    Science.gov (United States)

    Lindén, Henrik; Hagen, Espen; Lęski, Szymon; Norheim, Eivind S; Pettersen, Klas H; Einevoll, Gaute T

    2013-01-01

    Electrical extracellular recordings, i.e., recordings of the electrical potentials in the extracellular medium between cells, have been a main work-horse in electrophysiology for almost a century. The high-frequency part of the signal (≳500 Hz), i.e., the multi-unit activity (MUA), contains information about the firing of action potentials in surrounding neurons, while the low-frequency part, the local field potential (LFP), contains information about how these neurons integrate synaptic inputs. As the recorded extracellular signals arise from multiple neural processes, their interpretation is typically ambiguous and difficult. Fortunately, a precise biophysical modeling scheme linking activity at the cellular level and the recorded signal has been established: the extracellular potential can be calculated as a weighted sum of all transmembrane currents in all cells located in the vicinity of the electrode. This computational scheme can considerably aid the modeling and analysis of MUA and LFP signals. Here, we describe LFPy, an open source Python package for numerical simulations of extracellular potentials. LFPy consists of a set of easy-to-use classes for defining cells, synapses and recording electrodes as Python objects, implementing this biophysical modeling scheme. It runs on top of the widely used NEURON simulation environment, which allows for flexible usage of both new and existing cell models. Further, calculation of extracellular potentials using the line-source-method is efficiently implemented. We describe the theoretical framework underlying the extracellular potential calculations and illustrate by examples how LFPy can be used both for simulating LFPs, i.e., synaptic contributions from single cells as well a populations of cells, and MUAs, i.e., extracellular signatures of action potentials.

  11. Normalization: A Preprocessing Stage

    OpenAIRE

    Patro, S. Gopal Krishna; Sahu, Kishore Kumar

    2015-01-01

    As we know that the normalization is a pre-processing stage of any type problem statement. Especially normalization takes important role in the field of soft computing, cloud computing etc. for manipulation of data like scale down or scale up the range of data before it becomes used for further stage. There are so many normalization techniques are there namely Min-Max normalization, Z-score normalization and Decimal scaling normalization. So by referring these normalization techniques we are ...

  12. Normal and seasonally amplified indoor radon levels

    International Nuclear Information System (INIS)

    Gammage, R.B.; Dudney, C.S.; Wilson, D.L.; King, D.

    1995-01-01

    Winter and summer indoor radon measurements are reported for 121 houses in Freehold, New Jersey. When presented as winter:summer ratios of indoor radon, the data closely approximate a lognormal distribution. The geometric mean is 1.49. Freehold is located on the fairly flat coastal plain. The winter:summer ratios are believed to represent the norm for regions of the U.S. with cold winters and hot summers. The Freehold data set can be compared to corresponding data sets from other locations to suggest seasonal perturbations of indoor radon arising from unusual causes

  13. The extracellular domain of neurotrophin receptor p75 as a candidate biomarker for amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Stephanie R Shepheard

    Full Text Available Objective biomarkers for amyotrophic lateral sclerosis would facilitate the discovery of new treatments. The common neurotrophin receptor p75 is up regulated and the extracellular domain cleaved from injured neurons and peripheral glia in amyotrophic lateral sclerosis. We have tested the hypothesis that urinary levels of extracellular neurotrophin receptor p75 serve as a biomarker for both human motor amyotrophic lateral sclerosis and the SOD1(G93A mouse model of the disease. The extracellular domain of neurotrophin receptor p75 was identified in the urine of amyotrophic lateral sclerosis patients by an immuno-precipitation/western blot procedure and confirmed by mass spectrometry. An ELISA was established to measure urinary extracellular neurotrophin receptor p75. The mean value for urinary extracellular neurotrophin receptor p75 from 28 amyotrophic lateral sclerosis patients measured by ELISA was 7.9±0.5 ng/mg creatinine and this was significantly higher (p<0.001 than 12 controls (2.6±0.2 ng/mg creatinine and 19 patients with other neurological disease (Parkinson's disease and Multiple Sclerosis; 4.1±0.2 ng/mg creatinine. Pilot data of disease progression rates in 14 MND patients indicates that p75NTR(ECD levels were significantly higher (p = 0.0041 in 7 rapidly progressing patients as compared to 7 with slowly progressing disease. Extracellular neurotrophin receptor p75 was also readily detected in SOD1(G93A mice by immuno-precipitation/western blot before the onset of clinical symptoms. These findings indicate a significant relation between urinary extracellular neurotrophin receptor p75 levels and disease progression and suggests that it may be a useful marker of disease activity and progression in amyotrophic lateral sclerosis.

  14. Decreased extracellular pH inhibits osteogenesis through proton-sensing GPR4-mediated suppression of yes-associated protein.

    Science.gov (United States)

    Tao, Shi-Cong; Gao, You-Shui; Zhu, Hong-Yi; Yin, Jun-Hui; Chen, Yi-Xuan; Zhang, Yue-Lei; Guo, Shang-Chun; Zhang, Chang-Qing

    2016-06-03

    The pH of extracellular fluids is a basic property of the tissue microenvironment and is normally maintained at 7.40 ± 0.05 in humans. Many pathological circumstances, such as ischemia, inflammation, and tumorigenesis, result in the reduction of extracellular pH in the affected tissues. In this study, we reported that the osteogenic differentiation of BMSCs was significantly inhibited by decreases in the extracellular pH. Moreover, we demonstrated that proton-sensing GPR4 signaling mediated the proton-induced inhibitory effects on the osteogenesis of BMSCs. Additionally, we found that YAP was the downstream effector of GPR4 signaling. Our findings revealed that the extracellular pH modulates the osteogenic responses of BMSCs by regulating the proton-sensing GPR4-YAP pathway.

  15. Albumin-induced apoptosis of glomerular parietal epithelial cells is modulated by extracellular signal-regulated kinase 1/2

    Science.gov (United States)

    Ohse, Takamoto; Krofft, Ron D.; Wu, Jimmy S.; Eddy, Allison A.; Pippin, Jeffrey W.; Shankland, Stuart J.

    2012-01-01

    Background. The biological role(s) of glomerular parietal epithelial cells (PECs) is not fully understood in health or disease. Given its location, PECs are constantly exposed to low levels of filtered albumin, which is increased in nephrotic states. We tested the hypothesis that PECs internalize albumin and increased uptake results in apoptosis. Methods. Confocal microscopy of immunofluorescent staining and immunohistochemistry were used to demonstrate albumin internalization in PECs and to quantitate albumin uptake in normal mice and rats as well as experimental models of membranous nephropathy, minimal change disease/focal segmental glomerulosclerosis and protein overload nephropathy. Fluorescence-activated cell sorting analysis was performed on immortalized cultured PECs exposed to fluorescein isothiocyanate (FITC)-labeled albumin in the presence of an endosomal inhibitor or vehicle. Apoptosis was measured by Hoechst staining in cultured PECs exposed to bovine serum albumin. Levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) were restored by retroviral infection of mitogen-activated protein kinase (MEK) 1/2 and reduced by U0126 in PECs exposed to high albumin levels in culture and apoptosis measured by Hoechst staining. Results. PECs internalized albumin normally, and this was markedly increased in all of the experimental disease models (P PECs also internalize FITC-labeled albumin, which was reduced by endosomal inhibition. A consequence of increased albumin internalization was PEC apoptosis in vitro and in vivo. Candidate signaling pathways underlying these events were examined. Data showed markedly reduced levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (ERK1/2) in PECs exposed to high albumin levels in nephropathy and in culture. A role for ERK1/2 in limiting albumin-induced apoptosis was shown by restoring p-ERK1/2 by retroviral infection, which reduced apoptosis in cultured PECs, while a forced

  16. Extracellular nucleotide derivatives protect cardiomyctes against hypoxic stress

    DEFF Research Database (Denmark)

    Golan, O; Issan, Y; Isak, A

    2011-01-01

    assures cardioprotection. Treatment with extracellular nucleotides, or with tri/di-phosphate, administered under normoxic conditions or during hypoxic conditions, led to a decrease in reactive oxygen species production. CONCLUSIONS: Extracellular tri/di-phosphates are apparently the molecule responsible...

  17. The Role of Extracellular Matrix Quality in Pulmonary Fibrosis

    DEFF Research Database (Denmark)

    Kristensen, Jacob Hull; Karsdal, Morten Asser; Genovese, Federica

    2014-01-01

    This review discusses the role of extracellular matrix (ECM) quality in the pathogenesis of pulmonary fibrosis (PF). In PF, the highly ordered structure of collagens and elastin within the ECM of the lung is severely disrupted and lacks its original tissue quality. Discussions about the ECM have...... focused on the role of protein quantity in relation to the progression of PF, while the importance of lung ECM quality, defined by the levels of ECM protein modifications and by the protein distribution in lung tissue, has not been properly addressed. The quality and function of proteins may be altered...... by different post-translational modifications (PTMs), such as crosslinking, proteolytic cleavage, citrullination, misfolding and glycosylation. This paper is the first to review key data from the literature related to the lung ECM at the molecular level, relate these to changes observed at a macroscopic level...

  18. Biotechnological Aspects of Microbial Extracellular Electron Transfer

    Science.gov (United States)

    Kato, Souichiro

    2015-01-01

    Extracellular electron transfer (EET) is a type of microbial respiration that enables electron transfer between microbial cells and extracellular solid materials, including naturally-occurring metal compounds and artificial electrodes. Microorganisms harboring EET abilities have received considerable attention for their various biotechnological applications, in addition to their contribution to global energy and material cycles. In this review, current knowledge on microbial EET and its application to diverse biotechnologies, including the bioremediation of toxic metals, recovery of useful metals, biocorrosion, and microbial electrochemical systems (microbial fuel cells and microbial electrosynthesis), were introduced. Two potential biotechnologies based on microbial EET, namely the electrochemical control of microbial metabolism and electrochemical stimulation of microbial symbiotic reactions (electric syntrophy), were also discussed. PMID:26004795

  19. Methods to isolate extracellular vesicles for diagnosis

    Science.gov (United States)

    Kang, Hyejin; Kim, Jiyoon; Park, Jaesung

    2017-12-01

    Extracellular vesicles (EVs) are small membrane-bound bodies that are released into extracellular space by diverse cells, and are found in body fluids like blood, urine and saliva. EVs contain RNA, DNA and proteins, which can be biomarkers for diagnosis. EVs can be obtained by minimally-invasive biopsy, so they are useful in disease diagnosis. High yield and purity contribute to precise diagnosis of disease, but damaged EVs and impurities can cause confu sed results. However, EV isolation methods have different yields and purities. Furthermore, the isolation method that is most suitable to maximize EV recovery efficiency depends on the experimental conditions. This review focuses on merits and demerits of several types of EV isolation methods, and provides examples of how to diagnose disease by exploiting information obtained by analysis of EVs.

  20. Evaluation of aldosterone-and cortisol levels in blood plasma in normal conditions of ingestion of sodium and potassium, after saline-increase and depletion, in regard to position, and after stimulation with ACTH and angiotensin II

    International Nuclear Information System (INIS)

    Okada, H.

    1979-01-01

    Methods for the determination of plasma aldosterone and cortisol, by radioimmunoassay, were performed utilizing highly specific antisera. With this methodology it was possible to evaluate cortisol and aldosterone secretion, in six normal subjects, submitted to a basal rice diet on standing and recumbent positions, the effects of exogenous cortrosyn (β1-24 ACTH) and angiotensin II and the same manoevres with progressively increased Na + content of the diet. Aldosterone basal levels decreased with the increase of Na + content in the diet. However, there were no significant differences between the relative increments observed on the recumbent position, at the three levels of sodium intake. The relative increase of plasma aldosterone after ACTH was similar for each basal level of aldosterone induced by different sodium intakes. The responsiveness of aldosterone secretion to cortrosyn and standing position was similar, with no relation to the sodium intake. The infusion of angiotensin II induced an increase in plasma aldosterone, and the relative increment in the levels of the hormone were higher with high sodium than on the rice diet. The average basal cortisol value at the different levels of sodium intake was significantly different being greater on the basal, rice diet, and there was a decrease in cortisol level after recumbency, with the theree diets. The injection of ACTH induced similar cortisol secretion with no relation to the sodium intake. The infusion of non-hypertensive doses of angiotensin II resulted in an anomalous fall in cortisol level, probably because of 'shunt' of substrates to biosynthesis with the added effect of cortisol diurnal rhythmycity. (Author) [pt

  1. Stem cell extracellular vesicles and kidney injury

    OpenAIRE

    Grange, Cristina; Iampietro, Corinne; Bussolati, Benedetta

    2017-01-01

    Extracellular vesicles (EVs) appear as a new promising cell-free therapy for acute and chronic renal diseases. EVs retain characteristics of the cell of origin and those derived from stem cells may mimic their regenerative properties per se. In fact, EVs contain many active molecules such as proteins and RNA species that act on target cells through different mechanisms, stimulating proliferation and angiogenesis and reducing apoptosis and inflammation. There are several reports that demonstra...

  2. Extracellular matrix component signaling in cancer

    DEFF Research Database (Denmark)

    Multhaupt, Hinke A. B.; Leitinger, Birgit; Gullberg, Donald

    2016-01-01

    Cell responses to the extracellular matrix depend on specific signaling events. These are important from early development, through differentiation and tissue homeostasis, immune surveillance, and disease pathogenesis. Signaling not only regulates cell adhesion cytoskeletal organization and motil...... as well as matrix constitution and protein crosslinking. Here we summarize roles of the three major matrix receptor types, with emphasis on how they function in tumor progression. [on SciFinder(R)]...

  3. Existence of a soluble form of CD50 (intercellular adhesion molecule-3) produced upon human lymphocyte activation. Present in normal human serum and levels are increased in the serum of systemic lupus erythematosus patients.

    Science.gov (United States)

    Pino-Otín, M R; Viñas, O; de la Fuente, M A; Juan, M; Font, J; Torradeflot, M; Pallarés, L; Lozano, F; Alberola-Ila, J; Martorell, J

    1995-03-15

    CD50 (ICAM-3) is a leukocyte differentiation Ag expressed almost exclusively on hemopoietic cells, with a key role in the first steps of immune response. To develop a specific sandwich ELISA to detect a soluble CD50 form (sCD50), two different mAbs (140-11 and 101-1D2) recognizing non-overlapping epitopes were used. sCD50 was detected in the supernatant of stimulated PBMCs, with the highest levels after CD3 triggering. Simultaneously, the CD50 surface expression diminished during the first 24 h. sCD50 isolated from culture supernatant and analyzed by immunoblotting showed an apparent m.w. of 95 kDa, slightly smaller than the membrane form. These data, together with Northern blot kinetics analysis, suggest that sCD50 is cleaved from cell membrane. Furthermore, we detect sCD50 in normal human sera and higher levels in sera of systemic lupus erythematosus (SLE) patients, especially in those in active phase. The sCD50 levels showed a positive correlation with sCD27 levels (r = 0.4213; p = 0.0026). Detection of sCD50, both after in vitro CD3 triggering of PBMCs and increased in SLE sera, suggests that sCD50 could be used as a marker of lymphocyte stimulation.

  4. Extracellular proteases of Trichoderma species. A review.

    Science.gov (United States)

    Kredics, L; Antal, Zsuzsanna; Szekeres, A; Hatvani, L; Manczinger, L; Vágvölgyi, Cs; Nagy, Erzsébet

    2005-01-01

    Cellulolytic, xylanolytic, chitinolytic and beta-1,3-glucanolytic enzyme systems of species belonging to the filamentous fungal genus Trichoderma have been investigated in details and are well characterised. The ability of Trichoderma strains to produce extracellular proteases has also been known for a long time, however, the proteolytic enzyme system is relatively unknown in this genus. Fortunately, in the recent years more and more attention is focused on the research in this field. The role of Trichoderma proteases in the biological control of plant pathogenic fungi and nematodes has been demonstrated, and it is also suspected that they may be important for the competitive saprophytic ability of green mould isolates and may represent potential virulence factors of Trichoderma strains as emerging fungal pathogens of clinical importance. The aim of this review is to summarize the information available about the extracellular proteases of Trichoderma. Numerous studies are available about the extracellular proteolytic enzyme profiles of Trichoderma strains and about the effect of abiotic environmental factors on protease activities. A number of protease enzymes have been purified to homogeneity and some protease encoding genes have been cloned and characterized. These results will be reviewed and the role of Trichoderma proteases in biological control as well as their advantages and disadvantages in biotechnology will be discussed.

  5. Extracellular proteins: Novel key components of metal resistance in cyanobacteria?

    Directory of Open Access Journals (Sweden)

    Joaquin eGiner-Lamia

    2016-06-01

    Full Text Available Metals are essential for all living organisms and required for fundamental biochemical processes. However, when in excess, metals can turn into highly-toxic agents able to disrupt cell membranes, alter enzymatic activities and damage DNA. Metal concentrations are therefore tightly controlled inside cells, particularly in cyanobacteria. Cyanobacteria are ecologically relevant prokaryotes that perform oxygenic photosynthesis and can be found in many different marine and freshwater ecosystems, including environments contaminated with heavy metals. As their photosynthetic machinery imposes high demands for metals, homeostasis of these micronutrients has been widely studied in cyanobacteria. So far, most studies have focused on how cells are capable of controlling their internal metal pools, with a strong bias towards the analysis of intracellular processes. Ultrastructure, modulation of physiology, dynamic changes in transcription and protein levels have been studied, but what takes place in the extracellular environment when cells are exposed to an unbalanced metal availability remains largely unknown. The interest in studying the subset of proteins present in the extracellular space has only recently begun and the identification and functional analysis of the cyanobacterial exoproteomes are just emerging. Remarkably, metal-related proteins such as the copper-chaperone CopM or the iron-binding protein FutA2 have already been identified outside the cell. With this perspective, we aim to raise the awareness that metal-resistance mechanisms are not yet fully known and hope to motivate future studies assessing the role of extracellular proteins on bacterial metal homeostasis, with a special focus on cyanobacteria.

  6. Temporal Profiles Dissociate Regional Extracellular Ethanol versus Dopamine Concentrations

    Science.gov (United States)

    2015-01-01

    In vivo monitoring of dopamine via microdialysis has demonstrated that acute, systemic ethanol increases extracellular dopamine in regions innervated by dopaminergic neurons originating in the ventral tegmental area and substantia nigra. Simultaneous measurement of dialysate dopamine and ethanol allows comparison of the time courses of their extracellular concentrations. Early studies demonstrated dissociations between the time courses of brain ethanol concentrations and dopaminergic responses in the nucleus accumbens (NAc) elicited by acute ethanol administration. Both brain ethanol and extracellular dopamine levels peak during the first 5 min following systemic ethanol administration, but the dopamine response returns to baseline while brain ethanol concentrations remain elevated. Post hoc analyses examined ratios of the dopamine response (represented as a percent above baseline) to tissue concentrations of ethanol at different time points within the first 25–30 min in the